Abstract Pregnancy results in profound physiological changes driven by dynamic and precisely programmed molecular processes. Maternal peripheral blood is generally the specimen of choice for studying these processes, as it is easily accessible and essential for many aspects of maintaining a healthy pregnancy. Here, we present a high-resolution atlas of the dynamic temporal changes in the transcriptome of maternal peripheral blood in healthy human pregnancy. We generated comprehensive RNA sequencing data in 802 weekly samples from 31 healthy pregnant women from the first trimester until after delivery. Using a strict discovery and replication setup, our longitudinal analysis of gene expression identified 720 genes with robust pregnancy-specific expression patterns. Using weighted graph correlation network analysis, we identified nine pregnancy-associated transcriptional modules that reveal a strong, coordinated enrichment of innate/neutrophil and antiviral immune programs, alongside changes in adaptive immunity (T cell differentiation and signaling), erythropoiesis and hemoglobin metabolism. Cell-type deconvolution revealed that these transcriptomic shifts were accompanied by increased relative neutrophil proportions and reduced naive CD4 and CD8 T cells in pregnancy. We provide a comprehensive characterization of dynamic changes across pregnancy, highlighting maternal blood as a key systemic regulator in healthy gestation. Together, our findings establish a reference atlas of healthy pregnancy, which can be used to identify dysregulated processes and mechanisms in women with pregnancy complications. Graphical abstract 720 genes showed robust pregnancy specific expression patterns. Co-expression analysis clustered the genes into nine modules with distinct dynamics. Enrichment in pathways involved in innate and neutrophil-mediated immunity, antiviral responses, T cell differentiation and signaling, erythropoiesis and hemoglobin metabolism. Cell-type deconvolution showed increases in neutrophils and decreases in naïve CD4 and CD8 T cells. The atlas of detailed longitudinal transcriptional changes provides a baseline reference for healthy pregnancy. Results for all genes and protein-protein interaction networks are made available for interactive exploration.

Coronavirus disease 2019 (COVID-19) and active cancer are each independently associated with excess risk of thrombotic and cardiovascular events. However, data are limited regarding the risk of these events in outpatients with active cancer and concomitant COVID-19. Objectives:This study aimed to retrospectively examine the association between active cancer and thrombotic and cardiovascular outcomes among non-hospitalized patients with COVID-19. Methods:Data from the outpatient cohort with confirmed COVID-19 from the 10,420-patient multicenter U.S. CORONA-VTE Network registry were used. Active cancer was defined as having a malignancy diagnosis (excluding non-melanoma skin cancer) or receiving cancer-related treatment within the past year. Outcomes were independently adjudicated and included a composite of venous and arterial thromboembolism, and a composite of major adverse cardiovascular events, including thromboembolism, heart failure, myocarditis, new atrial fibrillation, and cardiovascular death within 90 days of COVID-19 diagnosis. Results:The registry included 6,576 outpatients, of whom 166 (2.5%) had active cancer (mean age 61 ± 16, 53% female). For outpatients with and without active cancer, the 90-day cumulative incidences of thromboembolism after developing COVID-19 were 4.2% and 1.2%, respectively (hazard ratio [HR]: 3.65; 95% confidence interval [CI]: 1.73-7.69, p  < 0.001). Corresponding 90-day cumulative incidences of cardiovascular events were 5.4% and 1.9% (HR: 2.97; 95% CI: 1.46-6.05, p  = 0.003). In adjusted analyses, non-hospitalized patients displayed an increased risk of thrombotic outcomes (HR: 2.48, 95% CI: 1.13-5.45, p  = 0.024) but not cardiovascular outcomes (HR: 1.76, 95% CI: 0.85-3.62, p  = 0.13). Conclusion:Outpatients with COVID-19 and active cancer demonstrated an increased hazard of thrombotic events compared with outpatients without cancer.

