Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma.

Although Janus kinase (JAK) inhibitors have demonstrated efficacy for treating autoimmune disorders and myeloproliferative neoplasms, their efficacy in treating other types of cancer has not been clearly demonstrated. We evaluated oral ruxolitinib (15 mg twice daily) with oral methylprednisolone (40 mg every other day) for multiple myeloma (MM) patients with progressive disease who had received a proteasome inhibitor, lenalidomide, glucocorticosteroids and three or more prior regimens. All of the planned 29 patients had been enrolled with follow-up until 28 April 2022. Median lines of prior therapy were 6 (range 3-12). Cytogenetics and fluorescent in situ hybridization were evaluable in 28 patients; 9 (32%) and 17 (70%) patients showed high-risk cytogenetics and/or 1q+, respectively. The overall response rate was 31%. The median duration of response was 13.1 (range 2.8-22.0) months. Median progression-free survival rate was 3.4 (range 0.5-24.6) months, Overall, the treatment was well tolerated. The combination of ruxolitinib and methylprednisolone demonstrated significant clinical activity among previously heavily-treated MM patients, and responses were achieved among patients who had high-risk cytogenetics. This is the first clinical study to show activity of JAK inhibitors in combination with steroids for MM patients and expands the potential use of these drugs to those with cancers other than myeloproliferative neoplasms.

Fetal growth restriction and small for gestational age as predictors of neonatal morbidity: which growth nomogram to use?

BACKGROUND: Fetal growth nomograms were developed to screen for fetal growth restriction and guide clinical care to improve perinatal outcomes; however, existing literature remains inconclusive regarding which nomogram is the gold standard. OBJECTIVE: This study aimed to compare the ability of 4 commonly used nomograms (Hadlock, International Fetal and Newborn Growth Consortium for the 21st Century, Eunice Kennedy Shriver National Institute of Child Health and Human Development-unified standard, and World Health Organization fetal growth charts) and 1 institution-specific reference to predict small for gestational age and poor neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of all nonanomalous singleton pregnancies undergoing ultrasound at ≥20 weeks of gestation between 2013 and 2020 and delivering at a single academic center. Using random selection methods, the study sample was restricted to 1 pregnancy per patient and 1 ultrasound per pregnancy completed at ≥22 weeks of gestation. Fetal biometry data were used to calculate estimated fetal weight and percentiles according to the aforementioned 5 nomograms. Maternal and neonatal data were extracted from electronic medical records. Logistic regression was used to estimate the association between estimated fetal weight of <10th and <3rd percentiles compared with estimated fetal weight of 10th to 90th percentile as the reference group for small for gestational age and the neonatal composite outcomes (perinatal mortality, hypoxic-ischemic encephalopathy or seizures, respiratory morbidity, intraventricular hemorrhage, necrotizing enterocolitis, hyperbilirubinemia or hypoglycemia requiring neonatal intensive care unit admission, and retinopathy of prematurity). Receiver operating characteristic curve contrast estimation (primary analysis) and test characteristics were calculated for all nomograms and the prediction of small for gestational age and the neonatal composite outcomes. We restricted the sample to ultrasounds performed within 28 days of delivery; moreover, similar analyses were completed to assess the prediction of small for gestational age and neonatal composite outcomes. RESULTS: Among 10,045 participants, the proportion of fetuses classified as <10th percentile varied across nomograms from 4.9% to 9.7%. Fetuses with an estimated fetal weight of <10th percentile had an increased risk of small for gestational age (odds ratio, 9.9 [95% confidence interval, 8.5-11.5] to 12.8 [95% confidence interval, 10.9-15.0]). In addition, the estimated fetal weight of <10th and <3rd percentile was associated with increased risk of the neonatal composite outcome (odds ratio, 2.4 [95% confidence interval, 2.0-2.8] to 3.5 [95% confidence interval, 2.9-4.3] and 5.7 [95% confidence interval, 4.5-7.2] to 8.8 [95% confidence interval, 6.6-11.8], respectively). The prediction of small for gestational age with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 6.3 to 8.5 and an area under the curve of 0.62 to 0.67. Similarly, the prediction of the neonatal composite outcome with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 2.1 to 3.1 and an area under the curve of 0.55 to 0.57. When analyses were restricted to ultrasound within 4 weeks of delivery, among fetuses with an estimated fetal weight of <10th percentile, the risk of small for gestational age increased across all nomograms (odds ratio, 16.7 [95% confidence interval, 12.6-22.3] to 25.1 [95% confidence interval, 17.0-37.0]), and prediction improved (positive likelihood ratio, 8.3-15.0; area under the curve, 0.69-0.75). Similarly, the risk of neonatal composite outcome increased (odds ratio, 3.2 [95% confidence interval, 2.4-4.2] to 5.2 [95% confidence interval, 3.8-7.2]), and prediction marginally improved (positive likelihood ratio, 2.4-4.1; area under the curve, 0.60-0.62). Importantly, the risk of both being small for gestational age and having the neonatal composite outcome further increased (odds ratio, 21.4 [95% confidence interval, 13.6-33.6] to 28.7 (95% confidence interval, 18.6-44.3]), and the prediction of concurrent small for gestational age and neonatal composite outcome greatly improved (positive likelihood ratio, 6.0-10.0; area under the curve, 0.80-0.83). CONCLUSION: In this large cohort, Hadlock, recent fetal growth nomograms, and a local population-derived fetal growth reference performed comparably in the prediction of small for gestational age and neonatal composite outcomes.

