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Outcomes of pediatric patients who received extracorporeal life support (ECLS) for COVID-19 remain poorly described. The aim of this multi-institutional retrospective observational study was to evaluate these outcomes and assess for prognostic factors associated with in-hospital mortality. Seventy-nine patients at 14 pediatric centers across the United States who received ECLS support for COVID-19 infections between January 2020 and July 2022 were included for analysis. Data were extracted from the electronic medical record. The median age was 14.5 years (interquartile range [IQR]: 2–17 years). Most patients were female (54.4%) and had at least one pre-existing comorbidity (84.8%), such as obesity (44.3%, median body mass index percentile: 97% [IQR: 67.5–99.0%]). Venovenous (VV) ECLS was initiated in 50.6% of patients. Median duration of ECLS was 12 days (IQR: 6.0–22.5 days) with a mean duration from admission to ECLS initiation of 5.2 ± 6.3 days. Survival to hospital discharge was 54.4%. Neurological deficits were reported in 16.3% of survivors. Nonsurvivors were of older age (13.3 ± 6.2 years vs.9.3 ± 7.7 years, p = 0.012), more likely to receive renal replacement therapy (63.9% vs.30.2%, p = 0.003), demonstrated longer durations from admission to ECLS initiation (7.0 ± 8.1 days vs.3.7 ± 3.8 days, p = 0.030), and had higher rates of ECLS-related complications (91.7% vs.69.8%, p = 0.016) than survivors. Pediatric patients with COVID-19 who received ECLS demonstrated substantial morbidity and further investigation is warranted to optimize management strategies.

Fast evolution of the Internet, mobile technologies and energy efficient communication protocols has given a new momentum to e-businesses and world become a global village. Due to increase in the usage of internet and number of mobile users, many companies use these channels to make their products and brands visible to their customers all over the world. Although, some progress has been made towards this direction but further exploration is required, particularly it is still a challenge to enhance in-flight passengers’ shopping experience through efficient and reliable communication protocols. In this paper, we proposed a framework for omni-channel which is based on cognitive radio and machine learning. The proposed cognitive radio communication protocols provide seamless connectivity to in-flight passengers through energy efficient mode like machine learning (ML). Here, machine learning helps to develop user profile, based on relevance feedback that address the problem of catalogue and information overload. In this paper, we also discuss various challenges and opportunities associated with the proposed omni-channel business model. Moreover, the role and impact of emerging technologies such as cognitive radio and 5G in realizing omni-channel businesses is discussed in this paper. Our results explain the seamless communication between aircraft users and merchandise, through reliable and efficient connectivity when the aircraft passes over different geographic areas i.e. urban/rural land or sea at different altitudes and geographic locations. Here, backup data channel is introduced which further enhance the reliability of connection especially when primary users turns ON during the communication. Furthermore, the proposed model helps to reduce communication time and consume less energy to transmit with high throughput as compared to the benchmark cognitive radio protocols.

We present a method for hyperspectral pixel unmixing. The proposed method assumes that 1) abundances can be encoded as Dirichlet distributions and 2) spectra of endmembers can be represented as multivariate normal distributions. The method solves the problem of abundance estimation and endmember extraction within a variational autoencoder setting where a Dirichlet bottleneck layer models the abundances, and the decoder performs endmember extraction. The proposed method can also leverage the transfer learning paradigm, where the model is only trained on synthetic data containing pixels that are linear combinations of one or more endmembers of interest. In this case, we retrieve endmembers (spectra) from the United States Geological Survey Spectral Library. The model thus trained can be subsequently used to perform pixel unmixing on “real data” that contains a subset of the endmembers used to generate the synthetic data. The model achieves state-of-the-art results on several benchmarks: Cuprite, Urban Hydice, and Samson. We also present a new synthetic dataset, OnTech-HSI-Syn-21, that can be used to study hyperspectral pixel unmixing methods. We showcase the transfer learning capabilities of the proposed model on Cuprite and OnTech-HSI-Syn-21 datasets. In summary, the proposed method can be applied for pixel unmixing in a variety of domains, including agriculture, forestry, mineralogy, analysis of materials, and healthcare. In addition, the proposed method eschews the need for labeled data for training by leveraging the transfer learning paradigm, where the model is trained on synthetic data generated using the endmembers present in the “real” data.

IMPORTANCE: There is variability in practice and imaging usage to diagnose cervical spine injury (CSI) following blunt trauma in pediatric patients. OBJECTIVE: To develop a prediction model to guide imaging usage and to identify trends in imaging and to evaluate the PEDSPINE model. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included pediatric patients (<3 years years) following blunt trauma between January 2007 and July 2017. Of 22 centers in PEDSPINE, 15 centers, comprising level 1 and 2 stand-alone pediatric hospitals, level 1 and 2 pediatric hospitals within an adult hospital, and level 1 adult hospitals, were included. Patients who died prior to obtaining cervical spine imaging were excluded. Descriptive analysis was performed to describe the population, use of imaging, and injury patterns. PEDSPINE model validation was performed. A new algorithm was derived using clinical criteria and formulation of a multiclass classification problem. Analysis took place from January to October 2022. EXPOSURE: Blunt trauma. MAIN OUTCOMES AND MEASURES: Primary outcome was CSI. The primary and secondary objectives were predetermined. RESULTS: The current study, PEDSPINE II, included 9389 patients, of which 128 (1.36%) had CSI, twice the rate in PEDSPINE (0.66%). The mean (SD) age was 1.3 (0.9) years; and 70 patients (54.7%) were male. Overall, 7113 children (80%) underwent cervical spine imaging, compared with 7882 (63%) in PEDSPINE. Several candidate models were fitted for the multiclass classification problem. After comparative analysis, the multinomial regression model was chosen with one-vs-rest area under the curve (AUC) of 0.903 (95% CI, 0.836-0.943) and was able to discriminate between bony and ligamentous injury. PEDSPINE and PEDSPINE II models’ ability to identify CSI were compared. In predicting the presence of any injury, PEDSPINE II obtained a one-vs-rest AUC of 0.885 (95% CI, 0.804-0.934), outperforming the PEDSPINE score (AUC, 0.845; 95% CI, 0.769-0.915). CONCLUSION AND RELEVANCE: This study found wide clinical variability in the evaluation of pediatric trauma patients with increased use of cervical spine imaging. This has implications of increased cost, increased radiation exposure, and a potential for overdiagnosis. This prediction tool could help to decrease the use of imaging, aid in clinical decision-making, and decrease hospital resource use and cost.

