Impact of isolation method on cellular activation and presence of specific tendon cell subpopulations during in vitro culture.

Tendon injuries are common and heal poorly, due in part to a lack of understanding of fundamental tendon cell biology. A major impediment to the study of tendon cells is the absence of robust, well-characterized in vitro models. Unlike other tissue systems, current tendon cell models do not account for how differences in isolation methodology may affect the activation state of tendon cells or the presence of various tendon cell subpopulations. The objective of this study was to characterize how common isolation methods affect the behavior, fate, and lineage composition of tendon cell cultures. Tendon cells isolated by explant exhibited reduced proliferative capacity, decreased expression of tendon marker genes, and increased expression of genes associated with fibroblast activation compared to digested cells. Consistently, explanted cells also displayed an increased propensity to differentiate to myofibroblasts compared to digested cells. Explanted cultures from multiple different tendons were substantially enriched for the presence of scleraxis-lineage (Scx-lin+) cells compared to digested cultures, while the overall percentage of S100a4-lineage (S100a4-lin+) cells was dependent on both isolation method and tendon of origin. Neither isolation methods preserved the ratios of Scx-lin+ or S100a4-lin+ to non-lineage cells seen in tendons in vivo. Combined, these data indicate that further refinement of in vitro cultures models is required in order to more accurately understand the effects of various stimuli on tendon cell behavior. Statement of clinical significance: The development of informed in vitro tendon cell models will facilitate enhanced screening of potential therapeutic candidates to improve tendon healing.

Executive Functions and Academic Outcomes of Low Birthweight Infants: A Prospective Longitudinal U.S. Cohort.

OBJECTIVE: Executive functions such as working memory and cognitive flexibility are key to lifelong learning. Our hypothesis was that children born low birthweight (LBW), defined as weight < 2,500 g, would have lower cognitive outcomes than those born normal weight, and children with poor executive functioning would be at risk for poor academic outcomes. STUDY DESIGN: We evaluated data from 12,656 children followed prospectively in the Early Childhood Longitudinal Study, Kindergarten Class 2010-2011, assessing outcomes from kindergarten, first grade, and second grade. Multivariable linear and logistic regressions were run evaluating the relationship between birthweight and cognitive outcomes, and the odds of infants with poor executive functioning having poor academic outcomes. RESULTS: Compared with children with normal birthweight, those born LBW had lower mean z-scores for academic and directly assessed executive functions from kindergarten through second grade. LBW children were at an increased risk of scoring in the bottom 20% of children at all time points: second-grade reading odds ratio (OR) = 1.60 (95% confidence interval [CI:] 1.23-2.09), math OR = 1.49 (95% CI: 1.21-1.84), science OR = 1.41 (95% CI: 1.11-1.81), cognitive flexibility OR = 1.61 (95% CI: 1.27-2.02), and working memory OR = 1.40 (95% CI: 1.10-1.77). CONCLUSION: LBW infants remain at risk of poor cognitive outcomes in second grade. Early difficulties with executive functioning can increase the risk of a child's academic performance years later.

MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML.

The tendency of 5-methylcytosine (5mC) to undergo spontaneous deamination has had a major role in shaping the human genome, and this methylation damage remains the primary source of somatic mutations that accumulate with age. How 5mC deamination contributes to cancer risk in different tissues remains unclear. Genomic profiling of 3 early-onset acute myeloid leukemias (AMLs) identified germ line loss of MBD4 as an initiator of 5mC-dependent hypermutation. MBD4-deficient AMLs display a 33-fold higher mutation burden than AML generally, with >95% being C>T in the context of a CG dinucleotide. This distinctive signature was also observed in sporadic cancers that acquired biallelic mutations in MBD4 and in Mbd4 knockout mice. Sequential sampling of germ line cases demonstrated repeated expansion of blood cell progenitors with pathogenic mutations in DNMT3A, a key driver gene for both clonal hematopoiesis and AML. Our findings reveal genetic and epigenetic factors that shape the mutagenic influence of 5mC. Within blood cells, this links methylation damage to the driver landscape of clonal hematopoiesis and reveals a conserved path to leukemia. Germ line MBD4 deficiency enhances cancer susceptibility and predisposes to AML.

Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer.

BACKGROUND: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed ex vivo macroscopically and microscopically and fluorescence was correlated with histopathology. RESULTS: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50 mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring < 5 mm) with a sensitivity of 88% (15/17 LNs). CONCLUSION: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.

Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging.

BACKGROUND: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor. METHODS: A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo. RESULTS: Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue. CONCLUSIONS: The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800.