Psychometric assessment of the US person-centered prenatal and maternity care scales in a low-income predominantly Latinx population in California.

OBJECTIVES: To assess psychometric properties of two scales developed to measure the quality of person-centered care during pregnancy and childbirth in the United States-the Person-Centered Prenatal Care (PCPC-US) and Person-Centered Maternity Care (PCMC-US) scales-in a low-income predominantly Latinx population in California. METHODS: Data were collected from July 2020 to June 2023 from surveys of low-income pregnant and birthing people in Fresno, California, participating in the "Engaging Mothers and Babies; Reimagining Antenatal Care for Everyone" (EMBRACE) trial. Research staff administered the 26-item PCPC-US scale at 30-34 weeks' gestation (n = 315) and the 35-item PCMC-US scale at 10-14 weeks after birth (n = 286), using the language preferred by the participant (English or Spanish). We assessed construct, criterion, and known group validity and internal consistency of the scales. RESULTS: 78% of respondents identified as Latinx. Factor analysis identified one dominant factor for each scale that accounted for over 60% of the cumulative variance, with most items loading at > 0.3. The items also loaded adequately on sub-scales for "dignity and respect," "communication and autonomy," and "responsive and supportive care." Cronbach's alpha for the full scales were > 0.9 and between 0.70 and 0.87 for the sub-scales. Summative scores range from 0 to 100, with higher scores indicating higher person-centered care. Correlations with scores on scales measuring prenatal care quality and birth experience provided evidence for criterion validity, while associations with known predictors provided evidence for known-group validity. CONCLUSIONS: The PCPC-US and PCMC-US scales, which were developed using a community-engaged process and found to have good psychometric properties in a largely high-income sample of Black women, were shown to also have good psychometric properties in a sample of low-income primarily Latinx women. Both scales provide valid and reliable tools to measure person-centered care experiences among minoritized communities to support efforts to reduce existing birth inequities.

"We All Want to Be Able to Tell You Something Hopeful": Clinicians' Experiences Providing Maternal-Fetal Surgery Counseling.

INTRODUCTION: Prenatal counseling about maternal-fetal surgery can be traumatic and confusing for pregnant people. It can also be technically and emotionally complex for clinicians. As maternal-fetal surgery rapidly advances and becomes more common, more evidence is needed to inform counseling practices. The objective of this study was to develop a deeper understanding of the methods clinicians currently use to train for and provide counseling, as well as their needs and recommendations for future education and training. METHODS: We used interpretive description methods and interviewed interprofessional clinicians who regularly counsel pregnant people about maternal-fetal surgery. RESULTS: We conducted 20 interviews with participants from 17 different sites who were maternal-fetal medicine specialists (30%), pediatric surgeons (30%), nurses (15%), social workers (10%), a genetic counselor (5%), a neonatologist (5%), and a pediatric subspecialist (5%). Most were female (70%), non-Hispanic white (90%), and practiced in the Midwest (50%). We identified four overarching themes: (1) contextualizing maternal-fetal surgery counseling; (2) establishing shared understanding; (3) supporting decision-making; and (4) training for maternal-fetal surgery counseling. Within these themes, we identified key practice differences among professions, specialties, institutions, and regions. CONCLUSION: Participants are committed to practicing informative and supportive counseling to empower pregnant people to make autonomous decisions about maternal-fetal surgery. Nevertheless, our findings indicate a dearth of evidence-based communication practices and guidance. Participants identified significant systemic limitations affecting pregnant people's decision-making options related to maternal-fetal surgery.

A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients.

