Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.

Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.

COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.

Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU: 2023.

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system. CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.

Executive Summary: Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU.

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based clinical practice guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among "unselected" patients due to the absence of data regarding the benefit and the potential harms of false positive alarms, the risk of alarm fatigue, and cost. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system (GPS). CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.

Defining the Nature and Clinicopathologic Significance of Mallory-Denk-like Inclusions in Ovarian Fibromas: A Potential Degenerative Phenomenon Associated With Torsion.

Mallory-Denk bodies (MBD), described in alcoholic hepatitis, are composed of intermediate filaments admixed with other proteins. These cytoplasmic inclusions are irregularly shaped and eosinophilic as seen under the light microscope. MBD-like inclusions have rarely been described outside the hepatobiliary tree. Though rare, intracytoplasmic inclusions have been reported in ovarian fibromas. This study evaluates a series of torsed ovarian fibromas with intracytoplasmic inclusions resembling MDBs. Forty-three ovarian fibromas were retrieved from the pathology archives. The H&E slides were evaluated for the presence of MBD-like inclusions and histologic evidence of torsion. The cases with histologic features of torsion were included in the study group while the nontorsed fibromas formed the control group. Among the 15 cases of fibromas with torsion, MBD-like intracytoplasmic inclusions were seen in 5 cases, predominantly in the interface between necrotic areas and viable stroma. None of the cases from the control group showed any inclusions. There was no significant difference in the size of the fibroma or patient demographics between cases with and without inclusions. The inclusions were positive for cytokeratin and ubiquitin while being negative for per acidic Schiff and periodic acid-Schiff with diastase reaction, in the 3 cases selected for immunohistochemistry and special stains. Electron microscopy of the index case revealed a predominance of type 3 Mallory hyaline. This is the first report describing MDB-like inclusions in ovarian fibromas. These MDB-like inclusions appear to be limited to a fraction of ovarian fibromas that underwent torsion, suggesting that these inclusions likely result from subacute hypoxic damage to the cells.

Diagnosis and Management of an Enlarging Placental Immature Teratoma: A Case Report.

The clinical imaging and pathology of a rare case of immature teratoma of the placenta is presented with a discussion of controversies related to classification and clinical suggestions for therapy and follow-up.

Retinoic acid from the meninges regulates cortical neuron generation.

Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

Triaging and Evaluation of Products of Conception in Abortions and Post-Partum Hemorrhage.

The proper evaluation of abortion specimens and placentas from stillbirth and post-partum cases is important for adequate clinical care of post-abortion and post-partum patients. The following topics will be reviewed: (1) the importance of evaluation of both fetal and placental tissue in first trimester abortions to confirm an intrauterine pregnancy versus an ectopic pregnancy; (2) the clinical history associated with an abortion specimen or retained products of conception (POC) influences how the pathologist should triage the specimen; (3) the criteria for diagnosis of a molar pregnancy, which is critical for clinicians to know which patients need follow-up; (4) the utility of genetic studies for both diagnosis and appropriate follow-up of the patient; and (5) the pathologic evaluation of specimens from patients with post-partum hemorrhage for placenta accreta spectrum and subinvolution of maternal vessels.

Caudal regression in fetus with de novo SMARCA2 pathogenic variant.

Nicolaides-Baraitser syndrome (NCBRS) is a rare autosomal dominant genetic condition that is characterized by severe intellectual disability, dysmorphic facial features, short stature, sparse hair, and early onset seizures. This diagnosis is established by suggestive clinical findings and the identification of a heterozygous SMARCA2 pathogenic variant by molecular genetic testing. There are not, however, consensus clinical diagnostic criteria for this condition as there are so few documented cases. Here, we present a case of prenatally diagnosed caudal regression with sacral agenesis and congenital vertical talus (rocker bottom feet) that was ultimately found to have a de novo SMARCA2 pathogenic variant. The patient had an amniocentesis with normal karyotype and microarray followed by failed direct rapid whole exome sequencing (WES) due to maternal cell contamination. She elected for termination of the pregnancy based on the clinical prognosis of the ultrasound findings; WES revealed a pathogenic variant after her termination. We believe this is the first case of these findings associated with NCBRS. If any future cases of either finding are found in association with a SMARCA2 genetic variant, caudal regression and rocker bottom feet should be included in the spectrum of physical traits associated with this pathogenic variant.