ObjectivesStudies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC.MethodsA comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Qtest and I2statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed.ResultsSeven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable.ConclusionMetformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations.PROSPERO registration numberCRD42021237127.

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The high level of lithium storage in synthetic porous carbons has necessitated the development of accurate models for estimating the specific capacity of carbon-based lithium-ion battery (LIB) anodes. To date, various models have been developed to estimate the storage capacity of lithium in carbonaceous materials. However, these models are complex and do not take into account the effect of porosity in their estimations. In this paper, a novel model is proposed to predict the specific capacity of porous carbon LIB anodes. For this purpose, a new factor is introduced, which is called normalized surface area. Considering this factor, the contribution of surface lithium storage can be added to the lithium stored in the bulk to have a better prediction. The novel model proposed in this study is able to estimate the lithium storage capacity of LIB anodes based on the porosity of porous carbons for the first time. Benefiting porosity value (specific surface area) makes the predictions quick, facile, and sensible for the scientists and experts designing LIBs using porous carbon anodes. The predicted capacities were compared with that of the literature reported by experimental works. The remarkable consistency of the measured and predicted capacities of the LIB anodes also confirms the validity of the approach and its reliability for further predictions.

Sequential urine analysis in the womb may accurately diagnose fetal obstructive uropathy, a condition where urine cannot flow freely. Such blockage often damages the normal functioning of the kidney. Researchers examined the urine of 29 male fetuses with obstructive uropathy at least trice. The last urine samples predicted severe kidney damage more accurately than initial analysis. Bladder shunts were installed in 14 fetuses whose urine results improved during multiple testing, indicating less severe kidney problems. Ten children who survived more than two years after shunt surgery were considered good outcomes. One additional marginal case improved only after kidney transplantation at age 3. Three shunt recipients had poor prognosis due to massive kidney damage and died after birth. The remaining 15 pregnancies were terminated following a diagnosis of marked kidney damage. Autopsies of fetuses with serious kidney problems indicated by earlier urine diagnosis confirmed abnormal tissue development in the kidney.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

It is a generally held concept that finding increased aspirated amniotic fluid squames at autopsy supports a diagnosis of acute fetal asphyxia, the massive aspiration of squames being an indicator of terminal gasping. To evaluate this concept, we identified autopsies on 15 third-trimester stillborns with clinical acute placental abruption (acute asphyxia); 13 also had thymic petechiae and none had severe acute thymic involution, findings also supporting acute asphyxia. Thirty third-trimester stillborns with findings supporting a subacute or chronic mode of death, including severe thymic involution and absence of thymic petechiae, comprised the comparison group. Intra-alveolar squames were scored as 0, no squames; 1+, scattered squames singly or in small groups; and 2+, squames in many alveoli, at least focally in compacted clusters. In all cases, the squames were patchily distributed, and none received a score of 0. In the abruption group, the intra-alveolar squames were scored as 1+ in 12 (80%) and as 2+ in 3 (20%) cases, while in the comparison group, the squames were scored as 1+ in 20 (67%) and 2+ in 10 (33%) cases (P= NS). There was also no difference in the quantification of intra-alveolar squames in term compared to preterm stillborns. In conclusion, quantification of intra-alveolar squames did not aid in separating an acute mode of death (acute asphyxia) from subacute or chronic modes of death.

Skeletal ciliopathies comprise a spectrum of ciliary malfunction disorders that have a profound effect on the skeleton. Most common among these disorders is short rib polydactyly syndrome (SRPS), a recessively inherited perinatal lethal condition characterized by a long narrow chest, markedly shortened long bones, polydactyly and, often, multi-organ system involvement. SRPS shows extensive locus heterogeneity with mutations in genes encoding proteins that participate in cilia formation and/or function. Herein we describe mutations in IFT43, a satellite member of the retrograde IFT-A complex, that produce a form of SRPS with unusual bending of the ribs and appendicular bones. These newly described IFT43mutations disrupted cilia formation, produced abnormalities in cartilage growth plate architecture thus contributing to altered endochondral ossification. We further show that the IFT43SRPS phenotype is similar to SRPS resulting from mutations in the gene encoding IFT121 (WDR35), a direct interactor with IFT43. This study defines a new IFT43-associated phenotype, identifying an additional locus for SRPS. The data demonstrate that IFT43 is essential for ciliogenesis and that the mutations disrupted the orderly proliferation and differentiation of growth plate chondrocytes, resulting in a severe effect on endochondral ossification and mineralization. Phenotypic similarities with SRPS cases resulting from mutations in the gene encoding the IFT43 direct interacting protein IFT121 suggests that similar mechanisms may be disrupted by defects in these two IFT-A satellite interactors.