Ruxolitinib with lenalidomide and dexamethasone shows anti-myeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma (MM) cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. A phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory (RR)MM who had been treated with lenalidomide, steroids and a proteasome inhibitor and showed progressive disease at study entry. A traditional 3 + 3 dose escalation design was used to enroll subjects in four cohorts. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1-21 of a 28 day cycle and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR) and overall response rate (ORR). Forty-nine patients were enrolled. The median age was 64 years and they had received a median of six prior treatments including lenalidomide and steroids to which 94% were refractory. No dose limiting toxicities occurred. The CBR and ORR were 49% and 36%, respectively. All responding patients were refractory to lenalidomide. Grade 3 or 4 adverse events (AEs) included anemia (17%), decreased lymphocyte count (15%), and hypophosphatemia (10%). Most common serious AEs included sepsis (9.8%) and pneumonia (7.8%). This Phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating MM. NCT03110822.

Rapid Deployment of a Mobile Medical Clinic During the COVID-19 Pandemic: Assessment of Dyadic Maternal-Child Care.

OBJECTIVES: To describe demographic characteristics and health-related social needs of families who accessed maternal-infant care through a mobile medical clinic (MMC) during the COVID-19 pandemic and to explore feasibility, acceptability, perceived benefits, and barriers to care. METHODS: In this mixed-methods observational study, chart reviews, telephone surveys, and qualitative interviews in English and Spanish were conducted with caregivers who accessed the MMC between April and November 2020. Qualitative interviews were analyzed with the constant comparative method alongside descriptive chart and survey data analyses. RESULTS: Of 139 caregiver-infant dyads contacted, 68 (48.9%) completed the survey; 27 also completed the qualitative interview. The survey participants did not differ from the larger sample; most (86.7%) were people of color (52.9% identified as Latino and 33.8% as Black). Health-related social needs were high, including food insecurity (52.9%), diaper insecurity (44.1%), and anxiety (32%). Four women (6.1%) were diagnosed with hypertension requiring urgent evaluation. Nearly all (98.5%) reported being very satisfied with the services. Major themes from qualitative interviews included (1) perceived patient- and family-centered care, (2) perceived safety, and (3) perceived benefits of dyadic mother-infant care. CONCLUSIONS FOR PRACTICE: In this assessment of caregivers who accessed the MMC-a rapidly-developed COVID-19 pandemic response-insights from caregivers, predominantly people of color, provided considerations for future postpartum/postnatal service delivery. Perceptions that the MMC addressed health-related social needs and barriers to traditional office-based visits and the identification of maternal hypertension requiring urgent intervention suggest that innovative models for postpartum mother-infant care may have long-lasting benefits.

Does Antenatal Progesterone Administration Modify the Risk of Neonatal Intraventricular Hemorrhage?

OBJECTIVE: Progesterone administration has been associated with improved neurological outcomes following traumatic brain injury in adults. However, studies examining the effect of progesterone on the risk of neonatal intraventricular hemorrhage (IVH) are inconsistent. We sought to determine if maternal administration of intramuscular 17-α-hydroxyprogesterone caproate (17-OHPC) is associated with decreased rates of IVH in infants born before 32-weeks gestation. STUDY DESIGN: This is a retrospective study of liveborn singleton deliveries between 20- and 32-weeks gestation at two large academic medical centers from January 1, 2012 to August 30, 2020. Data were extracted from hospital electronic medical record data warehouses using standardized definitions and billing and diagnosis codes. We evaluated receipt of 17-OHPC in the antepartum period and diagnosis of IVH (grade I-IV, per Volpe classification) during the neonatal delivery hospitalization encounter. Bivariate and multivariate analyses were performed to examine the association between 17-OHPC and neonatal IVH adjusting for potential confounders. Odds ratio (ORs) and 95% confidence intervals (CIs) were presented. RESULTS: Among 749 neonates born between 20- and 32-week gestation, 140 (18.7%) of their mothers had received antenatal 17-OHPC and 148 (19.8%) were diagnosed with IVH after birth. No significant association was observed between maternal 17-OHPC and neonatal IVH in unadjusted (OR 1.14, 95% CI 0.72-1.78) or adjusted analyses (adjusted odds ratio 1.14, 95% CI 0.71-1.84). Independent of exposure to 17-OHPC, as expected, infants born <28-weeks gestation or those with very low birthweight (<1,500 g) were at an increased risk of IVH (OR 2.32, 95% CI 1.55-3.48 and OR 2.19, 95% CI 1.09-4.38, respectively). CONCLUSION: Antenatal maternal 17-OHPC administration was not associated with the risk of neonatal IVH. Further research may be warranted to determine whether timing, route of delivery, and duration of progesterone therapy impact rates of neonatal IVH. KEY POINTS: · This study aimed to compare the frequency of intraventricular hemorrhage in preterm neonates exposed to antenatal 17-α-hydroxyprogesterone caproate to those not exposed.. · In neonates born at <32-weeks gestation, maternal use of progesterone is not associated with the risk of intraventricular hemorrhage.. · In contrast to preclinical and adult data, this study suggests that progesterone exposure is not associated with the prevention of neonatal brain injury..