A systematic review of the facilitators and barriers to rapid response team activation.

BACKGROUND: Outcomes associated with rapid response teams (RRTs) are inconsistent. This may be due to underlying facilitators and barriers to RRT activation that are affected by team leaders and health systems. AIMS: The aim of this study was to synthesize the published research about facilitators and barriers to nurse-led RRT activation in the United States (U.S.). METHODS: A systematic review was conducted. Four databases were searched from January 2000 to June 2023 for peer-reviewed quantitative, qualitative, and mixed methods studies reporting facilitators and barriers to RRT activation. Studies conducted outside the U.S. or with physician-led teams were excluded. RESULTS: Twenty-five studies met criteria representing 240,140 participants that included clinicians and hospitalized adults. Three domains of facilitators and barriers to RRT activation were identified: (1) hospital infrastructure, (2) clinician culture, and (3) nurses' beliefs, attributes, and knowledge. Categories were identified within each domain. The categories of perceived benefits and positive beliefs about RRTs, knowing when to activate the RRT, and hospital-wide policies and practices most facilitated activation, whereas the categories of negative perceptions and concerns about RRTs and uncertainties surrounding RRT activation were the dominant barriers. LINKING EVIDENCE TO ACTION: Facilitators and barriers to RRT activation were interrelated. Some facilitators like hospital leader and physician support of RRTs became barriers when absent. Intradisciplinary communication and collaboration between nurses can positively and negatively impact RRT activation. The expertise of RRT nurses should be further studied.

Perinatal assessment of complex cesarean delivery: beyond placenta accreta spectrum.

Multiple cesarean deliveries are known to be associated with long-term postoperative consequences because of a permanent defect of the lower uterine segment wall and the development of thick pelvic adhesions. Patients with a history of multiple cesarean deliveries often present with large cesarean scar defects and are at heightened risk in subsequent pregnancies of cesarean scar ectopic pregnancy, uterine rupture, low-lying placenta or placenta previa, and placenta previa accreta. Moreover, large cesarean scar defects will lead to progressive dehiscence of the lower uterine segment with the inability to effectively reapproximate hysterotomy edge and repair at birth. Major remodeling of the lower uterine segment associated with true placenta accreta spectrum at birth, whereby the placenta becomes inseparable from the uterine wall, increases the rates of perinatal morbidity and mortality, especially when undiagnosed before delivery. Ultrasound imaging is currently not routinely used to evaluate the surgical risks of patients with a history of multiple cesarean deliveries, beyond the risk assessment of placenta accreta spectrum. Independent of accreta placentation, a placenta previa under a scarred, thinned partially disrupted lower uterine segment, covered by thick adhesions with the posterior wall of the bladder, poses a surgical risk and requires fine dissection and surgical expertise; however, data on the use of ultrasound to evaluate uterine remodeling and adhesions between the uterus and other pelvic organs are scarce. In particular, transvaginal sonography has been underused, including in patients with a high probability of placenta accreta spectrum at birth. Based on the best available knowledge, we discuss the role of ultrasound imaging in identifying the signs suggestive of major remodeling of the lower uterine segment and in mapping the changes in the uterine wall and pelvis, to enable the surgical team to prepare for all different types of complex cesarean deliveries. The need for postnatal confirmation of the prenatal ultrasound findings for all patients with a history of multiple cesarean deliveries, regardless of the diagnosis of placenta previa and placenta accreta spectrum, is discussed. We propose an ultrasound imaging protocol and a classification of the level of surgical difficulty at elective cesarean delivery to stimulate further research toward the validation of ultrasound signs by which these signs may be applied to improve surgical outcomes.

Knowledge Gaps in Placenta Accreta Spectrum.