Adrenal histologic changes, including compact cell change (CCC), cystic change (CYC), and adrenal hemorrhage (AH), and their clinical correlations have only infrequently been investigated in stillbirth. We evaluated 75 third trimester singleton stillborns with complete autopsies (30 term and 45 preterm). A total of 58 had unexplained stillbirth and 17 had clinical placental abruption. The mothers were predominantly African-American (89%). CCC and CYC were diagnosed as cytoplasmic eosinophilia and cystic cavities in the definitive cortex, respectively. Adrenal changes were correlated with acute thymic involution (ATI), thymic petechiae, and clinical features, including abruption. CCC, CYC, and AH were present in 58 (77%), 51 (68%), and 15 (20%) of the 75 stillborns, respectively. CCC and CYC were frequently seen together (P?

Measurement of differential elastic cross section of protons from aluminum was taken at 165° degree in the 2.4–4.8 MeV energy range. The results and measured energy resonances were compared with reported measurements. These data will improve the reliability of backscattering analysis of Al with protons in this energy region.

Many 3rd-trimester stillbirths are unexplained, including the time course of the illness. Histologic acute thymic involution (ATI), when graded, correlates with duration of acute illness (grade 0, <12 hours; grade 4, >72 hours). Histologic brain injury is also common in stillbirth. We investigated ATI in unexplained stillbirth and correlated it with neuropathologic injury by identifying 58 autopsies of unexplained, 3rd-trimester stillborns (preterm, n =24; term, n =34) that included brain examination and graded ATI from 0 (resting state) to 4 (pronounced lymphodepletion). Gray matter injury (GMI) and white matter injury (WMI) were classified as older, recent, or absent, and ATI was correlated with GMI, WMI, thymic weight, and clinical data. Nine cases (16%) had ATI grade 0–1; 19 (33%), grade 2; 24 (41%), grade 3; and 6 (10%), grade 4. Older GMI and WMI were present in 39 (67%) and 10 (17%) stillborns, respectively. Higher ATI grade correlated significantly with older GMI (P <0.001) and WMI (P =0.014). The ATI grade was higher in the small-for-gestational stillborns compared with the appropriate- or large-for-gestational stillborns (P =0.017) but did not correlate significantly with gestational age or other clinical or demographic factors evaluated. The ATI grades 2–4 were found in 84% of the stillborns, consistent with onset of acute illness between 24 and >72 hours before demise. Higher ATI grade correlated significantly with older brain injury, suggesting similar time of onset and shared underlying pathophysiologic events, the specific nature of which remains unclear.

In adults, the association between obesity and obstructive sleep apnea (OSA) is established, and many are concerned OSA increases surgical risk. Pre-operative screening for OSA is standard, and this is also the case in adolescent bariatric surgery. We noted many of our patients were without significant OSA, despite being obese. We reviewed our experience with screening polysomnography (PSG) to determine any predictive variables or complications. All bariatric surgery patients from our hospital who had undergone PSG were included, and were stratified into ‘OSA’ or ‘no OSA’ by obstructive apnea-hypopnea index (OAHI), as well as by sex. A total of 49 adolescents enrolled during the study period: 10 males and 39 females. OSA prevalence was 42.9 %; males 80 %, females 33.3 %. Height, weight, body mass index (BMI), and prevalence of hypertension were significantly higher in patients with OSA. By sex, females also had more metabolic syndrome and witnessed apneas, while only weight and BMI remained significant in males. There were no peri-operative complications. Despite uniform obesity, less than half our adolescents had significant OSA on PSG. As no modeling exists to predict OSA in morbidly obese adolescents, we continue to recommend routine PSG, especially in higher weight and BMI patients, and those with hypertension.

The purpose of this study was to delineate the epidemiology of pediatric firearm injuries, including ethno-demographic patterns with impact on years of potential life lost (YPLL). A 2-year review of the National Trauma Data Bank (2007 to 2008) was conducted. Firearm fatalities in records of patients younger than 18 years were identified. Data were analyzed by demographic and injury characteristics and YPLL was calculated by ethnicity. A total of 577 deaths were identified in the pediatric group. Blacks accounted for 49.7 per cent of the fatalities; Hispanics, 19.2 per cent; whites, 17.7 per cent, and other ethnicity, 13.4 per cent. Median Injury Severity Score was 25 with a median Glasgow Coma Scale score of 3. Traumatic brain injury was present in 84.2 per cent of the records. Assault accounted for 72.8 per cent, self-inflicted injury 12.7 per cent, and unintentional injuries were 8.2 per cent. Most firearm fatalities occurred at home (33.6%). By emergency department (ED) disposition, 29.3 per cent died in the ED, 32.9 per cent were admitted to the intensive care unit, and 30.0 per cent taken to the operating room. Blacks had a total of 17,446 YPLL, Hispanics 6,776 YPLL, and whites 6,718 YPLL. Pediatric firearm fatalities still remain an important public health concern. Inclusive gun control policies focused on primary prevention of accidental injuries may be more effective in mitigating its impact.