COVID-19 is associated with an increased risk of venous thromboembolism (VTE) in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We utilized data from hospitalized patients in the CORONA-VTE Network, a United States multicenter registry of adult patients with PCR-confirmed COVID-19 (N = 3,844). The primary outcome was time-to-first event for a composite of adjudicated pulmonary embolism or deep vein thrombosis during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. We conducted cause-specific Cox regression analysis adjusted for the selected variables for each imputed dataset and pooled the estimated HRs for reporting (p < 0.05 for significance). VTE occurred in 206 patients, with a cumulative incidence of 5.3

Background: Congenital heart disease (CHD) affects ~1% of infants. Hypoplastic left heart syndrome (HLHS), a severe form of CHD in which the left ventricle is underdeveloped, is associated by a 15% incidence of heart failure by 6 years of age. Only 6% of HLHS patients have a genetic cause identified on exome sequencing, limiting the ability of patients to receive a diagnosis and potentially benefit from targeted treatments. Hypothesis: Novel HLHS genes are differentially expressed in HLHS cardiac tissues, or in cells with differential abundance in HLHS hearts. Goals: To use single nucleus RNA sequencing of HLHS patient cardiac tissues to identify candidate HLHS genes. Methods: Single nucleus RNA sequencing (nucSeq) was performed on paired left and right ventricular tissues (LV, RV) from 9 participants with HLHS. Left ventricular cardiac tissues from children (4) and adults (12) without CHD were used for comparison. Filtering with CellBender and Solo were used to remove low-quality nuclei. Analysis was performed in R using the Seurat package. Results: HLHS LV tissues had a higher proportion of cardiomyocytes than pediatric or adult control tissues, (78.7% vs 64.1%, p=0.005; 78.7 % vs 47.0%, p=1.8E-08, respectively), and a lower proportion of mural cells (3.1% vs 9.3%, p=3.9E-05; 3.1 % vs 23.5%, p=7.3E-15, respectively). By contrast, there were similar proportions of endothelial cells in the HLHS, pediatric and adult tissues (7.1%, 8.8% and 7.9%, respectively; p=0.56). Within HLHS tissues, the LV had a higher proportion of cardiomyocytes than the RV (78.7% vs 51.2%, p=4.8E-04) while the proportion of endothelial cells were similar in the LV and RV (7.3% and 9.1%, respectively; p=0.33). LV tissues from HLHS participants 2-18 years of age had fewer capillary endothelial cells than pediatric controls (31.2% vs 57.8%, p=0.001), and gene markers of HLHS endothelial cells included PBX1 , which is required for Hox D-3 mediated angiogenesis, as well as ARHGAP26 and RORA, inhibitors of VEGF signaling. Conclusion: HLHS cardiac tissues have a higher proportion of cardiomyocytes in the LV despite a smaller chamber size. Differences in gene expression that accompany the differences in cell proportion could identify novel HLHS genes as well as potential therapeutic targets.

BACKGROUND:There is a lack of framework to incorporate equity into event analysis. This quality improvement initiative involved the development of equity tools that were introduced in a two-hour interactive, case-based training across 11 acute care facilities at the largest municipal health care system in the United States. A pre and post survey (which included analysis of a clinical vignette) was also conducted to assess for knowledge and comfort embedding equity in patient safety event analysis, and to measure discomfort or distress during the training. A separate assessment was used to evaluate the tools. EQUITY TOOLS:A visual aid, the Patient Equity Wheel, was created to facilitate more comprehensive and robust health equity discussions by compiling a comprehensive list of equity categories, including internal, external, and organizational dimensions of equity. The Wheel was designed for use during each phase of event analysis. An Embedding Equity in Root Cause Analysis Worksheet was developed to aid in assessing considerations of equitable care in the investigation process and includes questions to ask staff to further assess bias or equitable care factors. INITIATIVE OUTCOME AND KEY INSIGHTS:Participant knowledge and level of comfort increased after training. The most commonly unrecognized categories of bias were Training/Competencies, Structural Workflow, and Culture/Norms. Most participants responded that they had no discomfort or distress during the training. Post-training feedback noted that the tools were being used across the system in various stages of event analysis and have been reported to improve health equity conversations.