Since its first description early in the 20th Century, placenta accreta and its variants have changed substantially in incidence, risk factor profile, clinical presentation, diagnosis and management. While systematic use of diagnostic tools and a multidisciplinary team care approach has begun to improve patient outcomes, the condition's pathophysiology, epidemiology, and best practices for diagnosis and management remain poorly understood. The use of large databases with broadly accepted terminology and diagnostic criteria should accelerate research in this area. Future work should focus on non-traditional phenotypes, such as those without placenta previa-preventive strategies, and long term medical and emotional support for patients facing this diagnosis. KEY POINTS: · Placenta accreta spectrum research may be improved with standardized terminology and use of large databases.. · Placenta accreta prediction should move beyond ultrasound with the addition of biomarkers, and needs to extend to those without traditional risk factors.. · Future research should identify practices that can prevent future accreta development..

Basal Plate Myofibers and the Risk of Placenta Accreta Spectrum in the Subsequent Pregnancy: A Large Single-Center Cohort.

OBJECTIVE: We aimed to evaluate whether there is a significant association between a placental pathology diagnosis basal plate myofibers (BPMF) in an index pregnancy with placenta accreta spectrum (PAS) in the subsequent pregnancy. STUDY DESIGN: We conducted a retrospective nested cohort study of all cases with a histopathological finding of BPMF between August 2012 and March 2020 at a single tertiary referral center. Data were collected for all subjects (cases and controls) with at least two consecutive pregnancies (the initial index pregnancy and at least one subsequent pregnancy) accompanied by a concomitant record of histopathological study of the placenta at our center. The primary outcome was pathologically confirmed PAS in the subsequent pregnancy. Data are presented as percentage or median, interquartile range accordingly. RESULTS: A total of n = 1,344 participants were included, of which n = 119 (index cases) carried a contemporaneous histopathological diagnosis of BPMF during the index pregnancy and n = 1,225 did not (index controls). Among the index cases, patients with BPMF were older (31.0 [20, 42] vs. 29.0 [15, 43], p < 0.001), more likely to have undergone in vitro fertilization (IVF) for conception (10.9 vs. 3.8%, p = 0.001) and were of a more advanced gestational age at delivery (39.0 [25, 41] vs. 38.0 [20, 42], p = 0.006). In the subsequent pregnancy, the rate of PAS was significantly higher among the BPMF index cases (6.7 vs. 1.1%, p < 0.001). After adjusting for maternal age and IVF, a histopathological diagnosis of BPMF in an index pregnancy was shown to be a significant risk factor for PAS in the subsequent gestation (hazard ratio: 5.67 [95% confidence interval: 2.28, 14.06], p < 0.001). CONCLUSION: Our findings support that a histopathological diagnosis of BPMF is an independent risk factor for PAS in the subsequent pregnancy. KEY POINTS: · BPMF may indicate morbid adherence of placenta.. · Patients with BPMF were older and more likely to have undergone IVF for conception.. · The BPMF in the current pregnancy is an independent risk factor for PAS in the subsequent pregnancy..

"The System Tends to Scoop You Up and Spit You Out and They're Done With You": The Intersection of Intellectual/Developmental Disability and Homelessness From the Perspectives of Service Providers.

People with intellectual and developmental disabilities (IDD) experience elevated risk for poor health and social outcomes in adulthood and are at risk for experiencing homelessness and housing instability. Although the exact prevalence of IDD among homeless populations is unknown, a small body of literature related to the intersection of IDD and homelessness suggests differential health needs and service use patterns, with a need for targeted health and social services. In this study, we explore the perceptions and experiences of 18 homeless or disability service providers about (a) their clients at the intersection of IDD and homelessness and (b) their role and the services provided at the intersection of IDD and homelessness. Participants struggled to provide appropriate, accessible services for this population, owing to lack of training and awareness of specific needs, fragmented systems, and inadequately funded healthcare and housing support. Our findings also reveal that clients at this intersection have high contact with public systems, which places them at risk for losing their right to self-determination. Recommendations center on systems transformation to facilitate the ability of providers to collaborate and to make data-driven decisions to deliver person-centered care.

Searching for placenta percreta: a prospective cohort and systematic review of case reports.