Recent advances in camera hardware, processing capabilities, storage capacities, and communication technologies suggest an evolution of traditional multi-camera systems into networks of highly capable computational and smart cameras. These networks can be seen as visual sensor nodes that combine sensing with onboard processing and storage, and that are able to communicate with other similar sensors in the vicinity. As a future development step, these visual sensor nodes will have the necessary control and coordination machinery to set up ad-hoc sensing networks, capable of capturing, analyzing, and storing large amounts of image and video data over extended spaces to support a variety of applications. Opportunities for application development abound in domains as diverse as smart environments, wearable sensing, security and surveillance, environmental monitoring and disaster response, traffic management and urban sensing, elderly care and wellness monitoring, geo-scale monitoring, etc. These networks must also exhibit a great deal of autonomy as the sheer scale of the networks and the tremendous amount of data present in them render human-in-the-loop operation for the most part infeasible. Much work is still needed to realize this vision of ad-hoc networks of computational and smart cameras capable of providing perceptive coverage of wide areas with little or no human supervision. The goal of this special issue is to bring together papers dealing with various aspects of this vision.

We report the neuropathologic findings and clinicopathologic associations in 63 3rd trimester singleton stillborn fetuses. All were =28 weeks estimated gestational age (EGA) with complete autopsies, including placental examination. Fetuses with chromosomal abnormalities, major congenital anomalies, and intrapartum demise were excluded. The cases were divided into those with abruption (n= 12) and those with unexplained fetal demise (n= 51). The latter group was then subdivided by gestational age with 3 subgroups (preterm 28 to <32 weeks EGA (n= 16), preterm 32 to <37 weeks EGA (n= 13), and term 37–41 weeks EGA (n= 22). Each group was further subdivided as appropriate-for-gestational age/large-for-gestational age (AGA/LGA) or small-for-gestational age (SGA). Placental lesions were also evaluated and correlated with brain lesions.Established or recent injury involving gray or white matter was seen in 88% of the fetuses with unexplained demise versus 42% with abruption (P= 0.001). The most common form of brain injury was established gray matter damage, seen in 65% of the fetuses with unexplained demise versus 25% with abruption (P= 0.021), the most common pattern being established pontosubicular neuronal necrosis plus established neuronal necrosis in other sites. There was no significant difference in the frequency of brain injury between the SGA fetuses and AGA/LGA fetuses or between the unexplained stillbirth preterm and term subgroups, and there was no unequivocal correlation between placental lesions and brain lesions. Brain injury, most frequently established gray matter damage, is seen in the majority of stillborn infants with unexplained demise, indicating that the brain injury predates the period immediately before death.

Over the last two decades, the prevalence of obesity in children ages 6 to 11 years has almost tripled, and more than tripled in teenagers. The purpose of this study is to define the characteristics of hospitalized obese children and utilization of bariatric surgery. Analysis of the 1998 to 2007 Healthcare Cost and Utilization Project Nationwide Inpatient Sample was conducted with years 2000, 2003, and 2006 substituted with the Kids’ Inpatient Database dataset. Records with diagnosis of obesity were included in the analysis with major comorbidities defined as the presence of hypertension, obstructive sleep apnea, diabetes mellitus, or coronary artery disease. National estimates over a 10-year period were calculated using sampling weights. Approximately 223,700 children met the inclusion criteria, of which 20 per cent were morbidly obese, with an overall 20 per cent incidence of major comorbidity. Comorbidities were found to be significantly higher among Asian/Pacific Islander (28.3%), African-American (27.2%), and Hispanic (19.1%; P< 0.001) compared with white (15.6%) children. Only 2 per cent of morbidly obese children with major comorbidity underwent a bariatric procedure. Obesity remains a growing childhood epidemic with a disproportionate ethnic burden of comorbidities. Bariatric surgery remains a viable option and a structured guideline in children may provide equitable access across different ethnic and socioeconomic groups.

We report 51 placentas diagnosed with eosinophilic/T-cell chorionic vasculitis (E/TCV), an unusual form of chorionic vasculitis characterized by an infiltrate composed predominantly of CD3+ T cells and eosinophils. The placentas were all 3rd trimester, with 48 (94.1%) being term. Forty-seven (92.2%) were singleton placentas, and the remaining 4 were twins. The E/TCV was limited to 1 chorionic surface vessel in 40 (78.4%) and involved 50% or less of the vessel circumference in 30 (58.8%) placentas. The inflammation faced the intervillous space in 12 (23.5%) and the amniotic cavity in 8 (15.7%) and had no distinct predominant direction in the remaining 31 (60.8%) placentas. Twelve (25.5%) placentas showed mural thrombi or intramural fibrin in association with the E/TCV. One hundred six term singleton placentas were selected as the control group, and the 47 singleton placentas with E/TCV made up the study group for comparison of demographic and histopathologic features. Villitis of unknown etiology was identified more frequently in study group placentas (20 [42.6%]) compared with control group placentas (14 [13.2%]) (P< 0.001). Vascular changes of fetal vascular thrombo-occlusive disease were identified away from the E/TCV more frequently in study group placentas (8 [17.0%]) compared with control group placentas (4 [3.8%]) (P= 0.008). There were no significant differences in the frequencies of other placental lesions studied, including acute inflammatory lesions and lesions related to maternal underperfusion. There were no significant differences in maternal age, race, parity, birth weight, allergy history, blood type, or medication use.

Hollow viscus injuries (HVI) are uncommon after blunt trauma, and accomplishing a timely diagnosis can be difficult. Time to operative intervention has been implicated as a risk factor for mortality, but reports are conflicting.