INTRODUCTION: Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection. METHODS: Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. RESULTS: The mean TBR was significantly higher in tumor tissue of contrast-enhancing (CE) tumors on preoperative imaging (4.0 ± 0.5) compared to non-CE tumors (1.2 ± 0.3; p = 0.02). The TBR was higher at a 100 mg dose than at 50 mg (4.3 vs. 3.6). The smallest detectable tumor volume in a closed-field setting was 70 mg with 50 mg of dye and 10 mg with 100 mg. On sections of paraffin embedded tissues, fluorescence positively correlated with histological evidence of tumor. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (73.0% for 50 mg dose, 98.2% for 100 mg dose) and specific (66.3% for 50 mg dose, 69.8% for 100 mg dose) for viable tumor tissue in CE tumors while normal peri-tumoral tissue showed minimal fluorescence. CONCLUSION: This first-in-human study demonstrates the feasibility and safety of antibody based imaging for CE glioblastomas.

Determining the educational value of a technical and nontechnical skills medical student curriculum.

BACKGROUND: Residency application rates to general surgery remain low. The purpose of this study is to describe the educational value of a curriculum designed to increase preclinical medical student interest in surgical careers to better understand the process by which medical students decide to pursue a career in surgery. MATERIALS AND METHODS: We used qualitative methodology to describe the educational value of a technical and nontechnical skills curriculum offered to preclinical medical students at our institution. We conducted semistructured interviews of students and instructors who completed the curriculum in 2016. The interviews were recorded, transcribed, and inductively coded. The data were analyzed for emergent themes. RESULTS: A total of eight students and five instructors were interviewed. After analysis of 13 transcripts, four themes emerged: (1) The course provides a safe environment for learning, (2) acquisition and synthesis of basic technical skills increases preclinical student comfort in the operating room, (3) developing relationships with surgeons creates opportunities for extracurricular learning and scholarship, and (4) operative experiences can inspire students to explore a future career in surgery. CONCLUSIONS: These factors can help inform the design of future interventions to increase student interest, with the ultimate goal of increasing the number of students who apply to surgical residency programs.

Evaluation of a technical and nontechnical skills curriculum for students entering surgery.

BACKGROUND: Prior interventions to address declining interest in surgical careers have focused on creating early exposure and fostering mentorship at the preclinical medical student level. Navigating the surgical environment can be challenging, however, and preclinical students may be more likely to pursue a surgical career if they are given the tools to function optimally. MATERIALS AND METHODS: We designed a 10-wk technical and nontechnical skills curriculum to provide preclinical students with knowledge and skills necessary to successfully navigate the surgical learning environment, followed by placement in high-fidelity surgical simulations and scrubbing in on operative cases with attending surgeons. We administered pre-post surveys to assess student confidence levels in operative skills, self-perceptions of having a mentor, overall course efficacy, and interest in a career in surgery. RESULTS: The overall response rates presurvey and postsurvey were 100% (30 of 30) and 93.3% (28 of 30), respectively. Confidence levels across all operative skills increased significantly after completing the course. Faculty mentorship increased significantly from 30.0% before to 61.5% after the course. Overall effectiveness of the course was 4.00 of 5 (4 = "very effective"), and although insignificant, overall interest in a career in surgery increased at the completion of the course from 3.77 (standard deviation = 1.01) to 4.17 (standard deviation = 0.94). CONCLUSIONS: Our curriculum was effective in teaching the skills necessary to enjoy positive experiences in planned early exposure and mentorship activities. Further study is warranted to determine if this intervention leads to an increase in students who formally commit to a career in surgery.

Dietary omega-6 fatty acid replacement selectively impairs cardiac functional recovery after ischemia in female (but not male) rats.

A definitive understanding of the role of dietary lipids in determining cardioprotection (or cardiodetriment) has been elusive. Randomized trial findings have been variable and sex specificity of dietary interventions has not been determined. In this investigation the sex-selective cardiac functional effects of three diets enriched by omega-3 or omega-6 polyunsaturated fatty acids (PUFA) or enriched to an equivalent extent in saturated fatty acid components were examined in rats after an 8-wk treatment period. In females the myocardial membrane omega-6:omega-3 PUFA ratio was twofold higher than males in the omega-6 diet replacement group. In diets specified to be high in omega-3 PUFA or in saturated fat, this sex difference was not apparent. Isolated cardiomyocyte and heart Langendorff perfusion experiments were performed, and molecular measures of cell viability were assessed. Under basal conditions the contractile performance of omega-6 fed female cardiomyocytes and hearts was reduced compared with males. Omega-6 fed females exhibited impaired systolic resilience after ischemic insult. This response was associated with increased postischemia necrotic cell damage evaluated by coronary lactate dehydrogenase during reperfusion in omega-6 fed females. Cardiac and myocyte functional parameters were not different between omega-3 and saturated fat dietary groups and within these groups there were no discernible sex differences. Our data provide evidence at both the cardiac and cardiomyocyte levels that dietary saturated fatty acid intake replacement with an omega-6 (but not omega-3) enriched diet has selective adverse cardiac effect in females. This finding has potential relevance in relation to women, cardiac risk, and dietary management.

Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity.

The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE24 cleavage site, underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Likewise, mutations in the ZMPSTE24 gene that result in decreased enzyme function cause a spectrum of diseases that share certain features of premature aging. Twenty human ZMPSTE24 alleles have been identified that are associated with three disease categories of increasing severity: mandibuloacral dysplasia type B (MAD-B), severe progeria (atypical 'HGPS') and restrictive dermopathy (RD). To determine whether a correlation exists between decreasing ZMPSTE24 protease activity and increasing disease severity, we expressed mutant alleles of ZMPSTE24 in yeast and optimized in vivo yeast mating assays to directly compare the activity of alleles associated with each disease category. We also measured the activity of yeast crude membranes containing the ZMPSTE24 mutant proteins in vitro. We determined that, in general, the residual activity of ZMPSTE24 patient alleles correlates with disease severity. Complete loss-of-function alleles are associated with RD, whereas retention of partial, measureable activity results in MAD-B or severe progeria. Importantly, our assays can discriminate small differences in activity among the mutants, confirming that the methods presented here will be useful for characterizing any new ZMPSTE24 mutations that are discovered.

Academic performance in moderately and late preterm children in the United States: are they catching up?

OBJECTIVE: To determine whether preterm birth of 32-36 6/7 weeks gestation affected school performance from kindergarten through fifth grade. STUDY DESIGN: We assessed 14350 term infants and 1195 32-36 6/7 weeks gestation infants followed in the Early Childhood Longitudinal Study Kindergarten 2011 cohort for classroom performance in kindergarten-fifth grade. Multivariable regression was performed for comparisons, and data were weighted to be representative of the US population. RESULTS: Children born 35-36 6/7 weeks gestation had no significant difference in their academic scores or performance, while 32-34 6/7 weeks' children had lower academic scores and teacher performance scores when compared to term children. Children born between 32 and 36 6/7 weeks gestation had higher odds of individualized education plan needs and had learning disability diagnoses compared to term children. CONCLUSIONS: Children born between 32 and 34 6/7 weeks gestation have poor school performance compared to term children. Children born between 32 and 36 6/7 weeks gestation are at risk for learning disabilities and likely benefit from continued support and services to improve achievement throughout school.

A Case of an Obstructed Delivery by a Large, Lower Uterine Segment Fibroid Interlocked with a Fetal Mentum.

Uterine leiomyomata are associated with many pregnancy complications and will likely become increasingly common as the average age of childbearing increases. We describe a case of an obstructed delivery by a large fibroid. A 37-year-old G2P1001 with a 10-cm anterior, lower uterine segment fibroid presented for labor induction. Labor was complicated by arrest of descent due to suspected obstruction of the fetal body by the fibroid after descent of the fetal head, and delivery during cesarean section was complicated by apparent interlocking of the fetal mentum with the fibroid. Large, anterior lower uterine segment fibroids have the potential to obstruct delivery of the fetal head or of the fetal body, and these patients should be counseled regarding the potential for complications via both vaginal and cesarean deliveries.

Red Blood Cell Transfusion in Patients With Placenta Accreta Spectrum: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate red blood cell use during delivery in patients with placenta accreta spectrum. DATA SOURCES: We searched MEDLINE, EMBASE, CINAHL, Cochrane Central, ClinicalTrials.gov, and Scopus for clinical trials and observational studies published between 2000 and 2021 in countries with developed economies. METHODS OF STUDY SELECTION: Abstracts (n=4,275) and full-text studies (n=599) were identified and reviewed by two independent reviewers. Data on transfused red blood cells were included from studies reporting means and SDs, medians with interquartile ranges, or individual patient data. The primary outcome was the weighted mean number of units of red blood cells transfused per patient. Between-study heterogeneity was assessed with an I2 statistic. Secondary analyses included red blood cell usage by placenta accreta subtype. TABULATION, INTEGRATION, AND RESULTS: Of the 599 full-text studies identified, 20 met criteria for inclusion in the systematic review, comprising 1,091 cases of placenta accreta spectrum. The number of units of red blood cells transfused was inconsistently described across studies, with five studies (25.0%) reporting means, 11 (55.0%) reporting medians, and four (20.0%) reporting individual patient data. The weighted mean number of units transfused was 5.19 (95% CI 4.12-6.26) per patient. Heterogeneity was high across studies (I2=91%). In a sensitivity analysis of five studies reporting mean data, the mean number of units transfused was 6.61 (95% CI 4.73-8.48; n=220 patients). Further quantification of units transfused by placenta accreta subtype was limited due to methodologic inconsistencies between studies and small cohort sizes. CONCLUSION: Based on the upper limit of the CI in our main analysis and the high study heterogeneity, we recommend that a minimum of 6 units of red blood cells be available before delivery for patients with placenta accreta spectrum. These findings may inform future guidelines for predelivery blood ordering and transfusion support. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021240993.