Abstract Introduction/Objective Malignant rhabdoid tumors (MRT) predominantly impact infants and young children, typically occurring around the age of 15 months. While they can emerge from soft tissues throughout the body, but commonly initiate in the kidneys. Neuroblastoma-like characteristics are seldom observed within the varied phenotypes of malignant rhabdoid tumors. Here, we present an exceptionally rare and distinctive subtype of malignant rhabdoid tumor exhibiting features akin to neuroblastoma localized within the unusal parapharyngeal space. Methods/Case Report A 2-month-old female presented to the ED with an enlarging right cervical neck mass. The mother reported a one-week history of upper respiratory tract symptoms and noticed an enlarging mass of her right neck. CT reported a “parapharyngeal abscess with airway compression”. The patient was started on Augmentin with no significant improvement. Repeat CT with contrast demonstrated an enlarging rim-enhancing 3 cm mass involving the right parapharyngeal space, trachea, and right carotid arteries. Laryngoscopy and incisional biopsy of right neck lymph nodes demonstrated a high-grade malignancy with prominent nucleoli, high N/C ratio and scant cytoplasm. The tumor tested positive for CD 99, synaptophysin, and neurofilament, leading to the initial diagnosis of neuroblastoma. However, molecular analysis uncovered the loss of INI-1 on 22q11.2, prompting a reevaluation and a final diagnosis of MRT with neuroblastoma-like characteristics was made. Results (if a Case Study enter NA) NA Conclusion A range of tumors displaying distinct “rhabdoid” cytological features are collectively termed as malignant rhabdoid tumors (MRTs). Conventional immunohistochemistry (IHC) staining for CD99, synaptophysin, neurofilament, and myogenin might suggest neuroblastoma, Ewing sarcoma, or rhabdomyosarcoma. However, the absence of INI-1 expression provides a definitive diagnosis. INI-1 loss, a purported tumor suppressor gene located on chromosome 22q11.2, solidifies the tumor’s classification as malignant rhabdoid tumor (MRT). Additionally, a positive neurofilament stain in MRT is crucial for diagnostic and therapeutic assessments. This differentiation is vital, given the dismal prognosis of MRT with a 5-year survival rate of less than 10%.

Background: Endocardial fibroelastosis (EFE) is marked by a thickened fibro-elastic layer derived by endothelial-to-mesenchymal transition (EndMT), leading to restrictive myocardial function and poor cardiac growth, complicating biventricular repair in hypoplastic left heart complex (HLHC) patients. Neuregulin (NRG) signaling, crucial in EndMT and myocardial development, is implicated in various cardiomyopathies and heart failure, and its dysregulation may drive EFE pathogenesis. Hypothesis: NRG signaling dysregulation influences the cellular and molecular mechanisms of EFE. Methods: Single nucleus RNA sequencing (snRNA-seq) was conducted on human left ventricular (LV) tissue resected from 7 EFE patients (0.4-15 years) and 4 non-congenital heart disease (CHD) postmortem human controls (0.02-16 years). Differential gene expression was analyzed using the Wilcoxon Rank Sum test. We used CellChat, a computational tool for analyzing intercellular communication networks, to identify signaling changes via quantitative contrasts and joint manifold learning. Results: We identified 11 cell types in 64,963 nuclei. In EFE samples compared to non-CHD samples, NRG1-expressing fibroblasts increased from 3.4% to 21.2% (P<0.0001), and NRG2-expressing cardiomyocytes from 11.9% to 45.9% (P<0.001). CellChat analysis revealed a denser NRG signaling network in EFE, with enhanced interactions among cardiomyocytes, endocardial cells, fibroblasts, mast cells, and smooth muscle cells (Fig. 1A-B). Cardiomyocytes emerged as significant senders of NRG signaling in EFE, while endocardial cells, though still key senders, showed reduced influence. Fibroblasts became strong mediators, receivers, and influencers, smooth muscle cells emerged as prominent receivers, and mast cells gained roles as mediators and influencers (Fig. 1 C-D). These changes indicate a complex NRG signaling network in EFE, highlighting altered cellular interactions driving disease progression. Conclusion: Dysregulated NRG signaling in EFE contributes to pathological cellular crosstalk, fibrosis, and myocardial dysfunction, potentially hindering successful biventricular repair in HLHC patients. Targeting NRG pathways could represent a novel therapeutic approach. These findings offer promising implications for affected patients, potentially improving outcomes. Future research should explore additional molecular pathways involved in EFE and assess the therapeutic efficacy of targeting NRG signaling.