Abstract: We present a surveillance system, comprising wide field-of-view (FOV) passive cameras and pan/tilt/zoom (PTZ) active cameras, which automatically captures high-resolution videos of pedestrians as they move through a designated area. A wide-FOV static camera can track multiple pedestrians, while any PTZ active camera can capture high-quality videos of one pedestrian at a time. We formulate the multi-camera control strategy as an online scheduling problem and propose a solution that combines the information gathered by the wide-FOV cameras with weighted round-robin scheduling to guide the available PTZ cameras, such that each pedestrian is observed by at least one PTZ camera while in the designated area. A centerpiece of our work is the development and testing of experimental surveillance systems within a visually and behaviorally realistic virtual environment simulator. The simulator is valuable as our research would be more or less infeasible in the real world given the impediments to deploying and experimenting with appropriately complex camera sensor networks in large public spaces. In particular, we demonstrate our surveillance system in a virtual train station environment populated by autonomous, lifelike virtual pedestrians, wherein easily reconfigurable virtual cameras generate synthetic video feeds. The video streams emulate those generated by real surveillance cameras monitoring richly populated public spaces.

Maintenance of enterocyte activity during extracellular acidosis requires functional sodium/proton exchangers (NHE), which are present at both basolateral and apical surfaces. Necrotizing enterocolitis is characterized by systemic hypoperfusion, metabolic acidosis, and the apical to basolateral translocation of endotoxin (lipopolysaccharide [LPS]). We hypothesized that LPS differentially impairs NHE activity at the basolateral or apical domains of enterocytes, leading to cellular acidification, and explored the mechanisms involved.

Necrotizing enterocolitis (NEC) occurs only after bacterial colonization of the intestine, suggesting that bacterial products, including lipopolysaccharide (endotoxin,) interact with enterocytes in the pathogenesis of this disease. Inflammatory molecules such as cyclooxygenase-2 (COX-2) are important mediators of the septic response leading to NEC. We therefore hypothesized that endotoxin activates production of COX-2 in enterocytes and explored the relative contributions of known mitogen-activated protein kinases (MAPK) pathways in this process.

Histologic inflammation of placenta has been associated with increased risk for bronchopulmonary dysplasia and periventricular leukomalacia among preterm infants. Tumor necrosis factor-a (TNF-a) plays a central role in the regulation of inflammation. Some alleles of TNF (LT-a+250, TNF-a-308, and TNF-a -238) have been associated with susceptibility and/or severity of many diseases characterized by inflammation and/or involving the immune system. To determine whether alleles of TNF-a affect the risk and/or the severity of chorioamnionitis, we examined the placentas of 101 preterm births (birth weight =1250 g) for the presence of inflammation. Maternal and fetal chorioam-nionitis (MCA and FCA, respectively) were graded for severity and staged for location of inflammatory infiltrate. Analysis for TNF-a alleles was done using PCR-restriction fragment length polymorphism technique on DNA extracted from infants' whole blood. MCA and FCA were seen in 45 and 38 placentas, respectively (p = 0.64). Genotypes of TNF-a -308 did not affect the development or the severity of placental inflammation. However, the AA genotype of LT-a+250 occurred more often when MCA and FCA were present compared with placentas without inflammation (p = 0.016 and p = 0.007, respectively). The GA genotype of TNF-a -238 was more common in placentas with severe MCA than with mild MCA (p = 0.015). The number of A alleles of LT-a+250 (GG = 0, GA = 1, AA = 2) correlated directly and significantly with grades and stages of MCA and FCA (p < 0.05). The AA genotype of LT-a +250 is associated with the development of chorioamnionitis among preterm births. The A allele of LT-a+250 seems to worsen the degree of placental inflammation.

Histologic inflammation of placenta has been associated with increased risk for bronchopulmonary dysplasia and periventricular leukomalacia among preterm infants. Tumor necrosis factor- (TNF-) plays a central role in the regulation of inflammation. Some alleles of TNF (LT-250, TNF-−308, and TNF- −238) have been associated with susceptibility and/or severity of many diseases characterized by inflammation and/or involving the immune system. To determine whether alleles of TNF- affect the risk and/or the severity of chorioamnionitis, we examined the placentas of 101 preterm births (birth weight ≤1250 g) for the presence of inflammation. Maternal and fetal chorioam-nionitis (MCA and FCA, respectively) were graded for severity and staged for location of inflammatory infiltrate. Analysis for TNF- alleles was done using PCR-restriction fragment length polymorphism technique on DNA extracted from infants’ whole blood. MCA and FCA were seen in 45 and 38 placentas, respectively (p0.64). Genotypes of TNF- −308 did not affect the development or the severity of placental inflammation. However, the AA genotype of LT-250 occurred more often when MCA and FCA were present compared with placentas without inflammation (p0.016 and p0.007, respectively). The GA genotype of TNF- −238 was more common in placentas with severe MCA than with mild MCA (p0.015). The number of A alleles of LT-250 (GG 0, GA 1, AA 2) correlated directly and significantly with grades and stages of MCA and FCA (p< 0.05). The AA genotype of LT- 250 is associated with the development of chorioamnionitis among preterm births. The A allele of LT-250 seems to worsen the degree of placental inflammation.

We evaluated apoptosis, proliferation, and p53 and bcl-2 expression in a spectrum of intraepithelial and invasive endocervical glandular lesions currently recognized by the World Health Organization as adenocarcinoma in situ, lesions with atypia “less than adenocarcinoma in situ” (endocervical glandular dysplasia and endocervical glandular atypia), and invasive adenocarcinoma. Aside from nuclear atypia, increased mitotic activity and apoptosis are consistent and closely correlated morphologic features of endocervical adenocarcinoma in situ.Apoptotic bodies and mitotic figures were counted in 32 examples of normal endocervical glands, 35 of endocervical glandular atypia, 30 of endocervical glandular dysplasia, 34 of adenocarcinoma in situ, and 30 of invasive adenocarcinoma. These results were correlated with immunohistochemical staining for MIB1, bcl-2, and p53 performed on 20 examples of each. Mitotic counts, p53 expression, and bcl-2 expression all increased significantly and in proportion to the degree of atypia in the spectrum of endocervical lesions. Apoptotic body counts and MIB1 expression also increased significantly with increasing atypia, but showed higher levels in adenocarcinoma in situthan in invasive adenocarcinoma. Apoptosis correlates with proliferation as measured by mitotic counts and MIB1, and also with p53 and bcl-2 expression. Apoptosis appears to be an important mechanism in the pathogenesis of endocervical glandular lesions and may be useful as an aid in their evaluation and diagnosis.

