A multicenter study of DDAVP versus platelet transfusions for antiplatelet agent reversal in patients with traumatic brain injury.

BACKGROUND: Antiplatelet agents have been shown to worsen outcomes following traumatic injury. Research on desmopressin (DDAVP) and platelet transfusion for antiplatelet reversal is limited. We aimed to evaluate the effect of these agents on patients taking pre-injury antiplatelet medications who experienced traumatic brain injury (TBI) after blunt trauma. METHODS: This is a retrospective cohort study of adult trauma patients from 2014 to 2021 on aspirin and/or a P2Y12 inhibitor. Patients were stratified into groups based on if they received DDAVP, platelets, both agents, or neither. RESULTS: Of 5525 included patients, 4696 (85.4%) were not reversed, 461 (8.4%) received platelets, 173 (3.1%) received DDAVP, and 172 (3.1%) received both reversals. There was no statistically significant difference in length of stay between, but patients who received platelets or both reversals were more likely to have hospital complications (p < 0.05), longer hospital length of stay (p < 0.001), and longer ICU length of stay (p < 0.001) compared to those who did not receive reversal. A subgroup analysis of patients with a head AIS of 4 or 5 confirmed these findings. CONCLUSIONS: Patients who received platelets or both reversals had a longer length of hospital stay and length of ICU stay. It is difficult to recommend one treatment over another based on our results alone. Further studies are needed to help clarify the risks and benefits of reversal agents in this patient population.

Postoperative Oral Rehydration and Regimented Follow-up Decrease Readmissions After Colorectal Surgery That Includes Ileostomies.

BACKGROUND: Ileostomies constitute 15% to 43% of readmissions after colorectal surgery, often due to dehydration and acute kidney injury. Prior institutional interventions decreased readmissions but not among patients who underwent new ileostomies. OBJECTIVE: To evaluate readmissions among patients who underwent new ileostomies after postoperative oral rehydration solution and standardized clinic visits. DESIGN: Retrospective analysis of prospective database. SETTINGS: Enhanced recovery colorectal surgery service. PATIENTS: Patients who underwent new ileostomy before and after intervention. INTERVENTIONS: Postoperative oral rehydration solution and postdischarge clinic visits with review of inputs/outputs, antimotility and appliance needs, and trained nurse reeducation 4 to 7 days after discharge, 30 days postoperatively, and every 1 to 2 weeks thereafter as needed. MAIN OUTCOME MEASURES: Readmission rate due to dehydration/acute kidney injury (primary), emergency department visits, and readmission rates overall and for specific diagnoses. Analysis used univariate and weighted techniques. RESULTS: A total of 312 patients (199 preintervention; 113 postintervention) were included, with a mean age of 59.0 years. Patients were predominantly White (94.9%) and evenly split between men and women. The most common diagnosis was diverticulitis (43.3%). The most common procedure was high anterior resection (38.8%), followed by low anterior resection (16.35%). Patient and procedure characteristics were well matched between groups. Multivariate analysis demonstrated that readmission rate due to dehydration/acute kidney injury significantly decreased between pre- and postintervention study groups (45.7% vs 16.5%, p = 0.039). Emergency department visits due to dehydration/acute kidney injury (12.0% vs 1.7%, p < 0.001) and readmissions from all causes (24.33% vs 10.6%, p = 0.005) also significantly decreased. Other complications were not significantly different between groups. Average stoma output 24 hours before (776 vs 625 mL, p = 0.005) and after (993 vs 890 mL, p = 0.025) discharge was significantly decreased in the postintervention group. LIMITATIONS: Retrospective single-center study. CONCLUSIONS: An oral rehydration solution and frequent standardized postdischarge visits led by trained nursing staff decreased readmissions and emergency department visits among patients who underwent new ileostomies after colorectal surgery. See Video Abstract . LA REHIDRATACIN ORAL POSOPERATORIA Y EL SEGUIMIENTO REGLAMENTADO REDUCEN LOS REINGRESOS EN PACIENTES DE CIRUGA COLORRECTAL CON ILEOSTOMAS: ANTECEDENTES:Las ileostomías constituyen del 15 al 43% de los reingresos después de la cirugía colorrectal, a menudo debido a la deshidratación y la lesión renal aguda. Las intervenciones institucionales previas redujeron los reingresos, pero no entre los pacientes con nuevas ileostomías.OBJETIVO:Evaluar los reingresos entre pacientes con nuevas ileostomías después del uso de solución de rehidratación oral postoperatoria y visitas clínicas estandarizadas.DISEÑO:Análisis retrospectivo de base de datos prospectiva.AJUSTES:Servicio de cirugía colorrectal de recuperación mejorada.PACIENTES:Pacientes con ileostomía nueva antes y después de la intervención.INTERVENCIÓN(ES):Solución de rehidratación oral posoperatoria y visitas clínicas posteriores al alta con revisión de entradas/salidas, antimotilidad y necesidades de aparatos, y reeducación de enfermeras capacitadas 4-7 días después del alta, 30 días después de la operación y cada 1-2 semanas después, según sea necesario.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de readmisión debido a deshidratación/lesión renal aguda (primaria), tasa de urgencias y de readmisión en general y para diagnósticos específicos. El análisis utilizó técnicas univariadas y ponderadas.RESULTADOS:Se incluyeron un total de 312 pacientes (199 preintervención; 113 postintervención), con una edad media de 59,0 años. Los pacientes eran predominantemente blancos (94,9%) y se dividieron equitativamente entre hombres y mujeres. El diagnóstico más frecuente fue diverticulitis (43,3%). El procedimiento más común fue la resección anterior alta (38,8 %) seguida de la resección anterior baja (16,35 %). Las características del paciente y del procedimiento coincidieron bien entre los grupos. El análisis multivariante demostró que la tasa de reingreso debido a deshidratación/lesión renal aguda disminuyó significativamente entre los grupos de estudio antes y después de la intervención (45,7 % frente a 16,5 %, p = 0,039). Las visitas a urgencias por deshidratación/insuficiencia renal aguda (12,0 % frente a 1,7 %, p < 0,001) y los reingresos por todas las causas (24,33 % frente a 10,6 %, p = 0,005) también disminuyeron significativamente. Otras complicaciones no fueron significativamente diferentes entre los grupos. El gasto medio del estoma 24 horas antes (776 ml frente a 625 ml, p = 0,005) y después (993 ml frente a 890 ml, p = 0,025) del alta disminuyó significativamente en el grupo posterior a la intervención.LIMITACIONES:Estudio retrospectivo de centro único.CONCLUSIONES:Una solución de rehidratación oral y frecuentes visitas estandarizadas posteriores al alta dirigidas por personal de enfermería capacitado redujeron los reingresos y las visitas al servicio de urgencias entre los pacientes con nuevas ileostomías después de la cirugía colorrectal. ( Traducción-Dr. Yolanda Colorado ).

