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OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.
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Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Pene , Humanos , Masculino , Neoplasias del Pene/virología , Neoplasias del Pene/patología , Neoplasias del Pene/mortalidad , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Anciano , Inmunohistoquímica , Adulto , Hibridación in Situ , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Estudios Retrospectivos , Anciano de 80 o más Años , Factores de Riesgo , Pronóstico , Progresión de la Enfermedad , Valor Predictivo de las Pruebas , Virus del Papiloma HumanoRESUMEN
The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112-7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.
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Carcinoma de Células Escamosas , Estadificación de Neoplasias , Neoplasias del Pene , Humanos , Neoplasias del Pene/patología , Neoplasias del Pene/virología , Masculino , Estadificación de Neoplasias/métodos , Estadificación de Neoplasias/normas , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Persona de Mediana Edad , Anciano , Adulto , Pronóstico , América del Norte , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. METHODS: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. RESULTS: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. CONCLUSIONS: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.
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COVID-19 , Placenta , Embarazo , Femenino , Humanos , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2/genética , Trofoblastos/metabolismo , Transcriptoma , ARN Mensajero/metabolismoAsunto(s)
Dirofilaria , Dirofilariasis , Humanos , Animales , Florida , Zoonosis , Dirofilariasis/diagnósticoRESUMEN
Villitis of unknown etiology (VUE) is a prevalent inflammatory pathology of the placenta characterized by infiltration of maternal T cells and accumulation of fetal macrophages into chorionic villi. VUE is associated with a variety of adverse clinical outcomes, including fetal growth restriction and fetal demise. Evaluation of the phenotypic and functional differences between two immune cell types associated with this pathology, namely T cells and macrophages, was completed to gain a deeper understanding of the immuno-pathogenesis of VUE. GeoMx Digital Spatial Profiling was performed on placental tissue from 4 high grade VUE cases and 4 controls with no underlying pathology. Placental tissues were fluorescently labeled with CD3 and CD68 antibodies and oligo-conjugated antibodies against 48 protein targets. Overall, T cells in VUE exhibited upregulated markers of activation, memory, and antigen experience compared to controls and were altered based on placental location (villi vs. decidua). Additionally, villous macrophages in VUE upregulated costimulatory and major histocompatibility complex class I and II molecules compared to controls and macrophage subtypes in the decidua. Data herein provides new mechanistic insights into T cell and macrophage biology in VUE which contribute to this abnormal immune response to pregnancy.
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Corioamnionitis , Placenta , Embarazo , Femenino , Humanos , Proteómica , Linfocitos T , MacrófagosRESUMEN
This paper discusses some overlooked challenges faced when working with machine learning models for histopathology and presents a novel opportunity to support "Learning Health Systems" with them. Initially, the authors elaborate on these challenges after separating them according to their mitigation strategies: those that need innovative approaches, time, or future technological capabilities and those that require a conceptual reappraisal from a critical perspective. Then, a novel opportunity to support "Learning Health Systems" by integrating hidden information extracted by ML models from digitalized histopathology slides with other healthcare big data is presented.
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Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.