Fasting Compared With Fed and Oral Intake Before the 1-Hour Oral Glucose Tolerance Test: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of fasting compared with eating before the 1-hour oral glucose tolerance test (OGTT) on gestational diabetes mellitus (GDM) screening results. METHODS: In a single-center, prospective randomized trial, participants were randomized to: 1) fasting for 6 or more hours or 2) oral intake ("fed") within 2 hours of the 50-g, 1-hour OGTT. The 1-hour OGTT was administered after 24 weeks of gestation. A positive screen result was defined as a serum glucose level of 140 mg/dL or higher. Protocol adherence was assessed by a survey administered immediately after the OGTT. We planned to enroll 100 participants in each group to detect an absolute difference of 20 percentage points or more on the 1-hour OGTT screen-positive rate using Fisher exact test, assuming an estimated screen-positive rate of 45% in the fasting and 25% in the fed group and 10% attrition, with a two-sided α=0.05, power=0.8. The primary outcome was the 1-hour OGTT screen-positive rate. Secondary outcomes included mean 1-hour OGTT glucose values, GDM diagnosis, maternal and neonatal outcomes, and patient perceptions regarding the 1-hour OGTT. RESULTS: From November 2020 through April 2021, 200 participants were randomized. One hundred ninety-five completed the 1-hour OGTT (97 fasting, 98 fed). Participant surveys confirmed 97.9% (n=95) adherence to the fasting and 91.8% (n=90) adherence to the fed groups. The screen-positive rate was significantly higher in the fasting than the fed group (32.0% vs 13.3%, respectively, P=.002), as was the mean glucose value (127.7 mg/dL vs 113.3 mg/dL, P=.002). The incidence of GDM in the fasting group was 12.4% (n=12) and in the fed group was 5.1% (n=5) (P=.08). There were no significant differences in maternal or neonatal outcomes. CONCLUSION: Fasting for 6 or more hours doubled the incidence of a positive 1-hour OGTT result when compared with eating within 2 hours of the test. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04547023.

Inhibitors of protein geranylgeranyltransferase-I lead to prelamin A accumulation in cells by inhibiting ZMPSTE24.

Protein farnesyltransferase (FTase) inhibitors, generally called "FTIs," block the farnesylation of prelamin A, inhibiting the biogenesis of mature lamin A and leading to an accumulation of prelamin A within cells. A recent report found that a GGTI, an inhibitor of protein geranylgeranyltransferase-I (GGTase-I), caused an exaggerated accumulation of prelamin A in the presence of low amounts of an FTI. This finding was interpreted as indicating that prelamin A can be alternately prenylated by GGTase-I and that inhibiting both protein prenyltransferases leads to more prelamin A accumulation than blocking FTase alone. Here, we tested an alternative hypothesis-GGTIs are not specific for GGTase-I, and they lead to prelamin A accumulation by inhibiting ZMPSTE24 (a zinc metalloprotease that converts farnesyl-prelamin A to mature lamin A). In our studies, commonly used GGTIs caused prelamin A accumulation in human fibroblasts, but the prelamin A in GGTI-treated cells exhibited a more rapid electrophoretic mobility than prelamin A from FTI-treated cells. The latter finding suggested that the prelamin A in GGTI-treated cells might be farnesylated (which would be consistent with the notion that GGTIs inhibit ZMPSTE24). Indeed, metabolic labeling studies revealed that the prelamin A in GGTI-treated fibroblasts is farnesylated. Moreover, biochemical assays of ZMPSTE24 activity showed that ZMPSTE24 is potently inhibited by a GGTI. Our studies show that GGTIs inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A. Thus, caution is required when interpreting the effects of GGTIs on prelamin A processing.

