Anaphylaxis in Pregnancy.

Anaphylaxis in pregnancy is a rare event, but has important implications for the pregnant patient and fetus. The epidemiology, pathophysiology, diagnosis, and treatment all carry important considerations unique to the pregnant patient. Common culprits of anaphylaxis are primarily medications, particularly antibiotics and anesthetic agents. Diagnosis can be difficult given the relative lack of cutaneous symptoms, and normal physiologic changes in pregnancy such as low blood pressure and tachycardia. Apart from patient positioning, treatment is similar to that of the general population, with a focus on prompt epinephrine administration.

A Structured Peer Assessment Method with Regular Reinforcement Promotes Longitudinal Self-Perceived Development of Medical Students' Feedback Skills.

BACKGROUND: Given that training is integral to providing constructive peer feedback, we examined the impact of a regularly reinforced, structured peer assessment method on student-reported feedback abilities throughout a two-year preclinical Communication Skills course. METHODS: Three consecutive 32-student medical school classes were introduced to the Observation-Reaction-Feedback method for providing verbal assessment during Year 1 Communication Skills orientation. In biweekly small-group sessions, students received worksheets reiterating the method and practiced giving verbal feedback to peers. Periodic questionnaires evaluated student perceptions of feedback delivery and the Observation-Reaction-Feedback method. RESULTS: Biweekly reinforcement of the Observation-Reaction-Feedback method encouraged its uptake, which correlated with reports of more constructive, specific feedback. Compared to non-users, students who used the method noted greater improvement in comfort with assessing peers in Year 1 and continued growth of feedback abilities in Year 2. Comfort with providing modifying feedback and verbal feedback increased over the two-year course, while comfort with providing reinforcing feedback and written feedback remained similarly high. Concurrently, student preference for feedback anonymity decreased. CONCLUSIONS: Regular reinforcement of a peer assessment framework can increase student usage of the method, which promotes the expansion of self-reported peer feedback skills over time. These findings support investigation of analogous strategies in other medical education settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01242-w.

The Effect of Catheterization on Susceptibility of Uropathogens After Pelvic Reconstructive Surgery.

OBJECTIVE: The aim of this study was to determine whether bacterial uropathogens from positive urine cultures and uropathogen antibiotic susceptibility differ between catheterized (C) and noncatheterized (NC) patients after pelvic reconstructive surgery. METHODS: This is a retrospective cohort study of patients with a positive urine culture within 1 year of pelvic reconstructive surgery. Patients were categorized as having an indwelling catheter placed for urinary retention or voiding dysfunction within 48 hours of specimen collection versus no catheter. Microbiology reports provided uropathogens and antibiotic susceptibility for each culture. Student t test, χ, and logistic regression were used to compare rates of non-Escherichia coli uropathogens and susceptibility to first-line antibiotics between C and NC groups. RESULTS: A total of 427 positive urine cultures from 317 unique patients were identified. Positive urine cultures from C patients were less likely to contain E. coli (47.1% NC vs 29.2% C; P = 0.0009), with enterococcus being the most common non-E. coli uropathogen. The odds of non-E. coli uropathogens increased with age (adjusted odds ratio, 4.25; 95% confidence interval, 1.95-9.28; P = 0.0003 for the oldest patients). Cultures from C patients were more likely to have a uropathogen not susceptible to sulfamethoxazole/trimethoprim (20.5% NC vs 32.1% C; P = 0.03), nitrofurantoin (19.2% NC vs 34.6% C; P = 0.002), and cefazolin (18.1% NC vs 49.4% C; P < 0.0001). CONCLUSIONS: After pelvic reconstructive surgery, patients with a positive urine culture who have undergone catheterization within 48 hours of specimen collection are more likely to have non-E. coli uropathogens, with 1 in 3 cultures being not susceptible to common first-line antibiotics. This highlights the importance of performing susceptibility testing rather than treating empirically after pelvic reconstructive surgery.

Pregnancy-Associated Cardiac Hypertrophy in Corin-Deficient Mice: Observations in a Transgenic Model of Preeclampsia.

BACKGROUND: Preeclampsia increases the risk of heart disease. Defects in the protease corin, including the variant T555I/Q568P found in approximately 12% of blacks, have been associated with preeclampsia and cardiac hypertrophy. The objective of this study was to investigate the role of corin and the T555I/Q568P variant in preeclampsia-associated cardiac alterations using genetically modified mouse models. METHODS: Virgin wild-type (WT) and corin knockout mice with or without a cardiac WT corin or T555I/Q568P variant transgene were mated at 3 or 6 months of age. Age- and genotype-matched virgin mice were used as controls. Cardiac morphology and function were assessed at gestational day 18.5 or 28 days postpartum by histologic and echocardiographic analyses. RESULTS: Pregnant corin knockout mice at gestational day 18.5 developed cardiac hypertrophy. Such a pregnancy-associated phenotype was not found in WT or corin knockout mice with a cardiac WT corin transgene. Pregnant corin knockout mice with a cardiac T555I/Q568P variant transgene developed cardiac hypertrophy similar to that in pregnant corin knockout mice. The cardiac hypertrophy persisted postpartum in corin knockout mice and was worse if the mice were mated at 6 instead of 3 months of age. There was no hypertrophy-associated decrease in cardiac function in pregnant corin knockout mice. CONCLUSIONS: In mice, corin deficiency causes cardiac hypertrophy during pregnancy. Replacement of cardiac WT corin, but not the T555I/Q568P variant found in blacks, rescues this phenotype, indicating a local antihypertrophic function of corin in the heart. Corin deficiency may represent an underlying mechanism in preeclampsia-associated cardiomyopathies.