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Enfermedades Autoinmunes , Productos Biológicos , Corioamnionitis , Enfermedades Placentarias , Recién Nacido , Humanos , Embarazo , Femenino , Placenta/patología , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Enfermedades Placentarias/diagnóstico , Vellosidades Coriónicas/patología , Estudios Retrospectivos , Resultado del Embarazo , Retardo del Crecimiento Fetal/inducido químicamente , Retardo del Crecimiento Fetal/patología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Productos Biológicos/efectos adversosRESUMEN
Numerous machine learning (ML) models have been developed for breast cancer using various types of data. Successful external validation (EV) of ML models is important evidence of their generalizability. The aim of this systematic review was to assess the performance of externally validated ML models based on histopathology images for diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer. A systematic search of MEDLINE, EMBASE, CINAHL, IEEE, MICCAI, and SPIE conferences was performed for studies published between January 2010 and February 2022. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed, and the results were narratively described. Of the 2011 non-duplicated citations, 8 journal articles and 2 conference proceedings met inclusion criteria. Three studies externally validated ML models for diagnosis, 4 for classification, 2 for prognosis, and 1 for both classification and prognosis. Most studies used Convolutional Neural Networks and one used logistic regression algorithms. For diagnostic/classification models, the most common performance metrics reported in the EV were accuracy and area under the curve, which were greater than 87% and 90%, respectively, using pathologists' annotations/diagnoses as ground truth. The hazard ratios in the EV of prognostic ML models were between 1.7 (95% CI, 1.2-2.6) and 1.8 (95% CI, 1.3-2.7) to predict distant disease-free survival; 1.91 (95% CI, 1.11-3.29) for recurrence, and between 0.09 (95% CI, 0.01-0.70) and 0.65 (95% CI, 0.43-0.98) for overall survival, using clinical data as ground truth. Despite EV being an important step before the clinical application of a ML model, it hasn't been performed routinely. The large variability in the training/validation datasets, methods, performance metrics, and reported information limited the comparison of the models and the analysis of their results. Increasing the availability of validation datasets and implementing standardized methods and reporting protocols may facilitate future analyses.
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OBJECTIVES: Recent work has demonstrated that automated fluorescence flow cytometry (FLC) is a potential alternative for the detection and quantification of Plasmodium parasites. The objective of this study was to apply this novel FLC method to detect and quantify Babesia parasites in venous blood and compare results to light microscopy and polymerase chain reaction methods. METHODS: An automated hematology/malaria analyzer (XN-31; Sysmex) was used to detect and quantify B microti-infected red blood cells from residual venous blood samples (n = 250: Babesia positive, n = 170; Babesia negative, n = 80). As no instrument software currently exists for Babesia, qualitative and quantitative machine learning (ML) algorithms were developed to facilitate analysis. RESULTS: Performance of the ML models was verified against the XN-31 software using P falciparum-infected samples. When applied to Babesia-infected samples, the qualitative ML model demonstrated an area under the curve (AUC) of 0.956 (sensitivity, 95.9%; specificity, 83.3%) relative to polymerase chain reaction. For valid scattergrams, the qualitive model achieved an AUC of 1.0 (sensitivity and specificity, 100%), while the quantitative model demonstrated an AUC of 0.986 (sensitivity, 94.4%; specificity, 100%). CONCLUSIONS: This investigation demonstrates that Babesia parasites can be detected and quantified directly from venous blood using FLC. Although promising, opportunities remain to improve the general applicability of the method.
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Babesia , Babesiosis , Eritrocitos , Citometría de Flujo , Citometría de Flujo/métodos , Humanos , Babesiosis/diagnóstico , Babesiosis/sangre , Eritrocitos/parasitología , Babesia/aislamiento & purificación , Babesia/genética , Aprendizaje Automático , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To evaluate maternal risk factors associated with chronic villitis of unknown etiology (VUE) and to describe cooccurring placental pathologies. STUDY DESIGN: A retrospective case-control study was conducted using placental pathology records from deliveries ≥ 20 weeks between 2010 and 2018. Cases were placentas with documented chronic villitis without infectious cause, hereafter called VUE. Controls were placentas without this diagnosis, matched to the cases 2:1. Maternal and neonatal demographic and clinical data were collected. Descriptive statistics are reported with Fisher's exact test or a chi-squared test, as appropriate, and multivariable conditional logistic regression was conducted. RESULTS: Our study included 352 cases with VUE and 657 controls. A diagnosis of gestational diabetes (p = 0.03) and gestational hypertension (p = 0.06) was 1.5 times more likely to occur in those with a VUE diagnosis. A trend was also seen for chronic hypertension (odds ratio [OR] = 1.7, p = 0.07) and preeclampsia (OR = 1.5, p = 0.09) compared with controls. Placentas with VUE, specifically high-grade VUE, were more likely to be small for gestational age (p = 0.01), and to be diagnosed with other placental findings including lymphoplasmacytic or chronic deciduitis (p < 0.01), maternal (p < 0.01) and fetal vascular malperfusion (p = 0.02), and chorionitis (acute or chronic; p < 0.01). CONCLUSION: Gestational diabetes and hypertension were associated with a diagnosis of VUE, and overall, VUE placentas have more abnormal placental findings compared with control. Understanding VUE risk factors may facilitate prenatal care strategies and counseling to achieve the best outcomes for pregnant patients and their neonates. KEY POINTS: · VUE is a common inflammatory lesion of the placenta.. · Gestational diabetes and hypertension are associated with a VUE diagnosis.. · Findings of other placental pathologies increase in VUE..