Measurement of Marginal Placental Cord Insertion by Prenatal Ultrasound Was Found Not to Be Predictive of Adverse Perinatal Outcomes.

OBJECTIVES: The clinical importance of marginal cord insertion (MCI) is currently controversial. In this study, we examined the association between MCI and adverse perinatal outcomes. We also evaluated the ultrasound-measured distance from the site of placental cord insertion (PCI) to the placental margin (PCI distance) and perinatal outcomes. METHODS: This was a retrospective cohort study of MCI and control pregnancies presenting to a single institution between September 2014 and August 2016. Marginal cord insertion was diagnosed on routine anatomy ultrasound scans at 20 weeks' gestation. The primary outcome was fetal intolerance to labor. Secondary outcomes of interest included mode of delivery, gestational age at delivery, Apgar scores at 1 and 5 minutes, birth weight, delivery complications, and neonatal intensive care unit admission. The PCI distance was determined by an ultrasound review. Statistical significance was evaluated by a χ2 analysis, descriptive statistics, Wilcoxon tests, and regression models with log-transformed outcomes, the PCI distance, or both as needed. RESULTS: Of 675 abnormal cord insertion cases, we identified 183 that met inclusion criteria. We found no statistically significant association between MCI and fetal intolerance to labor (odds ratio, 1.24 [95% confidence interval, 0.55-2.80]; P = .71) or secondary outcomes. Furthermore, we found no significant correlation between perinatal outcomes and the PCI distance. CONCLUSIONS: Our study suggests that MCI pregnancies, regardless of the specific PCI distance, might not be at increased risk of adverse perinatal outcomes. This finding questions the need for heightened antepartum surveillance of this patient population.

Laparoscopic Ligation of Uterine Vasculature for Fertility-Sparing Management of Postabortal Hemorrhage.

STUDY OBJECTIVE: To present a surgical video in which bilateral uterine vasculature was ligated laparoscopically in order to preserve the uterus in a patient with postabortal hemorrhage. DESIGN: A case report (Canadian Task Force classification III). SETTING: A tertiary referral center in New Haven, CT. INTERVENTIONS: This is a step-by-step demonstration of laparoscopic ligation of the uterine vasculature in a patient with postabortal hemorrhage. The patient was a 33-year-old Para 4014 woman who presented with postabortal hemorrhage after she underwent an urgent dilation and evacuation for the management of symptomatic placenta accreta at 19 weeks of pregnancy. The patient underwent a physical examination when she presented to the emergency department with postabortal hemorrhage. She was hemodynamically stable, and the examination was negative for cervical or vaginal lacerations. Coagulation studies were negative for any coagulopathy. A pelvic ultrasound did not show any retained products of conception. As per the Society of Family Planning guidelines, uterine massage was performed, and uterotonics (i.e., methylergonovine maleate 0.2 mg intramuscularly and misoprostol 1000 mg per rectum) were given [1]. The postabortal hemorrhage persisted despite medical therapy with an approximate blood loss of 600 mL over 2 hours. An intrauterine tamponade balloon was placed, and the patient then underwent a uterine angiogram and bilateral uterine artery embolization secondary to continued vaginal bleeding despite medical management. She was closely monitored and noted to have another 500 mL of blood loss over 2 hours after completion of uterine artery embolization. At this point, she was resuscitated with 2 U red blood cells because she developed symptoms of hemodynamic instability. Her hematocrit was increased suboptimally after transfusion with stabilization of her vitals. The patient was then counseled on her surgical options because she had failed medical management, intrauterine balloon tamponade, and uterine artery embolization. She stated a strong desire to preserve her uterus. Given her overall hemodynamic stability, laparoscopic ligation of the uterine vessels was proposed, which she agreed on [2]. Risks of the laparoscopic approach were explained to the patient, which included injury to the uterus, ureters, blood vessels, and nerves as well as the possibility of conversion to laparotomy. The surgery started with exploration of the peritoneal cavity. Her uterus was noted to be significantly enlarged with many engorged vessels. In order to decrease the risk of uterine perforation in this bulky and highly vascular uterus, the surgeon decided not to place a uterine manipulator. The retroperitoneum was entered at the right pelvic sidewall. Pararectal and paravesical spaces were then developed. Ureterolysis was performed in order to free its peritoneal and uterine artery attachments. The uterine artery was skeletonized cephalad to the hypogastric bifurcation and was ligated with 5-mm vascular clips. The attention was then turned to the ovarian vessels at the cornu of the uterus. Peritoneal avascular windows were created inferior and superior to the vessels. The blood supply was then ligated with an absorbable suture, and the ligature was secured using the extracorporeal knot tying technique. The same steps were repeated on the left pelvic sidewall. The procedure was completed once excellent hemostasis was assured. Besides the technical steps of the procedure, pelvic anatomic landmarks have also been emphasized in this video for educational purposes. MEASUREMENTS AND MAIN RESULTS: Laparoscopic ligation of the uterine vasculature was performed without any complications. The operative time was 65 minutes, and blood loss was minimal. The patient had an uneventful postoperative course and was discharged home the day after her laparoscopic surgery. CONCLUSION: The uterus was preserved with this minimally invasive approach for the management of postabortal hemorrhage. Laparoscopic ligation of the uterine vessels should be considered in hemodynamically stable patients who desire future fertility when managing postabortal hemorrhage.