Clinically responsive placental examination seeks to provide useful information regarding the etiology, prognosis, and recurrence risk of pregnancy disorders. The purpose of this study was to assemble and validate a complete set of the placental reaction patterns seen with amniotic fluid infection in the hope that this might provide a standardized diagnostic framework useful for practicing pathologists. Study cases (14 with amniotic fluid infection, 6 controls) were reviewed blindly by six pathologists after agreement on a standard set of diagnostic criteria. After analysis of initial results, criteria were refined and a second, overlapping set of cases were reviewed. Majority vote served as the gold standard. Grading and staging of maternal and fetal inflammatory responses was found to be more reproducible using a two- versus three-tiered grading system than a three- versus five-tiered staging system (overall agreement 81% vs. 71%). Sensitivity, specificity, and efficiency for individual observations ranged from 67–100% (24/30 > 90%). Reproducibility was measured by unweighted kappa values and interpreted as follows: < 0.2, poor; 0.2–0.6, fair/moderate; > 0.6, substantial. Kappa values for the 12 lesions evaluated in 20 cases by the six pathologists were: acute chorioamnionitis/maternal inflammatory response (any, 0.93; severe 0.76; advanced stage, 0.49); chronic (subacute) chorioamnionitis (0.25); acute chorioamnionitis/fetal inflammatory response (any, 0.90; severe, 0.55; advanced stage, 0.52); chorionic vessel thrombi (0.37); peripheral funisitis (0.84); acute villitis (0.90); acute intervillositis/intervillous abscesses (0.65), and decidual plasma cells (0.30). Adoption of this clearly defined, clinically relevant, and pathologically reproducible terminology could enhance clinicopathologic correlation and provide a framework for future clinical research.

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OBJECTIVE: It has been suggested that women with scleroderma (systemic sclerosis, SSc) have cervical changes that may lead to obstetrical or postoperative complications. We evaluate histopathologic features characteristic of SSc in cervicovaginal tissue from women with SSc and compare them to age matched controls. METHODS: Records from the Scleroderma Registry at Wayne State University were matched with surgical specimens in the anatomic pathology files at Hutzel Hospital. Five women with SSc (2 with limited SSc, 3 with diffuse SSc; mean age 49 yrs) were identified who had cervical or vaginal tissue specimens available for evaluation. Small arterioles and surrounding connective tissue in these specimens and those from 26 age matched controls (15 normotensive, 11 hypertensive) were evaluated in blinded fashion. RESULTS: The following specific histopathological features were evaluated in the SSc patients: duplication or disruption of the internal elastica in 5 (100%), medial hypertrophy in 5 (100%), adventitial changes in 3 (60%), connective tissue fibrosis in 1 (20%), and vasculitis in 1 (20%). There was no significant difference in the frequency of the histopathologic changes between SSc and control patients when evaluated independently. However, the presence of 3 or more features was significantly more frequent in the SSc patients (100%) than in the controls (38%) (p = 0.018). CONCLUSION: The histopathological features evaluated were collectively more frequent in SSc patients; however, many of the control patients also exhibited similar abnormalities. In the female lower genital tract these changes, previously attributed solely to SSc, may be related to other factors.

Ring chromosomes are uncommon findings in prenatal diagnosis. Growth retardation is the most significant manifestation, in particular among patients with rings of larger chromosomes. A 30-year-old gravida 1, para 0 white woman was referred for genetic counseling because of maternal anxiety. Cytogenetic analysis of amniotic fluid cells at 16 weeks gestation revealed an abnormal mosaic female chromosome complement; 46,XX,r(11)(p15q25)[14]/45,XX,-11[7]. The ring 11 showed no detectable loss of chromosomal material at 450 band level. Both parents had a normal karyotype. Fluorescence in situ hybridization demonstrated intact subtelomeric regions in the ring chromosome. A targeted ultrasound evaluation at the time of consultation suggested no significant abnormalities. The parents were counseled and subsequently decided to terminate the pregnancy. The autopsy revealed an immature female fetus with abnormal craniofacial features including brachycephaly, low-set ears and hypertelorism, bicornuate uterus, and calcifications in the renal tubules. The abnormal phenotypes could be a consequence of the ring instability, submicroscopic deletion, and/or alteration of genetic material at the site of fusion. © 2001 Wiley-Liss, Inc.