Central line-associated bloodstream infection prevention.

PURPOSE OF REVIEW: This review summarizes recent literature regarding the prevention of central line-associated bloodstream infection (CLABSI). RECENT FINDINGS: CLABSI rates in United States ICUs reported to the National Healthcare Safety Network (NHSN) have decreased dramatically in recent years. This has been achieved largely through a multifaceted approach and a focus on evidence-based best practices for central line insertion. More recent studies suggest an added benefit from implementation of evidence-based best practices for central line maintenance. Recent investigations also focus on CLABSI prevention among pediatric patients and in the non-ICU setting, in which a significant proportion of central line-days and CLABSI occur. A recent meta-analysis supports the practice of daily chlorhexidine gluconate (CHG) bathing in the ICU population for CLABSI prevention. Investigation continues regarding the most effective way to implement and sustain CLABSI prevention practices, including ways to best address and improve the culture of safety in healthcare. SUMMARY: Recent literature on CLABSI prevention shows that a multifaceted approach to improving central line insertion and maintenance practices results in decreased CLABSI rates in both the ICU and non-ICU settings. More data are needed to develop appropriate benchmarks and prevention strategies specific to the non-ICU setting, in which a significant proportion of central line-days and CLABSI occur.

Safety and efficacy of a home nasogastric monitoring program for premature infants.

BACKGROUND: A novel home monitoring program, in which premature infants are cared for at home with a nasogastric tube in place prior to achievement of full oral feeding, was evaluated. The program combines a digital, fully EMR-integrated, virtual daily rounding platform with direct provider video and telephone contact. METHODS: A case-control study was performed evaluating infants < 34 weeks' gestation who were followed in our program. A historical control group, was created by matching 2 : 1 based on gestational age±6 days, retroactively. RESULT: 15 patients discharged in the program were compared with 30 controls. The home cohort gained an average of 30 g/day compared with the in-hospital group at 27g/day (p = 0.325). The home group required a mean of 5.9±2.9 days to full oral feeding once discharged, not different from the control group at 5.4±3.7 days (p = 0.606). The percentage of oral feeds for the home cohort, however, increased at a rate of 12.2%before discharge compared to rising 57%at home (p < 0.001). The control group spent an additional 8.1±3.9 days in the hospital after reaching criteria. There were no reported adverse events or readmissions. CONCLUSION: Premature infants can safely advance oral feeds using a home monitoring program. While at home, infants gained weight similarly to their inpatient controls, yet gained full oral skills at a significantly faster rate compared to when they were in the hospital.

Genome Characterization of Gordonia Phage Amore2.

Novel Gordonia phage Amore2 was isolated from Pittsburgh, Pennsylvania and infects Gordonia terrae 3612. Amore2 was placed into Actinobacteria cluster CS1. Its genome is 73,842 bp with 105 predicted open reading frames and 56.6% GC content. The closest similarity of Amore2 is Gordonia phage Austin, with a 98% nucleotide identity.

Clinical factors associated with a positive postpartum depression screen in people with cardiac disease during pregnancy.

Background: While people with cardiac disease are known to be at increased lifetime risk of depression, little is known about postpartum depression rates in this population. Describing rates of positive postpartum depression screens and identifying risk factors that are unique to cardiac patients may help inform risk reduction strategies. Methods: This retrospective cohort study included pregnant patients with congenital and/or acquired cardiac disease who delivered at a single institution between 2014 and 2020. The primary outcome was a positive postpartum depression screen, defined as Edinburgh Postpartum Depression Score (EPDS) ≥10. Potential exposures were selected a priori and compared between patients with and without a positive postpartum depression screen using Wilcoxon rank-sum and Fisher's exact tests. Secondary outcomes were responses to a longitudinal follow-up survey sent to English-speaking patients evaluating cardiac status, mental health, and infant development. Results: Of 126 eligible cardiac patients, 23 (18.3%) had a positive postpartum depression screen. Patients with a positive postpartum depression screen were more likely to have had antepartum anticoagulation with heparin or enoxaparin (56.5% versus 26.2%, p=0.007), blood transfusion during delivery (8.7% versus 0%, p=0.032), and maternal-infant separation postpartum (52.2% versus 28.2%, p=0.047) compared to patients with a negative screen. Among 29 patients with a positive screen who responded to the follow up survey, 50% reported being formally diagnosed with anxiety or depression and 33.3% reported child development problems. Conclusions: Our results highlight the importance of screening for postpartum depression in patients with cardiac disease, especially those requiring antepartum anticoagulation or maternal-infant separation postpartum.