"I don't have a telephone to the fetus": Clinicians' conceptions of fetal patienthood in maternal-fetal surgery counseling.

RATIONALE: Maternal fetal surgery (MFS) has developed rapidly since the 1960s and centers for fetal diagnosis and therapy (CFDT) have proliferated. As a result, CFDT clinicians have intervened with fetuses through pregnant bodies for decades, yet the patienthood status of the fetus and its implications for the pregnant person's autonomy have been relatively unexamined. OBJECTIVE: Our overall research aims were threefold: (1) to explore how clinicians train for and provide counseling for MFS; (2) to examine how clinicians assess fetal patienthood and its implications; and (3) to understand clinicians' professed needs and their recommendations for education and training for the provision of MFS counseling. This focuses on aim two. METHOD: In this qualitative study, conducted using in-depth interviews, we examined how 20 clinicians from 17 different sites understood fetal patienthood, how that affected their counseling of pregnant patients, and whether they drew on extant ethical frameworks for guidelines. RESULTS: We identified three major themes: 1) Clinicians entered fetal surgery consultations with assumptions about fetal patienthood (frequently informed by beliefs about fetal viability, maternal attachment, and disciplinary perspectives); 2) they consciously assessed their pregnant patients' connections to their fetus to inform or re-calibrate their own understandings of fetal patienthood; and 3) they used a threshold -based conceptualization whereby the fetus achieved patienthood after crossing a symbolic boundary, often related to the clinician's ability to intervene. CONCLUSIONS: Few clinicians invoked an extant ethical framework to determine fetal patienthood; most asserted that they did not view directive counseling toward MFS as appropriate, instead working diligently to protect pregnant patients' autonomy and rights to self-determination.

Cell-free fetal DNA impairs trophoblast migration in a TLR9-dependent manner and can be reversed by hydroxychloroquine.

Growing evidence suggests a relationship between elevated circulating placental-derived cell-free fetal DNA (cffDNA) and preeclampsia. Hypomethylation of CpG motifs, a hallmark of cffDNA, allows it to activate Toll-like receptor 9 (TLR9). Using an in vitro human first trimester extravillous trophoblast cell model, we sought to determine if trophoblast-derived cffDNA and ODN 2216, a synthetic unmethylated CpG oligodeoxynucleotide, directly impacted spontaneous trophoblast migration. The role of the DNA sensors TLR9, AIM2, and cGAS was assessed using the inhibitor A151. To test whether any effects could be reversed by therapeutic agents, trophoblasts were treated with or without cffDNA or ODN 2216 with or without aspirin (ASA; a known cGAS inhibitor), aspirin-triggered lipoxin (ATL), or hydroxychloroquine (HCQ; a known TLR9 inhibitor). Trophoblast-derived cffDNA and ODN 2216 reduced trophoblast migration without affecting cell viability. Reduced trophoblast migration in response to cffDNA or ODN 2216 was reversed by A151. cffDNA inhibition of trophoblast migration was reversed by HCQ, while ASA or ATL had no effect. In contrast ODN 2216 inhibition of trophoblast migration was reversed by ASA, ATL and HCQ. Our findings suggest that cffDNA can exert a local effect on placental function by impairing trophoblast migration through activation of innate immune DNA sensors. HCQ, a known TLR9 inhibitor, reversed the effects of cffDNA on trophoblast migration. Greater insights into the molecular underpinnings of how cffDNA impacts placentation can aid in our understanding of the pathogenesis of preeclampsia, and in the development of novel therapeutic approaches for preeclampsia therapy.