AbstractFetal obstructive uropathy has seldom been described in trisomy syndromes, and its relationship to these syndromes remains unclear. Five trisomic male fetuses, four with trisomy 18 and one with trisomy 21, were identified out of 110 fetuses evaluated for fetal obstructive uropathy. We performed detailed examination on the urinary tracts of four of these fetuses, three with trisomy 18 and one with trisomy 21, following termination in the second trimester. All four had a markedly distended urinary bladder (megacystis), abdominal wall distension, and a small, poorly developed urethra thoughout its full length. All four also had poor development of the prostate with virtual absence of glandular development, as compared to age-matched controls. Posterior urethral valves were not identified in any case. Three of the fetuses (two with trisomy 18 and one with trisomy 21) had unilateral or bilateral hydroureters, and resulting renal tubulocystic or glomerulocystic change. Review of this database reveals an unexpectedly high frequency of trisomies, particularly trisomy 18, suggesting that the relationship may not be coincidental. Abnormal prostate development may be causally related to fetal obstructive uropathies and may be an under-recognized trait in trisomy syndromes. Karyotypic analysis of all fetuses with obstructive uropathy is important since in utero surgical intervention may be contraindicated in cases of fetal aneuploidy.Copyright © 2000 S. Karger AG, Basel

PROBLEM: Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with reduced fetal survival, recurrent abortions, and other pregnancy complications. Some of the autoantibodies found in SLE bind to laminins (LNs), which play an important role in the implantation of the fertilized ovum in humans.
 METHOD OF STUDY: To elucidate the role of these specific autoantibodies, chorionic villous explants from 6–7‐week‐old human placentas were established as organ cultures on laminin‐1 (LN‐1), collagen IV (CN‐IV) or uncoated culture dishes. The cultures were then exposed to a mouse monoclonal anti‐DNA/anti‐LN‐1 antibody, to human polyclonal lupus antibodies cross‐reacting with LN‐1, a function‐blocking polyclonal antibody to LN‐1, polyclonal antibodies to CN‐IV, or IgG control.
 RESULTS: The explants attached to LN‐1 and CN‐IV, but not to uncoated culture dishes. LN‐1 promoted migration of trophoblast, whereas CN‐IV promoted migration of fibroblast‐like cells. Trophoblast attachment and migration were abolished in a dose‐dependent manner by all three antibodies to LN‐1, but not by antibodies to CN‐IV or IgG control. Furthermore, the effect of anti‐LN antibodies was abolished by preincubating them with LN‐1.
 CONCLUSIONS: These studies suggest that anti‐DNA antibodies cross‐reacting with LNs may play a role in early pregnancy failure in SLE patients by interfering with placental implantation.

Traumatic lymphatic leaks are uncommon in children. Outcomes of conservative treatment are variable with surgery being often necessary. Lymphangiography has been successful in adults. Its utility in children is rarely reported. We report two cases of successful lymphangiographic treatment of traumatic lymphatic leak in children. First patient was a 15-year-old male developed a large right-sided pleural effusion 3 weeks after being physical assaulted. Tube thoracostomy yielded high volume chylous output. After failed conservative, operative and initial radiological interventions, he underwent bilateral femoral lymphangiography demonstrating abnormal ducts with contrast extravasation. This was controlled using coils and cyanoacrylate glue. Second patient was an 8-year-old male who following a road traffic accident underwent surgery for left diaphragmatic rupture. Drain was placed in the retroperitoneum where chylous fluid was observed. Postoperatively, after resuming diet, drains had significant chylous output. Lymphangiogram performed via inguinal nodes demonstrated abnormal right retroperitoneal nodes. The drain was exchanged for a pigtail catheter away from the lymphatics resulting in improved lymphatic flow. Lymphangiography is useful for treatment of traumatic lymphatic leaks in children. It should be considered early when conservative treatments fail. We present current evidence on lymphatic mapping and intervention for lymphatic leaks in children with a proposed algorithm.

Objective.Angiogenesis has been shown to correlate positively with the presence of metastatic disease in some tumors, but has not been studied in invasive vulvar squamous cell carcinoma. Fifty cases of invasive vulvar squamous cell carcinoma were studied in an effort to correlate angiogenesis with stage, survival, and pattern of invasion.Methods.These patients were diagnosed between 1987 and 1993. Microvessels were identified immunohistochemically using antibody to Factor VIII, and areas of greatest microvessel density associated with tumor were counted. The pattern of invasion was categorized as “spray,” “pushing,” or “mixed.” The mean microvessel count was correlated with surgical and clinical stage, pattern of invasion, and survival.Results.Mean microvessel counts in surgical stage I/II cases (31.1 ± 7.3) were not significantly different from stage III/IV cases (26.3 ± 8.6) (P= 0.089). Similarly mean microvessel counts in clinical stage I/II cases (31.6 ± 11.9) were not significantly different from stage III/IV cases (27.0 ± 8.7) (P= 0.198). Seventeen patients who died of disease had mean counts of 26.1 ± 6.4, while 21 patients alive with or without evidence of disease had counts of 31.1 ± 10.8 (P= 0.087). Mean microvessel counts did not vary significantly with the spray pattern (30.1 ± 8.7), pushing pattern (31.4 ± 12.9), or mixed pattern of invasion (31.4 ± 12.9) (P= 0.920).Conclusions.Tumor angiogenesis in vulvar squamous cell carcinoma does not correlate positively with stage, survival, or pattern of invasion and cannot be used as a prognostic indicator.

Ovarian leiomyomas are uncommon and have not been systematically studied. The clinical and histopathologic features of 15 ovarian leiomyomas were evaluated, including their clinical presentation, size, cellularity, mitotic index, presence of degeneration, and hyalinization. The mean age of women with ovarian leiomyomas was 45.8 years. The presenting sign was an adnexal mass in 7 (47), uterine leiomyomas in 4 (26), contralateral adnexal mass in 2 (13), and other signs in 2 (13) women. Thirteen leiomyomas had mitotic indices <1/10 high-power-fields (HPFs), including one cellular leiomyoma, and 2 had mitotic indices between 1 and 2/10 HPFs. The cellular leiomyoma and those with a mitotic index of ≥1/10 HPFs had an average size of 10 cm. The remaining leiomyomas with mitotic indices <1/10 HPFs had an average size of 3.4 cm. Two leiomyomas exhibited central degeneration, and hyaline change was present in 5 leiomyomas, 4 of which were at least 4 cm in size. The majority of ovarian leiomyomas (78) were associated with uterine leiomyomas; hyperplastic endometrial polyps were present in 2 cases. Follow-up (mean, 9.6 months) was available in 8 cases, and all had no evidence of recurrence. In conclusion, ovarian leiomyomas exhibit a spectrum of features that are similar to uterine leiomyomas. Although the prognosis is presumed to be good, the short follow-up period of this series precluded definitive evaluation of their natural history.

