Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases.

Background: Immune responses to vaccination are a known trigger for a new onset of glomerular disease or disease flare in susceptible individuals. Mass immunization against SARS-CoV-2 in the COVID-19 pandemic provides a unique opportunity to study vaccination-associated autoimmune kidney diseases. In the recent literature, there are several patient reports demonstrating a temporal association of SARS-CoV-2 immunization and kidney diseases. Methods: Here, we present a series of 29 cases of biopsy-proven glomerular disease in patients recently vaccinated against SARS-CoV-2 and identified patients who developed a new onset of IgA nephropathy, minimal change disease, membranous nephropathy, ANCA-associated GN, collapsing glomerulopathy, or diffuse lupus nephritis diagnosed on kidney biopsies postimmunization, as well as recurrent ANCA-associated GN. This included 28 cases of de novo GN within native kidney biopsies and one disease flare in an allograft. Results: The patients with collapsing glomerulopathy were of Black descent and had two APOL1 genomic risk alleles. A brief literature review of patient reports and small series is also provided to include all reported cases to date (n=52). The incidence of induction of glomerular disease in response to SARS-CoV-2 immunization is unknown; however, there was no overall increase in incidence of glomerular disease when compared with the 2 years prior to the COVID-19 pandemic diagnosed on kidney biopsies in our practice. Conclusions: Glomerular disease to vaccination is rare, although it should be monitored as a potential adverse event.

Comprehensive genetic analysis of pregnancy loss by chromosomal microarrays: outcomes, benefits, and challenges.

PURPOSE: Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs). METHODS: Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH). RESULTS: A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative. CONCLUSION: Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.Genet Med 19 1, 83-89.

Placental pathology suggesting that preeclampsia is more than one disease.

OBJECTIVE: Our purpose was to evaluate the placental pathology in women with preeclampsia occurring at varying gestational ages. STUDY DESIGN: This was a secondary analysis of a prospective observational study of placentas from prespecified complicated pregnancies routinely submitted for standardized examination. For this study, a database of placental diagnoses from liveborn singleton gestations without major malformations was linked to a computerized obstetric database. The rates of standardized placental findings including vascular (atherosis, infarction) and nonvascular (hyperplasia) changes were evaluated according to gestational age at diagnosis of preeclampsia. RESULTS: Between Jan. 1, 2001, and Sept. 30, 2007, a total of 7122 women with pregnancies complicated by preeclampsia were delivered at our hospital. Of these, 1210 (17%) had placental examinations. Within this cohort, 209, 355, and 646 women were diagnosed with preeclampsia at gestations of 24(0/67) to 33(6/7), 34(0/7) to 36(6/7), and 37(0/7) weeks or longer, respectively. Placental findings revealed hypoplasia was significantly associated with preeclampsia early in the third trimester, and histological evidence of placental vascular lesions was significantly increased at gestations of 24(0/67) to 33(6/7) weeks (53%) compared with 34% and 26% at 34(0/7) to 36(6/7) and 37 weeks or longer, respectively (P < .001). CONCLUSION: The placentas of women with preeclampsia onset before 34 weeks' gestation were significantly different from those with preeclampsia at term. The former group demonstrated placental findings predominantly consistent with insufficiency because of vascular abnormalities. Such differing placental findings support the hypothesis that preeclampsia is a different disease, depending on the gestational age at diagnosis.

Bilateral mucinous cystadenomas and massive edema of the ovaries in a virilized adolescent girl.

BACKGROUND: Ovarian pathology, including nonfunctional tumors and massive edema of the ovary, has been associated with stromal luteinization and clinical endocrinopathies. CASE: An adolescent girl presented with primary amenorrhea, clitoromegaly, and large abdominopelvic mass. Laboratory evaluation revealed an elevated serum total testosterone level of 241 ng/dL. Magnetic resonance imaging confirmed three cystic adnexal structures, with the largest measuring 16 × 8 × 18 cm. Surgery with pelvic washings, bilateral ovarian cystectomies, unilateral paratubal cystectomy, and bilateral ovarian biopsies were performed. Pathology confirmed bilateral mucinous cystadenomas and massive edema of the ovaries. Postoperatively, the serum total testosterone level normalized. CONCLUSION: Nonfunctional ovarian tumors and massive edema of the ovaries should be considered in the differential diagnosis for a patient presenting with signs of hyperandrogenism.

An immunologic basis for placental insufficiency in fetal growth restriction.

OBJECTIVE: We sought to determine whether chronic villitis, an immunologic disease of the placenta, was related to fetal growth restriction. METHODS: Beginning in October 1999, a protocol was instituted that required placentas of high-risk births be submitted for standardized histological examination. Chronic villitis was diagnosed when a lymphohistiocytic infiltrate involving placental villi was present and was graded according to the extent and location of the infiltrate. Fetal growth restriction was defined as weight less than 3rd, 5th, and 10th percentiles. Placental hypoplasia was defined as weight less than 10th percentile. RESULTS: In the 10,204 placental examinations that were performed, low-grade and high-grade chronic villitis was associated with hypoplastic placentas and fetal growth restriction. Infants with placentas with low-grade and high-grade chronic villitis were more likely to require cesarean delivery for nonreassuring fetal heart rate compared with controls (27% and 25% versus 21%; p < 0.05). Fetal acidemia (umbilical artery pH < 7.0) was associated with high-grade chronic villitis compared with controls (4% versus 2%; p < 0.05). CONCLUSION: Chronic villitis was associated with anatomic and functional placental insufficiency manifested as placental hypoplasia, growth restriction, increased risk of cesarean for nonreassuring fetal heart rate, and fetal acidemia. These findings support an immunologic basis for fetal growth restriction.

A lean laboratory: operational simplicity and cost effectiveness of the Luminex xTAG™ respiratory viral panel.

During certain months of the year, viral respiratory infections lead to a dramatic increase in pediatric emergency room visits and hospital admissions. Rapid identification of the infectious organism results in timely treatment and reductions in hospital cost and length of stay. Before the introduction of molecular testing to the virology laboratory, diagnosis relied on the standard methods of immunofluorescence and culture. These tests can be labor-intensive and costly. Recent studies have demonstrated the higher sensitivity, faster turnaround, and broader diagnostic spectrum provided by multiplexed RT-PCR assays. Data comparing the laboratory cost and labor efficiency of the tests are lacking. To address this issue, we chose to implement the principles of operational workflow analysis using lean methodology to critically evaluate the potential advantages of a multiplexed RT-PCR assay both in terms of workflow and cost effectiveness. Our results indicated that the implementation of the Luminex xTAG Respiratory Viral Panel (RVP) resulted in a standardized workflow with decreased requirements in laboratory cost as well as improvement in efficiency. In summary, we demonstrate that, in our laboratory, the Luminex xTAG RVP is more operationally streamlined and cost-effective than standard viral direct fluorescent antibody and culture. Further studies are needed to highlight additional benefits of the test, including shortened hospital stay and improved patient outcome.