Using a Patient Educational Video to Improve Knowledge of Maternal Mortality Warning Signs: A Randomized Controlled Trial.

OBJECTIVE: To determine whether a community-informed, language-concordant postpartum video education campaign, developed with community input, improves patients' knowledge of warning signs for postpartum maternal mortality (infection, hemorrhage, hypertensive disorders, and postpartum depression) compared with routine discharge procedures. METHODS: A single-center, investigator-blinded, parallel-group randomized controlled trial of postpartum individuals who delivered at a large, urban, tertiary care hospital. Eligible participants were enrolled and completed a baseline knowledge questionnaire. After delivery, they were randomized to routine discharge education (control) or routine education plus video education (intervention). After discharge education, patient knowledge was again assessed in both groups before participants left the hospital. The primary outcome was the percentage of participants who showed improvement in their knowledge, measured by the number of correct questionnaire responses after education compared with their baseline, assessed as a binary outcome. A sample size of 150 (75 per group) was planned to detect a 25% absolute increase in the frequency of the primary outcome. RESULTS: From July to August 2022, 296 participants were screened and 200 were randomized (100 per group). Eighty-two percent of participants had college or graduate education, and 71.5% had commercial insurance. There was no significant difference in baseline characteristics. There was no statistically significant difference in the percentage of participants who improved their scores between the baseline and posteducation questionnaires (64.5% vs 50.0%, P =.09). However, the median posteducation questionnaire total score was significantly higher in the video education group (14 [interquartile range 12-15] vs 13 [interquartile range 12-14], P =.003). In addition, they more frequently reported that video education was "very helpful" (83.9% vs 72.5%, P =.23) and that they were "very satisfied" with their education (86.1% vs 75.5%, P =.29). CONCLUSION: Enhanced postpartum education through a novel video did not result in a statistically significant difference in frequency of improved score on the posteducation questionnaires but was associated with increased satisfaction with care. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05159726.

Severe Maternal Morbidity Review and Preventability Assessment in a Large Academic Center.

With the goal of identifying factors contributing to severe maternal morbidity (SMM) at our institution, we established a formal SMM review process. We performed a retrospective cohort study including all SMM cases as defined by American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine consensus criteria that were managed at Yale-New Haven Hospital over a 4-year period. Overall, 156 cases were reviewed. The SMM rate was 0.49% (95% CI 0.40-0.58). The leading causes of SMM were hemorrhage (44.9%) and nonintrauterine infection (14.1%). Two thirds of the cases were deemed to be preventable. Preventability was mostly associated with health care professional-level (79.4%) and system-level (58.8%) factors that could coexist. Detailed case review allowed for identification of preventable causes of SMM, revealed gaps in care, and allowed for implementation of practice changes targeting health care professional-level and system-level factors.

A phase 2 trial of the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone for high-risk relapsed/refractory multiple myeloma.

High-risk multiple myeloma (MM) continues to have a poor prognosis and remains a therapeutic challenge. This phase 2 study evaluated the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib, and low-dose dexamethasone for patients with high-risk relapsed/refractory (RR)MM (NCT03104270). Of 13 enrolled patients, 11 were evaluable for efficacy. Overall response rate and clinical benefit rate were 45.4% and 54.5%, respectively. Deep responses were observed including two complete responses. The novel quadruplet combination was overall well-tolerated, with clinically manageable adverse events. Common adverse events of ≥ grade 3 included lymphopenia (15%), anemia (15%), sepsis (15%), pneumonia (15%), and hypophosphatemia (15%). The novel combination showed promising efficacy and was well tolerated in this heavily pretreated MM population. Even though the study was terminated early prior to completion of enrollment, the results indicate that this may be a promising therapeutic approach for high-risk RRMM patients, which warrants further study.

One-anastomosis gastric bypass (OAGB) in patients with BMI < 30 kg/m2 and diabetes mellitus type 2 (DM2).

INTRODUCTION: Introduction: type-2 diabetes mellitus (DM2) is a major health problem, as it leads to increased morbidity and mortality. Metabolic surgery has shown good results in glycemic control; however, its use has not become popular. Objectives: to evaluate DM2 remission, as well as changes in body mass index (BMI), in overweight diabetic patients after undergoing metabolic surgery. Methods: a retrospective review was carried out of all patients with DM2 and BMI between 25 and 29.9 kg/m2 who underwent laparoscopic one-anastomosis gastric bypass (OAGB) as metabolic procedure between 2016 and 2019. Results: a total of 15 patients were included with a mean age of 46.6 ± 11.25 years. Mean BMI was 28.41 ± 0.94 kg/m2. Average duration was 5.4 ± 2.79 years, and presurgical fasting glucose was 288.53 ± 65.22 mg/dL. Preoperative glycated hemoglobin (HbA1c) was 9.58 ± 1.66 %. Two years after surgery HbA1c was 5.21 ± 0.26 %. The remission rate of DM2 was 100 %. All patients maintained a normal BMI range. Conclusions: OAGB is a valid alternative for complete DM2 remission no matter if it is not accompanied by some degree of obesity, since in this case the length of the biliopancreatic limb and common channel is modified to make a less malabsorptive procedure.