Introduction: Babesia is endemic in the northeast and upper midwestern United States. Two species that cause human infections are Babesia microti and Babesia divergens. The parasite is transmitted by the bite of the tick Ixodes scapularis. Another mode of transmission is blood transfusion producing either an asymptomatic to mild flu-like illness or hemolytic anemia in immunocompromised and asplenic individuals. Hemolysis is usually non-immune and attributed to lysis of infected erythrocytes. Rarely the infection may cause immune dysregulation and lead to the formation of autoantibodies that cause immune mediated hemolytic anemia. Case Report: A previously healthy young adult male with a recent history of multiple blood transfusions, presented with refractory autoimmune hemolytic anemia within two months of transfusion. The anemia was unresponsive to various immunosuppressive medications and blood transfusions. On follow-up, his peripheral smears showed heavy parasitemia consistent with Babesia species. The organism was speciated to Babesia microti by polymerase chain reaction at the Center for Disease Control. The patient was treated with intravenous quinidine and oral clindamycin. Immune hemolytic anemia resolved following the treatment of Babesiosis. Conclusion: In conclusion, Babesiosis should be in the differential diagnosis of autoimmune hemolytic anemia in a patient with a history of blood transfusion and poor response to steroids or immunosuppressive drugs.

BACKGROUND:There is growing evidence that pathogenic mutations do not fully explain hypertrophic (HCM) or dilated (DCM) cardiomyopathy phenotypes. We hypothesized that if a patient's genetic background was influencing cardiomyopathy this should be detectable as signatures in gene expression. We built a cardiomyopathy biobank resource for interrogating personalized genotype phenotype relationships in human cell lines. METHODS:We recruited 308 diseased and control patients for our cardiomyopathy stem cell biobank. We successfully reprogrammed PBMCs (peripheral blood mononuclear cells) into induced pluripotent stem cells (iPSCs) for 300 donors. These iPSCs underwent whole genome sequencing and were differentiated into cardiomyocytes for RNA-seq. In addition to annotating pathogenic variants, mutation burden in a panel of cardiomyopathy genes was assessed for correlation with echocardiogram measurements. Line-specific co-expression networks were inferred to evaluate transcriptomic subtypes. Drug treatment targeted the sarcomere, either by activation with omecamtiv mecarbil or inhibition with mavacamten, to alter contractility. RESULTS:We generated an iPSC biobank from 300 donors, which included 101 individuals with HCM and 88 with DCM. Whole genome sequencing of 299 iPSC lines identified 78 unique pathogenic or likely pathogenic mutations in the diseased lines. Notably, only DCM lines lacking a known pathogenic or likely pathogenic mutation replicated a finding in the literature for greater nonsynonymous SNV mutation burden in 102 cardiomyopathy genes to correlate with lower left ventricular ejection fraction in DCM. We analyzed RNA-sequencing data from iPSC-derived cardiomyocytes for 102 donors. Inferred personalized co-expression networks revealed two transcriptional subtypes of HCM. The first subtype exhibited concerted activation of the co-expression network, with the degree of activation reflective of the disease severity of the donor. In contrast, the second HCM subtype and the entire DCM cohort exhibited partial activation of the respective disease network, with the strength of specific gene by gene relationships dependent on the iPSC-derived cardiomyocyte line. ADCY5 was the largest hubnode in both the HCM and DCM networks and partially corrected in response to drug treatment. CONCLUSIONS:We have a established a stem cell biobank for studying cardiomyopathy. Our analysis supports the hypothesis the genetic background influences pathologic gene expression programs and support a role for ADCY5 in cardiomyopathy.

IntroductionPregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.Materials & methodsWe analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and for men ≤45 years, as points of reference.ResultsAmong 6585 outpatients, 169 were pregnant at diagnosis. By 90-day follow-up, two pregnant women during the third trimester had lower extremity venous thrombosis, one deep and one superficial vein thrombosis. The cumulative incidence of thrombotic events was 1.20 % (95 % confidence interval [CI]: 0.0 to 2.84 %). Respective rates were 0.47 % (95 % CI: 0.14 % to 0.79 %) among non-pregnant women, and 0.49 % (95 % CI: 0.06 % to 0.91 %) among men ≤45 years. No non-thrombotic cardiovascular events occurred in pregnant women. The rates of cardiovascular events were 0.53 % (95 % CI: 0.18 to 0.87) among non-pregnant women, and 0.68 % (95 % CI: 0.18 to 1.18) in men aged ≤45 years.ConclusionsThrombotic and cardiovascular events are rare among outpatients with COVID-19. Although a higher event rate among outpatient pregnant women cannot be excluded, the absolute event rates are low and do not warrant population-wide cardiovascular interventions to optimize outcomes.