Smooth muscle differentiation in the ovary is rare, and its histopathologic spectrum, including ovarian smooth muscle metaplasia (SMM), has not been well described. The clinicopathologic findings in 48 ovaries with SMM from 40 women are reported. The average age of women with ovarian SMM was 55.6 years (range, 34 to 86 years). Foci of SMM were semiquantitatively characterized as 1+ in 46 (1 to 3 foci), 2+ in 37 (4 to 6 foci), and 3+ in 17 (>6 foci). SMM was bilateral in 8 (23) of the 35 patients who had bilateral oophorectomies. SMM was intimately associated with another ovarian process in 28 (58) cases, including ovarian cysts (11), endometriosis (3), granulosa cell tumors (3), extensive stromal luteinization (1), ovarian fibroma (1), adhesions (1), and folliculogenesis (8). Ovaries with 2+ to 3+ SMM were associated with another ovarian lesion significantly more often than those with 1+ SMM (p < 0.01). Most women with ovarian SMM (86) also had uterine leiomyomas. Significant endometrial pathology was present in 13 (37) of 35 simultaneously removed uteri. In conclusion, SMM occurs most often in perimenopausal or post-menopausal women, most of whom also have uterine leiomyomas. Ovarian SMM is usually confined to a few microscopic fields, is bilateral in <25 of patients, and is often associated with other ovarian lesions.

We report the clinicopathologic features of three women, 40 years of age or older, with malignant genital tract immature teratomas. All had FIGO stage III, grade II or grade III tumors. One tumor arose from the fallopian tube, the second from the ovary, and the third involved the cortical surfaces of both ovaries with minimal parenchymal involvement. The tumors weighed 1700, 5660, and 330 g and had histologic features similar to those generally seen in younger women. Two of the women died within 1 year of diagnosis. Interval growth of tumor after treatment with chemotherapy was documented in the third patient; she was reexplored and all of the excised tumor was composed of mature tissues. These cases affirm that, although rare, malignant germ cell tumors can occur in older peri- or postmenopausal women.

ABSTRACT: We describe extensive placental involvement by hepatoblastoma in a 2600 g, 33-week estimated gestational age (EGA) hydropic female fetus with the hepatoblastoma otherwise limited to the liver. The placenta weighed 1190 g and histopathologic examination revealed diffuse tumor emboli in chorionic villous vessels. The placental tumor exhibited a cytologic appearance similar to the primary tumor and showed strong alpha-fetoprotein staining. Although unusual, other congenital tumors, including neuroblastoma and leukemia, have also been described metastatic to the placenta. This case emphasizes the important role of careful histopathologic examination of the placenta which, combined with immunohistochemistry and clinicopathologic correlation, may establish a diagnosis and possibly obviate the need for invasive neonatal diagnostic procedures.

ABSTRACT: Choriocarcinoma arising in the placenta, or intraplacental choriocarcinoma, has seldom been reported, particularly in the absence of maternal metastases. Reluctance to diagnose choriocarcinoma in the presence of chorionic villi can delay diagnosis; however, timely diagnosis of choriocarcinoma is prognostically important, both for the mother and infant. We report the clinicopathologic findings in five mothers and infants in whom choriocarcinoma was identified in the placenta. None of the mothers had a history of gestational trophoblastic disease in previous pregnancies. Three placentas were similar with a single small lesion grossly suggesting a small infarct; microscopically these consisted of infarcted areas surrounded by choriocarcinoma. These three mothers were unusual in that none had metastatic choriocarcinoma; two were treated with chemotherapy and remained disease-free; the third was lost to follow-up shortly following delivery. The remaining two mothers had known pulmonary metastases at time of delivery. One of these latter two placentas contained a large marginal lesion microscopically identified as choriocarcinoma. The fifth placenta had rare microscopic foci of choriocarcinoma, and sheets of necrotic choriocarcinoma were identified in “blood clot” submitted with the placenta. In four of the five cases the choriocarcinoma appeared to be arising from otherwise normal chorionic villi, and in no case was there invasion of the villous stroma. All of the infants survived, and none had evidence of choriocarcinoma. These cases support the concept that choriocarcinoma associated with otherwise normal pregnancy arises in the placenta and may be more common than reported.

We report on 32 cases of Candidafunisitis and describe the associated clinicopathologic features. The Candidafunisitis was characterized grossly by small, circumscribed, yellow-white nodules on the umbilical cord surface and, microscopically, by subamnionic microabscesses in which fungal organisms were demonstrable. Chorioamnionitis was present in all cases. Twenty-four (75%) of the 32 infants were premature. There were 7 perinatal deaths, all in immature fetuses. Five (16%) of the 32 fetuses had congenital candidiasis. Five (16%) of the mothers had a history of intrauterine foreign body, including intrauterine contraceptive device in three and cervical cerclage in two. The diagnosis of Candidafunisitis should prompt a careful examination for fetal infection, even though it is associated with congenital candidiasis in only a minority of the cases.