Surgical Site Infections in Trauma Exploratory Laparotomies Preoperative Ceftriaxone and Metronidazole Versus Cefoxitin.

Surgical site infections (SSIs) remain a significant cause of morbidity and mortality in patients undergoing traumatic exploratory laparotomy. The goal of this study was to compare antibiotic usage and subsequent outcomes in patients undergoing traumatic exploratory laparotomy. A retrospective chart analysis and a chi-square test of independence were performed to examine the relation between preoperative cefoxitin versus ceftriaxone and metronidazole and the rate of SSI development. 323 patients were analyzed, 111 patients receiving cefoxitin and 212 patients receiving ceftriaxone and metronidazole. The proportion of patients who developed SSI was 16.2% for the cefoxitin group and 9.9% for the ceftriaxone and metronidazole group, X2 (1, N = 323) = 2.7, P = .098, thus displaying no statistical difference in the development of SSIs between patients in the cefoxitin group when compared to the ceftriaxone and metronidazole group.

Microcystic lymphatic malformations in Turner syndrome are due to somatic mosaicism of PIK3CA.

Turner syndrome (45,X) is caused by a complete or partial absence of a single X chromosome. Vascular malformations occur due to abnormal development of blood and/or lymphatic vessels. They arise from either somatic or germline pathogenic variants in the genes regulating growth and apoptosis of vascular channels. Aortic abnormalities are a common, known vascular anomaly of Turner syndrome. However, previous studies have described other vascular malformations as a rare feature of Turner syndrome and suggested that vascular abnormalities in individuals with Turner syndrome may be more generalized. In this study, we describe two individuals with co-occurrence of Turner syndrome and vascular malformations with a lymphatic component. In these individuals, genetic testing of the lesional tissue revealed a somatic pathogenic variant in PIK3CA-a known and common cause of lymphatic malformations. Based on this finding, we conclude that the vascular malformations presented here and likely those previously in the literature are not a rare part of the clinical spectrum of Turner syndrome, but rather a separate clinical entity that may or may not co-occur in individuals with Turner syndrome.

Fetal Heart Rate < 3rd Percentile for Gestational Age Can Be a Marker of Inherited Arrhythmia Syndromes.

BACKGROUND: Repeated fetal heart rates (FHR) < 3rd percentile for gestational age (GA) with 1:1 atrioventricular conduction (sinus bradycardia) can be a marker for long QT syndrome. We hypothesized that other inherited arrhythmia syndromes might present with fetal sinus bradycardia. METHODS: We reviewed pregnancies referred with sinus bradycardia to the Colorado Fetal Care Center between 2013 and 2023. FHR/GA data, family history, medication exposure, normalized isovolumic contraction times (n-IVRT), postnatal genetic testing, and ECGs at 4-6 weeks after birth were reviewed. RESULTS: Twenty-nine bradycardic subjects were evaluated by fetal echocardiography. Five were lost to follow-up, one refused genetic testing, and one had negative genetic testing for any inherited arrhythmia. Six had non-genetic causes of fetal bradycardia with normal prenatal n-IVRT and postnatal QTc. Thirteen carried pathogenic variants in RYR2 (n = 2), HCN4 (n = 2), KCNQ1 (6), and other LQTS genes (n = 4). The postnatal QTc was <470 ms in subjects with RYR2, HCN4, and two of those with KCNQ1 mutations, and >470 ms in subjects with CALM 2, KCNH2, SCN5A, and four of those with KCNQ1 mutations. LQTS and RYR2 mutations were associated with prolonged n-IVRT, but HCN4 was not. Two fetuses died in utero with variants of uncertain significance (CACNA1 and KCNE1). Cascade testing uncovered six affected but undiagnosed parents and confirmed familial inheritance in five. CONCLUSION: In addition to heralding LQTS, repeated FHR < 3rd percentile for GA is a risk factor for other inherited arrhythmia syndromes. These findings suggest that genetic testing should be offered to infants with a history of FHR < 3rd percentile for GA even if the postnatal ECG demonstrates a normal QTc interval.

Genomic profiling informs diagnoses and treatment in vascular anomalies.

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.

Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.

Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2­dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.

Widespread keratinocytic epidermal nevus with an associated chylous pericardial effusion.

A 17-year-old male presented for review of a widespread keratinocytic epidermal nevus (KEN) in the setting of a chronic pericardial effusion. Biopsy of the epidermal nevus revealed a KRAS mutation. Pericardiocentesis revealed a chylous effusion and magnetic resonance lymphangiogram demonstrated an underlying lymphatic malformation. There are rare case reports of KEN with an associated KRAS mutation. This case highlights the importance of being alert to epidermal nevus syndrome, particularly in patients with a widespread nevus and seemingly unrelated pathology.

Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly.

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

Multicompartment Dynamic Contrast Magnetic Resonance Lymphangiography in Diagnosis of Complicated Lymphatic Anomaly.

Background: To describe the dynamic contrast magnetic resonance lymphangiography (DCMRL) findings of three patients with complicated lymphatic anomaly (CLA) and protein losing enteropathy. We further discuss the importance of a multicompartment (intrahepatic [IH], intramesenteric [IM], and intranodal [IN]) DCMRL in delineating central lymphatic flow pathologies. Methods and Results: This is a retrospective study of three patients-one adult and two children who individually underwent the three-compartment DCMRL, namely IN-DCMRL, IH-DCMRL, and IM-DCMCRL. Findings from the results of the DCMRL for these three patients were obtained from the medical records and compared. Using the multicompartment imaging modalities, chylous fluid leakage into the peritoneum was observed using IM-DCMRL and IH-DCMRL but not IN-DCMRL for one of the patients in the case series. In contrast, leakage of chyle into the mediastinum was noted using IN-DCMRL but not IH-DCMRL and IM-DCMRL on another patient in this case series. Conclusion: Owing to the variability in outlining lymphatic flow pathologies, multicompartment imaging gives a more global picture of individual conduction disorders, has the potential to improve clinical assessment, and in some cases leads to a diagnosis of the abnormality and thus provides a better understanding of lymphatic flow anomalies in patients with CLAs.

Refining the stress gradient hypothesis for mixed species groups of African mammals.

Species interactions such as facilitation and predation influence food webs, yet it is unclear how they are mediated by environmental gradients. Here we test the stress gradient hypothesis which predicts that positive species interactions increase with stress. Drawing upon spatially-explicit data of large mammals in an African savanna, we tested how predation risk and primary productivity mediate the occurrence of mixed species groups. Controlling for habitat structure, predation risk by lions and primary productivity affected the frequency of mixed species groups in species-specific ways, likely reflecting distinct stress perceptions. To test whether mixed species groups indicate positive interactions, we conducted network analyses for specific scenarios. Under predation risk, dyadic associations with giraffes were more pronounced and metrics of animal networks changed markedly. However, dyadic association and network metrics were weakly mediated by primary productivity. The composition of mixed species groups was associated with similarities in prey susceptibility but not with similarities in feeding habits of herbivores. Especially predation risk favoured the frequency of mixed species groups and pronounced dyadic associations which dilute predation risk and increase predator detection. While our results provide support for the stress gradient hypothesis, they also highlight that the relative importance of stressors is context-dependent.

How we approach lymphedema in the pediatric population.

Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities.

How we approach lymphedema in the pediatric population.

Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities.

Risk perception and tolerance shape variation in agricultural use for a transboundary elephant population.

To conserve wide-ranging species in human-modified landscapes, it is essential to understand how animals selectively use or avoid cultivated areas. Use of agriculture leads to human-wildlife conflict, but evidence suggests that individuals may differ in their tendency to be involved in conflict. This is particularly relevant to wild elephant populations. We analysed GPS data of 66 free-ranging elephants in the Serengeti-Mara ecosystem to quantify their use of agriculture. We then examined factors influencing the level of agricultural use, individual change in use across years and differences in activity budgets associated with use. Using clustering methods, our data grouped into four agricultural use tactics: rare (<0.6% time in agriculture; 26% of population), sporadic (0.6%-3.8%; 34%), seasonal (3.9%-12.8%; 31%) and habitual (>12.8%; 9%). Sporadic and seasonal individuals represented two-thirds (67%) of recorded GPS fixes in agriculture, compared to 32% from habitual individuals. Increased agricultural use was associated with higher daily distance travelled and larger home range size, but not with age or sex. Individual tactic change was prevalent and the habitual tactic was maintained in consecutive years by only five elephants. Across tactics, individuals switched from diurnal to nocturnal activity during agricultural use, interpreted as representing similar risk perception of cultivated areas. Conversely, tactic choice appeared to be associated with differences in risk tolerance between individuals. Together, our results suggest that elephants are balancing the costs and benefits of crop usage at both fine (e.g. crop raid events) and long (e.g. yearly tactic change) temporal scales. The high proportion of sporadic and seasonal tactics also highlights the importance of mitigation strategies that address conflict arising from many animals, rather than targeted management of habitual crop raiders. Our approach can be applied to other species and systems to characterize individual variation in human resource use and inform mitigations for human-wildlife coexistence.