INTRODUCCIÓN: Introducción: la diabetes mellitus de tipo 2 (DM2) es un gran problema de salud ya que conlleva un aumento de la morbimortalidad. La cirugía metábolica ha demostrado tener buenos resultados en el control glucémico; sin embargo, su uso no se ha popularizado. Objetivos: evaluar la remisión de la DM2, así como los cambios en el índice de masa corporal (IMC), en pacientes diabéticos con sobrepeso despúes de realizarse una cirugía metabólica. Métodos: se realizó una revisión retrospectiva de todos los pacientes con DM2 e IMC entre 25 y 29,9 kg/m2 que fueron sometidos a bypass gástrico de una sola anastomosis (BAGUA) laparoscópico como procedimiento metabólico entre 2016 y 2019. Resultados: se incluyó un total de 15 pacientes con una edad media de 46,6 ± 11,25 años. El IMC medio fue de 28,41 ± 0,94 kg/m2. La media de evolución fue de 5,4 ± 2,79 años y la glucosa en ayunas prequirúgica de 288,53 ± 65,22 mg/dL. La hemoglobina glucosilada (HbA1c) preoperatoria fue del 9,58 ± 1,66 %. A los 2 años después de la cirugía, la HbA1c fue del 5,21 ± 0,26 %. La tasa de remisión de la DM2 fue del 100 %. Todos los pacientes se mantuvienron en un rango normal de IMC. Conclusiones: el BAGUA es una alternativa eficaz para la remisión completa de la DM2 sin importar que no se acompañe de algun grado obesidad, ya que en este caso se modifica la longitud del asa biliopancreática y el canal común para hacer un procedimiento menos malabsortivo.

Resolution of abdominal hernia with loss of home in two surgical times, in a patient with morbid obesity.

Obesity is a risk factor for the development of anterior abdominal wall hernias. Incisional hernias develop in up to 13% of laparotomies: the most difficult to repair are complex and multiple recurrent hernias with significant loss of control. The best approach to treating obese patients who concomitantly have hernias of the anterior abdominal wall is still a matter of debate. We present a clinical case of a patient with morbid obesity and abdominal hernia with loss of residence, who underwent bariatric surgery before ventral plasty.

La obesidad es un factor de riesgo para el desarrollo de hernias de la pared abdominal anterior. Las hernias incisionales se desarrollan hasta en el 13% de las laparotomías. Las más difíciles de reparar son las hernias recurrentes complejas y múltiples con pérdida significativa de domicilio. El mejor enfoque en el tratamiento de pacientes obesos y que concomitantemente tienen hernias de la pared abdominal anterior es aún un tema de debate. Presentamos el caso clínico de un paciente con obesidad mórbida y hernia abdominal con pérdida de domicilio, intervenido de cirugía bariatrica antes de la plastia ventral.

Trisomy 21 is Associated with Caspase-2 Upregulation in Cytotrophoblasts at the Maternal-Fetal Interface.

Impaired placentation is implicated in poor perinatal outcomes associated with Trisomy 21. Earlier studies revealed abnormal cytotrophoblast differentiation along the invasive pathway as a contributing mechanism. To further elucidate the causes, we evaluated Caspase-2 expression at the protein level (immunolocalization and immunoblot) in samples from Trisomy 21 (n = 9) and euploid (n = 4) age-matched placentas. Apoptosis was investigated via the TUNEL assay. An immunolocalization approach was used to characterize Caspase-3, Fas (CD95), and Fas ligand in the same samples. Caspase-2 was significantly overexpressed in Trisomy 21 placentas, with the highest expression in villous cores and invasive cytotrophoblasts. Immunolocalization showed that Caspase-3 had a similar expression pattern as Caspase-2. Using the TUNEL approach, we observed high variability in the number of apoptotic cells in biopsies from different regions of the same placenta and among different placentas. However, Trisomy 21 placentas had more apoptotic cells, specifically in cell columns and basal plates. Furthermore, Caspase-2 co-immunolocalized with Fas (CD95) and FasL in TUNEL-positive extravillous cytotrophoblasts, but not in villous cores. These results help explain the higher levels of apoptosis among placental cells of Trisomy 21 pregnancies in molecular terms. Specifically, the co-expression of Caspase-2 and Caspase-3 with other regulators of the apoptotic process in TUNEL-positive cells suggests these molecules may cooperate in launching the observed apoptosis. Among trophoblasts, only the invasive subpopulation showed this pattern, which could help explain the higher rates of adverse outcomes in these pregnancies. In future experiments, this relationship will be further examined at a functional level in cultured human trophoblasts.