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OBJECTIVES: There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs. METHODS: A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated. RESULTS: This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease. CONCLUSIONS: High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.
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Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Pene , Masculino , Humanos , Antígeno B7-H1/metabolismo , Nectinas , Infecciones por Papillomavirus/complicaciones , Carcinoma de Células Escamosas/metabolismo , Biomarcadores , Neoplasias del Pene/cirugía , Neoplasias del Pene/patología , Biomarcadores de Tumor/metabolismoRESUMEN
IMPORTANCE: We analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission "sinks." In addition, major policies, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, did not appear to have an impact on virus diversity across individual counties.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Minnesota/epidemiología , Pandemias , COVID-19/epidemiología , Control de Enfermedades Transmisibles , GenómicaRESUMEN
Sequencing is increasingly used for infective endocarditis (IE) diagnosis. Here, the performance of 16S rRNA gene PCR/sequencing of heart valves utilized in routine clinical practice was compared with conventional IE diagnostics. Subjects whose heart valves were sent to the clinical microbiology laboratory for 16S rRNA gene PCR/sequencing from August 2020 through February 2022 were studied. A PCR assay targeting V1 to V3 regions of the 16S rRNA gene was performed, followed by Sanger and/or next-generation sequencing (NGS) (using an Illumina MiSeq), or reported as negative, depending on an algorithm that included the PCR cycle threshold value. Fifty-four subjects, including 40 with IE, three with cured IE, and 11 with noninfective valvular disease, were studied. Thirty-one positive results, 11 from NGS and 20 from Sanger sequencing, were generated from analysis of 16S rRNA gene sequence(s). Positivity rates of blood cultures and 16S rRNA gene PCR/sequencing of valves were 55% and 75%, respectively (P = 0.06). In those with prior antibiotic exposure, positivity rates of blood cultures and 16S rRNA gene PCR/sequencing of valves were 11% and 76%, respectively (P < 0.001). Overall, 61% of blood culture-negative IE subjects had positive valve 16S rRNA gene PCR/sequencing results. 16S rRNA gene-based PCR/sequencing of heart valves is a useful diagnostic tool for pathogen identification in patients with blood culture-negative IE undergoing valve surgery in routine clinical practice.
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Endocarditis Bacteriana , Endocarditis , Humanos , ARN Ribosómico 16S/genética , Genes de ARNr , Análisis de Secuencia de ADN/métodos , ADN Bacteriano/genética , ADN Bacteriano/análisis , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/microbiología , Válvulas Cardíacas/microbiología , Endocarditis/diagnóstico , Endocarditis/microbiología , Reacción en Cadena de la Polimerasa/métodosRESUMEN
In this report, we describe a case of septic arthritis caused by the newly described Mycobacterium persicum (formerly Mycobacterium kansasii complex). The patient's only significant exposure was home gardening. To our knowledge, this represents the first documented case of M. persicum infection in the United States and first septic arthritis.