Misdiagnosis of capillary malformations in darker skin phototypes.

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations.

Persistence and photochemical transformation of water soluble constituents from industrial crude oil and natural seep oil in seawater.

The persistence and transformation of water soluble chemical constituents derived from surface oil from the 2015 Refugio Oil Spill and from a nearby natural seep were evaluated under simulated sunlight conditions. Photoirradiation resulted in enhanced oil slick dissolution, which was more pronounced in spill oil compared to seep oil. Nontargeted analysis based on GC × GC/TOF-MS revealed that photoirradiation promoted oil slick dissolution, and more water soluble compounds were released from spill oil (500 compounds) than from seep oil (180 compounds), most of them (488 in spill oil and 150 in seep oil) still persisting in solution after 67 days of photoirradiation. First-order degradation rate coefficients of humic-like water soluble constituents were found to be 0.26 day-1 and 0.29 day-1 for irradiated spill and seep samples, respectively. The decreases in humic-like fluorescence, specific UV absorbance, and aromatic compounds without corresponding decreases in DOC concentration support indirect photochemical transformation in addition to complete photomineralization.

Severe Lymphatic Disorder Resolved With MEK Inhibition in a Patient With Noonan Syndrome and SOS1 Mutation.

Noonan syndrome is a multiorgan system disorder mediated by genetic defects along the RASknown as RASopathies. It is the second most common syndromic cause of congenital heart disease and, in ∼20% of the cases, is associated with severe lymphatic disorders, including chylothorax and protein-losing enteropathy. Recently, we reported on the use of mitogen-activated protein kinase inhibition in a patient with an ARAF mutation and severe lymphatic disorder leading to an abrupt improvement in symptoms and complete remodeling of the central lymphatic system. Here, we present a patient with Noonan syndrome and severe lymphatic abnormality, leading to transfusion-dependent upper gastrointestinal bleeding and protein-losing enteropathy. The patient stopped responding to medical therapy and underwent several lymphatic interventional procedures, which led only to a temporary improvement in symptoms. Because of a lack of other treatment options, an expanded access approval was obtained, and the patient initiated treatment by mitogen-activated protein kinase inhibition using trametinib. This led to resolution of her symptoms, with complete normalization of her electrolyte levels, hemoglobin, and albumin within 3 months of starting the drug. Similar to the previously reported case, she also had complete and generalized remodeling of her lymphatic system. In patients with RAS pathway defects complicated by a severe lymphatic disorder, inhibition of the RAS-MAPK pathway should be considered as a possible treatment option in patients who failed conventional treatment and might be a first-line treatment in the future.

Racial/Ethnic Minority Children With Cancer Experience Higher Mortality on Admission to the ICU in the United States.

OBJECTIVE: We investigated whether differences in survival exist between children of various racial/ethnic groups with cancer admitted to the PICU. DESIGN: A retrospective multicenter analysis was conducted using Virtual Pediatric Systems data from reporting centers. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were analyzed using mixed-effects logistic regression modeling to assess for differences in mortality. SETTING: One hundred thirty-five PICUs in the United States. PATIENTS: Pediatric patients with cancer admitted to PICUs in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study details the analysis of 23,128 PICU admissions of 12,232 unique oncology patients representing 3% of all PICU admissions with 1,610 deaths (7.0% case fatality). African American (8.5%) and Hispanic children (8.1%) had significantly higher mortality (p < 0.05) compared with Caucasian children (6.3%). Regional analysis showed Hispanic patients to have higher mortality in the West in the United States, whereas African American patients in the South in the United States had higher mortality. A pulmonary disease diagnosis in Hispanics increased odds of mortality (odds ratio, 1.39; 95% CI, 1.13-1.70), whereas a diagnosis of shock/sepsis increased risk for mortality in African Americans (odds ratio, 1.56; 95% CI, 1.11-2.20) compared with Caucasians. There were no differences between races/ethnic groups in the rates of limitations of care. After controlling for Pediatric Risk of Mortality III, PICU length of stay, stem cell transplant status, readmissions, cancer type (solid, brain, hematologic), mechanical ventilation days, and sex, Hispanic (odds ratio, 1.24; 95% CI, 1.05-1.47) and African Americans (odds ratio, 1.37; 95% CI, 1.14-1.66) had significantly higher odds of mortality compared with Caucasians. CONCLUSIONS: The results show that after controlling for severity and cancer type, a child's race, ethnicity, and region of presentation influence mortality in the PICU. This suggests that additional investigation is warranted along with a need to rethink our approach to the evaluation and treatment of critically ill African American and Hispanic children with cancer.