BACKGROUND: Placenta percreta is described as the most severe grade of placenta accreta spectrum and accounts for a quarter of all cases of placenta accreta spectrum reported in the literature. OBJECTIVE: We investigated the hypothesis that placenta percreta, which has been described clinically as placental tissue invading through the full thickness of the uterus, is a heterogeneous category with most cases owing to primary or secondary uterine abnormality rather than an abnormally invasive form of placentation. STUDY DESIGN: We have evaluated the agreement between the intraoperative findings using the International Federation of Gynecology and Obstetrics classification with the postoperative histopathology diagnosis in a prospective cohort of 101 consecutive singleton pregnancies presenting with a low-lying placenta or placenta previa, a history of at least 1 prior cesarean delivery and ultrasound signs suggestive of placenta accreta spectrum. Furthermore, a systematic literature review of case reports of placenta percreta, which included histopathologic findings and gross images, was performed. RESULTS: Samples for histologic examination were available in 80 of 101 cases of the cohort, which were managed by hysterectomy or partial myometrial resection. Microscopic examination showed evidence of placenta accreta spectrum in 65 cases (creta, 9; increta, 56). Of 101 cases included in the cohort, 44 (43.5%) and 54 (53.5%) were graded as percreta by observer A and observer B, respectively. There was a moderate agreement between observers. Of note, 11 of 36 cases that showed no evidence of abnormal placental attachment at delivery and/or microscopic examination were classified as percreta by both observers. The systematic literature review identified 41 case reports of placenta percreta with microscopic images and presenting symptomatology, suggesting that most cases were the consequence of a uterine rupture. The microscopic descriptions were heterogeneous, and all descriptions demonstrated histology of placenta creta rather than percreta. CONCLUSION: Our study supported the concept that placenta accreta is not an invasive disorder of placentation but the consequence of postoperative surgical remodeling or a preexisting uterine pathology and found no histologic evidence supporting the existence of a condition where the villous tissue penetrates the entire uterine wall, including the serosa and beyond.

The Society for Pediatric Pathology Task Force grading system for placenta accreta spectrum and its correlation with clinical outcomes.

BACKGROUND: The terminology and diagnostic criteria presently used by pathologists to report placenta accreta spectrum is inconsistent and does not reflect current knowledge of the pathogenesis of this disease. OBJECTIVE: In 2020, the perinatal subcommittee of the Society for Pediatric Pathology Placenta Accreta Task Force proposed a new pathologic grading system for placenta accreta spectrum. We sought to correlate the clinical outcomes with the classification into each group in the new placenta accreta spectrum grading system. STUDY DESIGN: The pathology reports of patients with histopathologic confirmation of placenta accreta spectrum were reviewed in 2 academic referral centers by placental pathologists. Pathologic grading was assigned based on the new grading system according to which placenta accreta spectrum is categorized into 5 groups depending on the depth of invasion, from grade p1 with no invasion into the uterine wall to grade p3E with invasion beyond the uterine wall to the adjacent organs. Patient characteristics and clinical outcomes were compared among these groups. A univariate analysis was performed, and a multivariate linear or binomial regression was employed when needed. RESULTS: A total of 683 patients with placenta accreta spectrum were identified. Of those, 407 were included for histology review. There were 92 patients (23%) categorized into the grade p1 group, 74 (18%) in the grade p2 group, 84 (20%) in the grade p3A group, 121 (30%) in the grade p3D group, and 36 (9%) in the grade p3E group. There was a significant association between the pathology grading and the number of red blood cells transfused (ß=1.14; 95% confidence interval, 0.48-1.79) and the postoperative complications including the rate of readmission (risk ratio, 1.93; 95% confidence interval, 1.26-2.94) and bladder injury (risk ratio, 1.81; 95% confidence interval, 1.23-2.68) after adjustment for antenatal diagnosis and other variables. The pathology grading was not associated with the estimated blood loss (P=.072). CONCLUSION: The new pathology grading system accurately reflects maternal outcomes and complications of placenta accreta spectrum. We encourage the utilization of this new pathologic grading system because it is designed to omit discrepancies in placenta accreta spectrum reporting and to standardize communication.

Ovarian Cystadenomas: Growth Rate and Reliability of Imaging Measurements.