Malignant melanoma is a common and aggressive skin cancer with a high incidence of metastases. Diagnosis is usually straightforward, based on a combination of histomorphology and immunohistochemistry. However, metastatic melanoma is notorious for its phenotypic diversity and loss of differentiation markers. Through recent developments in diagnostic immunohistochemistry and molecular pathology, several new markers are identified to be of use in confirming melanoma diagnosis, especially in undifferentiated and dedifferentiated cases. Here we report a challenging case of a 59-year-old male with splenic metastatic melanoma which revealed a loss of four diagnostic melanocytic markers including S100, SOX-10, HMB45, and MART-1, but a gain of SOX-11.

Primary mandibular telangiectatic osteosarcomas are very rare lesions, with only nine cases reported. Histologically, these lesions show multiple cystic blood-filled cavities traversed by neoplastic bone in septa lined by high-grade malignant cells. Here, we report an 81-year-old woman who presented with a mandibular mass, which was surgically resected and analyzed by histologic examination and whole exome DNA sequencing. A diagnosis of telangiectatic osteosarcoma was given. Comparative sequencing data analysis of paired benign and tumor DNA revealed 1577 variants unique to the tumor DNA, which clustered into several gene families, including those regulating DNA repair and apoptosis. Comparison of benign and tumor DNA revealed many shared gene polymorphisms associated with an increased cancer risk. These included polymorphisms in the ATM, p53, BRCA1, and BRCA2 and many other genes. Interestingly, the patient's family history showed an unusually high cancer incidence, likely related to these cancer risk-associated polymorphisms. To our knowledge, this is the first-time sequencing applied to a mandibular telangiectatic osteosarcoma. Our findings may shed light on the molecular origins of these rare tumors and how they may relate to other tumors in related kindreds.

Introduction: Patients with COVID-19 are at an increased risk of cardiovascular complications. Studies indicating an association between ABO blood groups and risk of cardiovascular outcomes were limited by small sample size or use of administrative claims data with uncertain validity. Aim: To study the association of non-O blood group and cardiovascular outcomes among patients with COVID-19 in a large cohort with adjudicated cardiovascular events. Methods: We examined patients from the CORONA-VTE Network registry with confirmed COVID-19 and ABO blood group data. The main outcome was major cardiovascular events including venous or arterial thrombosis, heart failure, myocarditis, new atrial fibrillation/flutter, and cardiovascular death. Outcomes were assessed at 90-day follow-up and adjudicated by independent physicians. Adjusted analyses were conducted accounting for age, sex, cancer, history of cardiovascular disease, history of hemodialysis, history of prior venous thromboembolism, and clustering of patients within sites. Results: Among 3,224 patients of whom 1,658 were inpatients (mean age: 66 ± 17.8) and 1,566 were outpatients (mean age: 52 ± 17.8), 767 (23.8%) inpatients and 728 (22.6%) outpatients had blood group O. Among inpatients, 90-day cumulative incidence of cardiovascular events was 16.9% (95% CI: 14.1-19.5%) for blood group O and 20.8% (95% CI: 18.1- 23.4%) for non-O blood group. Compared with patients with blood group O, those with non-O blood group had a higher risk of cardiovascular events in unadjusted (HR: 1.28, 95% CI: 1.02-1.60%, p=0.03), and adjusted analyses (HR: 1.26, 95% CI: 1.02-1.57%, p=0.04). In outpatients, 90-day event rates were 2.9% (95% CI: 1.7- 4.1%) for blood group O and 4.2% (95% CI: 2.8- 5.6%) for non-O blood group. The risk of cardiovascular events in outpatients with non-O blood group did not reach statistical significance, in unadjusted (HR: 1.46, 95% CI: 0.9-2.5, p=0.172) or adjusted analyses (HR: 1.36, 95% CI: 0.9-2.1, p=0.162). Conclusion: Inpatients with COVID-19 with non-O blood group have a higher risk of cardiovascular events in unadjusted and adjusted analyses. Future studies should explore if patients with non-O blood group may benefit from preventive strategies to mitigate this risk.