Rethinking assessment of success of mitigation strategies for elephant-induced crop damage.

Crop damage is the most common impact of negative interactions between people and elephants and poses a significant threat to rural livelihoods and conservation efforts. Numerous approaches to mitigate and prevent crop damage have been implemented throughout Africa and Asia. Despite the documented high efficacy of many approaches, losses remain common, and in many areas, damage is intensifying. We examined the literature on effectiveness of crop-damage-mitigation strategies and identified key gaps in evaluations. We determined there is a need to better understand existing solutions within affected communities and to extend evaluations of effectiveness beyond measurement of efficacy to include rates of and barriers to adoption. We devised a conceptual framework for evaluating effectiveness that incorporates the need for increased emphasis on adoption and can be used to inform the design of future crop-damage mitigation assessments for elephants and conflict species more widely. The ability to prevent crop loss in practice is affected by both the efficacy of a given approach and rates of uptake among target users. We identified the primary factors that influence uptake as local attitudes, sustainability, and scalability and examined each of these factors in detail. We argue that even moderately efficacious interventions may make significant progress in preventing damage if widely employed and recommend that wherever possible scientists and practitioners engage with communities to build on and strengthen existing solutions and expertise. When new approaches are required, they should align with local attitudes and fit within limitations on labor, financial requirements, and technical capacity.

Replanteamiento de la Evaluación del Éxito de las Estrategias de Mitigación del Daño a Cultivos Causado por Elefantes Resumen El daño a los cultivos es el impacto más común generado por las interacciones negativas entre las personas y los elefantes. Actualmente representa una amenaza significativa para el sustento rural y los esfuerzos de conservación. Se han implementado numerosas estrategias para mitigar y prevenir el daño a los cultivos en toda África y Asia. A pesar de la documentación de la eficiencia de las estrategias, las pérdidas todavía son comunes y, en muchas áreas, el daño se está intensificando. Examinamos la literatura sobre la efectividad de las estrategias de mitigación del daño a cultivos e identificamos vacíos importantes en su evaluación. Determinamos que existe una necesidad por entender de mejor manera las soluciones existentes en las comunidades afectadas y por extender las evaluaciones de eficiencia más allá de las medidas de eficacia para que incluyan las tasas y barreras de la adopción. Diseñamos un marco de trabajo conceptual para la evaluación de la eficiencia, el cual incorpora la necesidad de un incremento en el énfasis de la adopción y puede usarse para informar a los diseñadores de las futuras evaluaciones de la mitigación de daños a cultivos causados por elefantes u otras especies conflictivas de manera más amplia. La capacidad de poder prevenir la pérdida de cultivos en práctica está afectada tanto por la eficiencia de una estrategia dada como por las tasas de aceptación entre los usuarios diana. Identificamos como los factores primarios que influyen sobre la aceptación a las actitudes locales, la sustentabilidad y la adaptabilidad, y examinamos cada uno de estos factores a detalle. Argumentamos que incluso las intervenciones moderadamente eficientes pueden llevar a cabo un progreso significativo en la prevención del daño si se emplean ampliamente. También recomendamos que, en donde sea posible, los científicos y los practicantes de la conservación participen con las comunidades para construir y fortalecer las soluciones y el conocimiento existentes. Cuando se requieran nuevas estrategias, éstas deberán alinearse con las actitudes locales y deberán encajar dentro de las limitaciones de la labor, los requisitos financieros y la capacidad técnica.

Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?

BACKGROUND: The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity. Based on the genetic defects in PIDs, novel gene/pathway-targeted therapies have been evaluated, which could be relevant in the atopic syndrome as well. Therefore, we aimed to define subclasses within the atopic syndrome based on the expression profiles of immune cell lineages of healthy mice. METHODS: Overlap between known atopy-related genes as described in the Human Gene Mutation Database and disease-causing genes of monogenic PIDs was evaluated. Clusters of atopy-related genes were based on the overlap in their co-expressed genes using the gene expression profiles of immune cell lineages of healthy mice from the Immunological Genome Project. We analyzed pathways involved in the atopic syndrome using Ingenuity Pathway Analysis. RESULTS: Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and PID-related genes (n = 278). We identified seven distinct clusters of atopy-related genes. Functional pathway analysis of all atopy-related genes showed relevance of T helper cell-mediated pathways. CONCLUSIONS: This study shows a model to define clusters within the atopic syndrome based on gene expression profiles of immune cell lineages. Our results support the hypothesis that both genetic mechanisms and immune dysregulation play a role in the pathogenesis. It also opens up the possibility for novel therapeutic targets and a more tailored approach towards personalized medicine.