OBJECTIVES: To evaluate the growth rate of benign ovarian cystadenomas and the degree of variability in ultrasound measurements. METHODS: Two independent retrospective cohorts of women found to have benign cystadenomas at surgery were identified. To assess growth rate, ultrasounds on women in a community-based health system were reviewed and the growth rate was determined based on the maximum reported size dimension using a mixed effect model. To assess measurement variability, two radiologists independently measured presurgical adnexal imaging findings for women in a tertiary care referral setting. Interobserver, intra-observer, and intermodality (cine clip versus still images) variability in measurements was determined using correlation coefficients (CC) and Bland-Altman analysis, with the proportion of measurements varying by more than 1 cm calculated. RESULTS: For growth rate assessment, 405 women with 1412 ultrasound examinations were identified. The median growth rate was 0.65 cm/year with mucinous cystadenomas growing faster at 0.83 cm/year compared to 0.51 cm/year for serous cystadenomas (median test P < .0001). To evaluate measurement variability, 75 women were identified with 176 ultrasound studies. The within-subject standard deviations for ultrasound measurements were 0.74 cm for cine clip images and 0.41 cm for static images, with 11% of measurements overall differing by more than 1 cm. CONCLUSIONS: Cystadenomas grow on average 0.65 cm/year, which is similar in magnitude to the inherent error observed in measurement on ultrasound, suggesting that repeat ultrasound at intervals of longer than a year will often be needed to accurately assess growth if a cyst represents a benign cystadenoma.

The Sonographic Appearance of Endometrial Intraepithelial Neoplasia.

OBJECTIVES: To describe the sonographic findings of endometrial intraepithelial neoplasia (EIN), a precursor of endometrial cancer. METHODS: Cases were found by word search of pathology database 1/2013 to 6/2019. One hundred and seventy-eight patients with ultrasound <1 year prior to biopsy were included. Medical records were searched for patient data. Two radiologists blindly classified images. Differences of opinion were decided by clinical report. Univariate and multivariate analyses were performed. RESULTS: Median time between ultrasound and first sampling procedure was 49 days. Median age was 55 (range 28-85) years. Endometrial thickness ranged from 2 to 90 mm. Mean endometrial thickness was 13 ± 6 mm in the noncancer group and 16 ± 11 mm in the cancer group (P = .02). The endometrium was almost always heterogeneous 175/178 (98%). Cysts were almost always multiple (89/109, 82%) and >1 mm (72/109, 66%). Masses were most often >5 mm (56/105, 55%) and ill-defined (41/105, 39%). Vascularity was present in 93/178 examinations (52%) and always associated with cysts and/or mass. There were 92 cancers, 25 with invasion (including 4 with tumor extension into adenomyosis). In 47 cases, the endometrial-myometrial interface was graded as ill-defined, 39 of whom had hysterectomy. There was macroscopic cancer in 11, microscopic cancer in 4, and invasive carcinoma in 12 patients (P for invasive cancer versus other outcomes = .02). Depth of invasion was 5- >95%, with 6 cancers >50%. Multivariate analysis showed thickness, polyps, and type of bleeding as the best set of independent variables for cancer (area under the receiver operating characteristic (ROC) curve [AUC] = .75). Replacing type of bleeding with age or menopausal status had AUC of .73 and .74, respectively. CONCLUSIONS: EIN has a variety of sonographic appearances with thickened endometrium with cysts and masses being common. Ill-definition of the endometrial-myometrial interface is a poor prognostic finding when seen in the absence of adenomyosis.

Complement activation and increased expression of Syk, mucin-1 and CaMK4 in kidneys of patients with COVID-19.

Acute and chronic kidney failure is common in hospitalized patients with COVID-19, yet the mechanism of injury and predisposing factors remain poorly understood. We investigated the role of complement activation by determining the levels of deposited complement components (C1q, C3, FH, C5b-9) and immunoglobulin along with the expression levels of the injury-associated molecules spleen tyrosine kinase (Syk), mucin-1 (MUC1) and calcium/calmodulin-dependent protein kinase IV (CaMK4) in the kidney tissues of people who succumbed to COVID-19. We report increased deposition of C1q, C3, C5b-9, total immunoglobulin, and high expression levels of Syk, MUC1 and CaMK4 in the kidneys of COVID-19 patients. Our study provides strong rationale for the expansion of trials involving the use of inhibitors of these molecules, in particular C1q, C3, Syk, MUC1 and CaMK4 to treat patients with COVID-19.