A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma.

PURPOSE: Ruxolitinib with lenalidomide and dexamethasone shows antimyeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. Therefore, a phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory multiple myeloma (RRMM) who had been treated with lenalidomide/steroids and a proteasome inhibitor and showed progressive disease at study entry. PATIENTS AND METHODS: A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts with planned total enrollment of 28 patients. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1-21 of a 28-day cycle, and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR), and overall response rate (ORR). RESULTS: Twenty-eight patients were enrolled. The median age was 67 years and received a median of six prior treatments including lenalidomide and steroids to which 93% were refractory. No dose-limiting toxicities occurred. The CBR and ORR were 46% and 38%, respectively. All 12 responding patients were refractory to lenalidomide. Grade 3 or grade 4 adverse events (AE) included anemia (18%), thrombocytopenia (14%), and lymphopenia (14%). Most common serious AEs included sepsis (11%) and pneumonia (11%). CONCLUSIONS: This phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating multiple myeloma (ClinicalTrials.gov number, NCT03110822).

Impacts of glyphosate-based herbicides on disease resistance and health of crops: a review.

Based on experimental data from laboratory and field, numerous authors have raised concern that exposure to glyphosate-based herbicides (GBHs) may pre-dispose crops to damage by microbial pathogens. In this review, we distinguish and evaluate two principal pathways by which GBHs may affect the susceptibility of crops to disease: pathway 1-via disruptions to rhizosphere microbial ecology, and pathway 2-via restriction of nutrients to crops. We conclude that GBHs have the potential to undermine crop health in a number of ways, including: (i) impairment of the innate physiological defences of glyphosate-sensitive (GS) cultivars by interruption of the shikimic acid pathway; (ii) impairment of physiological disease defences has also been shown to occur in some glyphosate-resistant (GR) cultivars, despite their engineered resistance to glyphosate's primary mode of action; (iii) interference with rhizosphere microbial ecology (in particular, GBHs have the potential to enhance the population and/or virulence of some phytopathogenic microbial species in the crop rhizosphere); and finally, (iv) the as yet incompletely elucidated reduction in the uptake and utilisation of nutrient metals by crops. Future progress will best be achieved when growers, regulators and industry collaborate to develop products, practices and policies that minimise the use of herbicides as far as possible and maximise their effectiveness when used, while facilitating optimised food production and security.

La hipertensión arterial en animales de laboratorio / High blood pressure in experimental animals

Las Ciencias Médicas y Biológicas requieren, prioritariamente, que la investigación y la experimentación sean desarrolladas sobre organismos completos (los modelos animales). Su utilización ha permitido desarrollar innumerables ensayos preclínicos para evaluar los mecanismos patógenos y terapéuticos de diversas enfermedades, así como el estudio de las causas, naturaleza y cura de múltiples desórdenes de la salud humana. En este trabajo se muestra una panorámica general de los biomodelos de hipertensión arterial donde se describen: conceptos, características, origen, importancia, utilidad y procedimientos experimentales durante su fase de inducción. También se pondera la justificación de los biomodelos empleados en los estudios preclínicos de esta enfermedad. De igual forma, se describen los antecedentes para medir las alteraciones, las técnicas y los métodos directos e indirectos de medición de la presión arterial, la cual fue provocada experimentalmente en los animales de laboratorio para realizar los estudios de hipertensión humana.

Medical and biological sciences require, as a priority, that research and experimentation be carried out on complete organisms (animal models). Its use has allowed the development of innumerable preclinical tests to evaluate pathogenic and therapeutic mechanisms of various diseases, as well as to study the causes, nature and cure of multiple human health disorders. In this work, we show a general overview of arterial hypertension biomodels where concepts, characteristics, origin, importance, utility and experimental procedures during their induction phase are described. The justification of the biomodels used in preclinical studies of this disease is also considered. Antecedents are also described to measure alterations, techniques and direct and indirect methods of measurement of arterial pressure, which was provoked experimentally in the laboratory animals to carry out the studies of human hypertension.