Deletion of the murine ortholog of the 8q24 gene desert has anti-cancer effects in transgenic mammary cancer models.

BACKGROUND: The gene desert on human chromosomal band 8q24 harbors multiple genetic variants associated with common cancers, including breast cancer. The locus, including the gene desert and its flanking genes, MYC, PVT1 and FAM84B, is also frequently amplified in human breast cancer. We generated a megadeletion (MD) mouse model lacking 430-Kb of sequence orthologous to the breast cancer-associated region in the gene desert. The goals were to examine the effect of the deletion on mammary cancer development and on transcript level regulation of the candidate genes within the locus. METHODS: The MD allele was engineered using the MICER system in embryonic stem cells and bred onto 3 well-characterized transgenic models for breast cancer, namely MMTV-PyVT, MMTV-neu and C3(1)-TAg. Mammary tumor growth, latency, multiplicity and metastasis were compared between homozygous MD and wild type mice carrying the transgenes. A reciprocal mammary gland transplantation assay was conducted to distinguish mammary cell-autonomous from non-mammary cell-autonomous anti-cancer effects. Gene expression analysis was done using quantitative real-time PCR. Chromatin interactions were evaluated by 3C. Gene-specific patient outcome data were analysed using the METABRIC and TCGA data sets through the cBioPortal website. RESULTS: Mice homozygous for the MD allele are viable, fertile, lactate sufficiently to nourish their pups, but maintain a 10% lower body weight mainly due to decreased adiposity. The deletion interferes with mammary tumorigenesis in mouse models for luminal and basal breast cancer. In the MMTV-PyVT model the mammary cancer-reducing effects of the allele are mammary cell-autonomous. We found organ-specific effects on transcript level regulation, with Myc and Fam84b being downregulated in mammary gland, prostate and mammary tumor samples. Through analysis using the METABRIC and TCGA datasets, we provide evidence that MYC and FAM84B are frequently co-amplified in breast cancer, but in contrast with MYC, FAM84B is frequently overexpressed in the luminal subtype, whereas MYC activity affect basal breast cancer outcomes. CONCLUSION: Deletion of a breast cancer-associated non-protein coding region affects mammary cancer development in 3 transgenic mouse models. We propose Myc as a candidate susceptibility gene, regulated by the gene desert locus, and a potential role for Fam84b in modifying breast cancer development.

The gene desert mammary carcinoma susceptibility locus Mcs1a regulates Nr2f1 modifying mammary epithelial cell differentiation and proliferation.

Genome-wide association studies have revealed that many low-penetrance breast cancer susceptibility loci are located in non-protein coding genomic regions; however, few have been characterized. In a comparative genetics approach to model such loci in a rat breast cancer model, we previously identified the mammary carcinoma susceptibility locus Mcs1a. We now localize Mcs1a to a critical interval (277 Kb) within a gene desert. Mcs1a reduces mammary carcinoma multiplicity by 50% and acts in a mammary cell-autonomous manner. We developed a megadeletion mouse model, which lacks 535 Kb of sequence containing the Mcs1a ortholog. Global gene expression analysis by RNA-seq revealed that in the mouse mammary gland, the orphan nuclear receptor gene Nr2f1/Coup-tf1 is regulated by Mcs1a. In resistant Mcs1a congenic rats, as compared with susceptible congenic control rats, we found Nr2f1 transcript levels to be elevated in mammary gland, epithelial cells, and carcinoma samples. Chromatin looping over ∼820 Kb of sequence from the Nr2f1 promoter to a strongly conserved element within the Mcs1a critical interval was identified. This element contains a 14 bp indel polymorphism that affects a human-rat-mouse conserved COUP-TF binding motif and is a functional Mcs1a candidate. In both the rat and mouse models, higher Nr2f1 transcript levels are associated with higher abundance of luminal mammary epithelial cells. In both the mouse mammary gland and a human breast cancer global gene expression data set, we found Nr2f1 transcript levels to be strongly anti-correlated to a gene cluster enriched in cell cycle-related genes. We queried 12 large publicly available human breast cancer gene expression studies and found that the median NR2F1 transcript level is consistently lower in 'triple-negative' (ER-PR-HER2-) breast cancers as compared with 'receptor-positive' breast cancers. Our data suggest that the non-protein coding locus Mcs1a regulates Nr2f1, which is a candidate modifier of differentiation, proliferation, and mammary cancer risk.