Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem ...Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.
ALIF (anterior lumbar interbody fusion) and other spinal fusion surgeries are among the most common orthopaedic procedures requiring blood transfusions. However, blood transfusions have been ...associated with various complications, including adverse reactions and infections. The present study aims to identify independent risk factors for blood transfusions in patients undergoing single-level ALIF specifically to better identify high risk patients and optimize perioperative management.
All patients who had undergone single-level ALIF patients for the treatment of degenerative spinal conditions, excluding traumatic, pathologic, and infectious etiologies, were identified by querying a multi-institutional surgical registry from 2005 to 2018. Multi-level fusions, PLIF/TLIF, and posterior procedures were also excluded. Mann-Whitney-U-Tests were used to analyze continuous variables, while Fisher's-Exact-Tests/Bonferroni-Corrected-Tests were used for categorical variables. Multivariate logistic regression analysis with alternating backward stepwise elimination and forward entry was implemented to identify significant predictors for blood transfusions within 72 hours after incision. The predicted probabilities were used in post-regression diagnostics to generate a Receiver Operating Characteristic (ROC) curve to assess model performance.
4,792 single-level ALIF patients met inclusion criteria - 183 (3.82%) had received blood transfusions within 72 hours after incision and 4,609 (96.18%) had not. Age ≥60 years (OR 1.954, p<0.001), preoperative transfusions (OR 33.758, p=0.023), extended operative times (≥197.0 minutes; 75th percentile) (OR 4.645, p<0.001), ASA≥3 (OR 1.395, p<0.001) and preoperative hematocrit levels (Hct) 30.00-37.99 (OR 1.562, p=0.016) and Hct <30.00 (OR 6.334, p<0.001) were shown to be significant independent risk factors for perioperative blood transfusions. The area under the ROC curve (AUROC; C-statistic) was 0.759 (p<0.001), indicating relatively strong discriminatory ability/predictability of the final model.
Several independent risk factors including age ≥60 years, preoperative blood transfusions and extended operative times increased risk for blood transfusion following single-level ALIF. The present study aims to help surgeons identify high-risk patients to better communicate postoperative expectations and optimize patients to reduce the risk of transfusions and secondary complications.
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Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory ...syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 COVID-19; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range IQR, 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.
•sC5b9 plasma levels are elevated in children with SARS-CoV-2 infection, even if they have minimal symptoms of COVID-19.•A high proportion of children with SARS-CoV-2 infection met clinical criteria for TMA.
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Significant gaps remain in understanding the response of plant reproduction to environmental change. This is partly because measuring reproduction in long‐lived plants requires direct observation ...over many years and such datasets have rarely been made publicly available. Here we introduce MASTREE+, a data set that collates reproductive time‐series data from across the globe and makes these data freely available to the community. MASTREE+ includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations worldwide. These observations consist of 5971 population‐level time‐series from 974 species in 66 countries. The mean and median time‐series length is 12.4 and 10 years respectively, and the data set includes 1122 series that extend over at least two decades (≥20 years of observations). For a subset of well‐studied species, MASTREE+ includes extensive replication of time‐series across geographical and climatic gradients. Here we describe the open‐access data set, available as a.csv file, and we introduce an associated web‐based app for data exploration. MASTREE+ will provide the basis for improved understanding of the response of long‐lived plant reproduction to environmental change. Additionally, MASTREE+ will enable investigation of the ecology and evolution of reproductive strategies in perennial plants, and the role of plant reproduction as a driver of ecosystem dynamics.
Resumen
Aún existen importantes vacíos en la comprensión de la respuesta reproductiva de las plantas al cambio medioambiental, en parte, porque su monitoreo en especies de plantas longevas requiere una observación directa durante muchos años, y estos conjuntos de datos rara vez han estado disponibles. Aquí presentamos a MASTREE +, una base de datos que recopila series de tiempo de la reproducción de las plantas de todo el planeta, poniendo a disposición estos datos de libre acceso para la comunidad científica. MASTREE + incluye 73.828 puntos de observación de la reproducción anual georreferenciados (ej. conteos de semillas y frutos) en poblaciones de plantas perennes en todo el mundo. Estas observaciones consisten en 5971 series temporales a nivel de población provenientes de 974 especies en 66 países. La mediana de la duración de las series de tiempo es de 10 años (media = 12.4 años) y el conjunto de datos incluye 1.122 series de al menos dos décadas (≥20 años de observaciones). Para un subconjunto de especies bien estudiadas, MASTREE +incluye un amplio conjunto de series temporales replicadas en gradientes geográficos y climáticos. Describimos el conjunto de datos de acceso abierto disponible como un archivo.csv y presentamos una aplicación web asociada para la exploración de datos. MASTREE+ proporcionará la base para mejorar la comprensión sobre la respuesta reproductiva de plantas longevas al cambio medioambiental. Además, MASTREE+ facilitará los avances en la investigación de la ecología y la evolución de las estrategias reproductivas en plantas perennes y el papel de la reproducción vegetal como determinante de la dinámica de ecosistemas.