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BACKGROUND: Focal-occult placenta accreta spectrum is known to cause adverse obstetrical morbidity outcomes, however, direct comparisons with previa-associated placenta accreta spectrum morbidity are lacking. OBJECTIVE: We sought to compare the baseline characteristics, surgical and obstetrical morbidity, and subsequent pregnancy outcomes of patients with focal-occult placenta accreta spectrum with those of patients with previa-associated accreta. STUDY DESIGN: A retrospective review was conducted of all pathologically confirmed placenta accreta spectrum cases from 2018 to 2022 at a tertiary care center. The baseline characteristics, surgical, obstetrical, and subsequent pregnancy outcomes were recorded. Cases of focal-occult placenta accreta spectrum was compared with cases of previa-associated placenta accreta spectrum across a range of morbidity characteristics including hemorrhagic factors, interventions, postdelivery reoperations, infections, and intensive care unit admission. Statistical comparison was performed using Kruskal-Wallis or chi-square tests, and a P value of <.05 was considered significant. RESULTS: A total of 74 cases were identified with 43 focal-occult and 31 previa-associated placenta accreta spectrum cases. Of those, 25.6% of the patients with focal-occult placenta accreta spectrum and 100% of the patients with previa-associated placenta accreta spectrum underwent a hysterectomy. One case of focal-occult placenta accreta spectrum and 29 cases of previa-associated placenta accreta spectrum were diagnosed antenatally. Patients with focal-occult placenta accreta spectrum did not differ from those with previa-associated placenta accreta spectrum in mean maternal age (33.0 vs 33.1 years), body mass index, or the incidence of previous dilation and curettage procedures (16.3% vs 25.8%). Patients with focal-occult placenta accreta spectrum were significantly more likely to have a lower mean parity (1.5 vs 3.6 gestations), higher gestational age at delivery (36.1 vs 33.9 weeks' gestation), and were less likely to have had a previous cesarean delivery (12/43, 27.9% vs 30/31, 96.8%). In addition, patients with focal-occult placenta accreta spectrum had less previous cesarean deliveries (mean, 0.5 vs 2.3), were more likely to have undergone in vitro fertilization (20.9% vs 3.2%), and less likely to have anterior placentation. When contrasting the clinical outcomes of patients with focal-occult placenta accreta spectrum with those with previa-associated placenta accreta spectrum, the postpartum hemorrhage rates (71.0% vs 67.4%), mean quantitative blood loss (2099 mL; range, 500-9516 mL vs 2119 mL; range 350-12,220 mL), mean units of red blood cells transfused (1.4 vs 1.7), massive transfusion rate (9.3% vs 3.2%), and intensive care unit admission rates (11.6% vs 6.5%) were not significantly different, but there was a nonsignificant trend toward higher morbidity among patients with focal-occult accreta. Patients with focal-occult accreta had a higher incidence of reoperations or return to the operating room (30.2 vs 6.5%; P=.01). When comparing focal-occult with previa-associated placenta accreta spectrum, the composite outcomes, including hemorrhagic morbidity (77.4% vs 74.4%), any maternal morbidity (83.9% vs 76.7%), and severe maternal morbidity (64.5% vs 65.1%), were not significantly different between the groups. Nine focal-occult placenta accreta spectrum patients had a subsequent pregnancy, and 3 of those had recurrent placenta accreta spectrum. CONCLUSION: Focal-occult placenta accreta spectrum presents with fewer identifiable risk factors than placenta previa-associated placenta accreta spectrum but may be associated with an in vitro fertilization pregnancy. Patients with focal-occult placenta accreta spectrum was observed to have a higher incidence of reoperation when compared with patients previa-associated placenta accreta spectrum, and no other statistically significant differences in morbidity outcomes were observed. The absence of differences in morbidity outcomes may be attributable to a lack of antenatal detection of focal-occult accreta and merits further investigation.
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Placenta Accreta , Placenta Previa , Embarazo , Humanos , Femenino , Adulto , Lactante , Cesárea/efectos adversos , Placenta Accreta/diagnóstico , Placenta Accreta/epidemiología , Placenta Accreta/cirugía , Estudios Retrospectivos , Histerectomía/métodos , Resultado del Embarazo , Placenta Previa/diagnóstico , Placenta Previa/epidemiología , Placenta Previa/etiologíaRESUMEN
The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these 'surge-associated mutations' (Odds Ratio = 14.19, 95% CI 6.15-32.75, p value = 3.41 × 10-10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85-90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.