Background: Active cancer and COVID-19 are each independently associated with excess risk of thrombotic and cardiovascular outcomes. Data are limited regarding the risk of these outcomes in patients with both active cancer and COVID-19. Aim: To examine the association between active cancer and thrombotic and cardiovascular outcomes among patients with COVID-19. Methods: Data from patients with confirmed COVID-19 from the multicenter CORONA-VTE Network registry were used. Active cancer was defined as having a malignancy diagnosis within the past year or receiving related treatment. Outcomes were adjudicated and included (1) a composite of venous and arterial thromboembolism and (2) a composite of major adverse cardiovascular events, including thromboembolism, heart failure, myocarditis, new atrial fibrillation, and cardiovascular death within 90 days of COVID-19 diagnosis. Results: The registry included 3,844 inpatients and 6,576 outpatients, of whom 247 (6.4%) and 199 (3.0%) had active cancer, respectively. For inpatients with and without cancer, the cumulative incidences of thromboembolism were 8.6% and 8.3%, respectively (hazard ratio [HR:1.05; 95% Confidence Interval [CI]: 0.68-1.64, P = 0.82) (Figure). The corresponding cumulative incidences of cardiovascular events were 16.1% and 15.3% (HR: 1.04; 95% CI: 0.75-1.45, P = 0.79). For outpatients with and without cancer, the cumulative incidences of thromboembolism were 3.6% and 1.2%, respectively (HR: 3.07; 95% CI: 1.41-6.67, P = 0.005). Corresponding cumulative incidences of cardiovascular events were 4.6% and 1.9% (HR: 2.47; 95% CI: 1.25-4.86, P = 0.009). Conclusions: There was no significant difference in the incidence of thrombotic or cardiovascular events among inpatients with and without active cancer, yet outpatients with COVID-19 and active cancer demonstrated a significantly increased hazard of thrombotic and cardiovascular events compared with non-cancer outpatients.

Background: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and throm-botic events in the early post-infection period and during convalescence. Despite the progress in our under-standing of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. Methods: Adult patients, aged & GE;18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Out-comes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. Conclusions: The CORONA-VTE-Network study will share contemporary information related to rates of cardio-vascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) is currently accepted to be a true neoplasm with a wide spectrum of biological behavior, varying from benign lesions to the rare tumors which are multifocal and prone to recurrence. IMT is characterized by a proliferation of myofibroblastic spindle cells with an inflammatory infiltrate. It was first described in the lung and later on reported in various sites such as stomach, intestine, spleen, bone. Here we report a rare IMT case in that the tumor penetrates through skull and extends to the dura. Methods/Case Report A 29-year-old female presented with a slowly progressive upper head scalp mass of one-year duration. Magnetic resonance imaging showed a soft tissue mass that extended through the skull and into the dura. Patient denies headache, syncopal episodes, neck pain, back pain, radicular symptoms, weakness, ataxia, nausea, vomiting, bladder or bowel incontinence, saddle anesthesia, or changes from baseline hearing, vision, or speech. Grossly, serial sectioning of the scalp skin specimen revealed a well-circumscribed mass lesion with white, firm, and homogeneous cut surface, with no hemorrhage or necrosis identified. The lesion measured 7.0 x 6.5 x 1.7 cm in greatest dimension. The lesion involved the deep margin and extended to the skull and dura. On histopathological examination, the lesion was composed of variable admixture of spindle cells with eosinophilic cytoplasm and inflammatory cells comprising of plasma cells and lymphocytes. The spindle cells were positive for smooth muscle actin, CD10 (partial), and negative for AE1/AE3, ALK–1, CD34, CD68, CD117, Desmin, Myogenin, p53, S-100, and SOX-10. The Ki-67 showed a spindle cell proliferation index at about 2%. The patient successfully went through surgery and was followed up without complications. Results (if a Case Study enter NA) NA Conclusion Our case showed a rare IMT case harboring histologically benign features like low cellularity, minimal nuclear atypia, and low proliferative index, but demonstrating locally very aggressive biological behaviors. Complete surgical resection and close follow up are suggested to avoid recurrence. Further studies are needed in this field to design in-depth investigation for accurate diagnosis and better clinical outcomes.