MASTREE+ is an open‐access data set that collates reproductive time‐series data from across the globe. It includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations, consisting of 5,971 population‐level time‐series from 974 species. MASTREE+ will provide the basis for improved understanding of the response of plant reproduction to environmental change and can be used to investigate the ecology and evolution of plant reproductive strategies and the role of plant reproduction as a driver of ecosystem dynamics.
Isopropylated and
-butylated triarylphosphate esters (ITPs and TBPPs, respectively) are plasticizers and flame retardants that are ubiquitous in indoor environments; however, no studies to date have ...characterized their metabolism. Using human liver subcellular S9 fractions, phase I and II
metabolism of triphenyl phosphate (TPHP), 4-
-butylphenyl diphenyl phosphate (4tBPDPP), 2-isopropylphenyl diphenyl phosphate (2IPPDPP), and 4-isopropylphenyl diphenyl phosphate (4IPPDPP) was investigated at 1 and 10 μM doses. Parent depletion and the formation of known or suspected metabolites (e.g., likely hydrolysis or hydroxylated products), including diphenyl phosphate (DPHP), hydroxyl-triphenyl phosphate (OH-TPHP), isopropylphenyl phenyl phosphate (ip-PPP), and
-butylphenyl phenyl phosphate (tb-PPP), were monitored and quantified via GC/MS or LC-MS/MS. tb-PPP and its conjugates were identified as the major
metabolites of 4tBPDPP and accounted for 71% and 49%, respectively, of the parent molecule that was metabolized during the incubation. While the mass balance between parents and metabolites was conserved for TPHP and 4tBPDPP, approximately 20% of the initial parent mass was unaccounted for after quantifying suspected metabolites of 2IPPDPP and 4IPPDPP that had authentic standards available. Two novel ITP metabolites, mono-isopropenylphenyl diphenyl phosphate and hydroxy-isopropylphenyl diphenyl phosphate, were tentatively identified by high-resolution mass spectrometry and screened for in recently collected human urine where mono-isopropenylphenyl diphenyl phosphate was detected in one of nine samples analyzed. This study provides insight into the biological fate of ITP and TBPP isomers in human tissues and is useful in identifying appropriate biomarkers of exposure to monitor, particularly in support of epidemiological studies.
The objective of our study was to assess the utility of targeted breast ultrasound and mammography in evaluating palpable lumps in the mastectomy bed.
This retrospective study identified ...postmastectomy patients who presented for initial imaging evaluation of palpable lumps between January 2009 and December 2015. Clinical, imaging, and pathology results were reviewed. Surgical reconstruction type and percutaneous sampling data were collected. Patients were excluded if they had known malignancy at imaging presentation, if the palpable lump was not at the mastectomy site, or if there was less than 1 year clinical or imaging follow-up in the absence of biopsy. Each palpable site was assigned as a case, and analyses were performed at the case level.
Among the 101 patients with a history of prophylactic or therapeutic mastectomy who presented during the study period, 118 palpable cases met the inclusion criteria. All 118 cases were evaluated with ultrasound and 43 with mammography. Among the 75 cases evaluated with ultrasound alone, nine cancers were detected. Among the 43 cases evaluated with both ultrasound and mammography, three cancers were sonographically detected, of which two were mammographically visible and one was mammographically occult. There were two false-negative ultrasound cases; both underwent sampling because of the level of clinical suspicion. In total, 14 palpable lumps in 12 patients were malignant, and 104 palpable lumps in 89 patients were nonmalignant. Targeted ultrasound yielded a negative predictive value (NPV) of 97% and a positive predictive value 2 of 27%.
Our data suggest that targeted breast ultrasound, with its high NPV, should be the initial imaging test of choice for palpable lumps after mastectomy. Mammography yielded no additional cancers but was helpful in confirming benign diagnoses. The two false-negative ultrasound cases support palpation-guided sampling for imaging-occult and clinically suspicious palpable lumps.
Abstract A range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk ...(ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07–7.90, p = 5.31 × 10 −11 ). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.
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