Alvimopan is associated with favorable outcomes in open and minimally invasive colorectal surgery: a regional database analysis.

BACKGROUND: Alvimopan is a µ-opioid receptor antagonist associated with shorter time to gastrointestinal recovery in patients having open colorectal surgery. Data demonstrating the benefit of perioperative alvimopan for the minimally invasive surgical approach are inconsistent. The aim of this study is to determine colorectal surgery groups that benefit from perioperative alvimopan. METHODS: This is a retrospective cohort analysis of colorectal surgery patients who had, and patients who did not have, perioperative alvimopan in the Michigan Surgical Quality Collaborative regional risk-adjusted database from 2018 through 2021. Main outcome measures were postoperative length of hospital stay, time to return of bowel function, and postoperative ileus. RESULTS: There were 10,010 patients (30.3% open, 40.5% laparoscopic, 12.7% hand-assist laparoscopic, 43.5% robotic) who met inclusion criteria-4919 received alvimopan in the perioperative period and 5091 did not. When compared to those not receiving alvimopan, unadjusted outcomes showed that the alvimopan group had significantly shorter postoperative length of stay (4.75 days vs 5.5 days, p < 0.001), shorter time to return of bowel function (1.61 days vs 2.01 days, p < 0.001) and less postoperative ileus (5.45% vs 7.94%, p < 0.001). After adjustment, regression models confirmed that alvimopan was associated with an 9.6% reduction in hospital length of stay (p < 0.001), a 14.9% shorter time to return of bowel function (p < 0.001), and a 42.1% reduction in postoperative ileus (p < 0.001). Subgroup analysis showed significant benefit of alvimopan for all three outcomes in patients having the minimally invasive approach. CONCLUSIONS: Alvimopan is associated with shorter hospital length of stay, shorter time to return of bowel function, and decreased postoperative ileus when administered to patients undergoing colorectal surgery. Benefit is not limited to the open approach and includes minimally invasive laparoscopic and robotic colorectal procedures.

The Effect of Antiplatelet Agents on Thromboelastography.

BACKGROUND: Thomboelastography (TEG) is a point of care viscoelastic test that provides an assessment of clot formation and kinetics. Antiplatelet agents are commonly used but there is limited literature evaluating their possible effects on overall clot kinetics. We aimed to evaluate the relationship between antiplatelet agents and clot kinetics as defined by TEG. METHODS: This is a retrospective study of adult patients who underwent TEG from February 2018 to July 2020. Patients who received anticoagulants or blood transfusions within 72 hours, had an incomplete TEG, were diagnosed with COVID-19, or had liver failure were excluded. Patients were stratified based on antiplatelet status. RESULTS: Of 1060 patients, 119 were included (50 controls, 69 antiplatelet agents-37 aspirin monotherapy, 26 dual antiplatelet therapy). Between the control and antiplatelet therapy groups, there was no significant difference in clot time, maximal clot strength, or fibrinogen level. When compared to control patients, patients on dual antiplatelets had significantly higher fibrinogen levels (408.1 mg/dL vs 481.5 mg/dL, P = .013) but no significant differences in clot time or maximal clot strength. In our subgroup analysis, patients on dual antiplatelets had increased maximal clot strength (58.8° vs 63°, P = .005) and fibrinogen levels (384.1 mg/dL vs 481.5 mg/dL, P = .005) compared to those on aspirin alone. DISCUSSION: Compared to control patients and those on aspirin alone, patients on dual antiplatelets have increased maximal clot strength and increased fibrinogen levels. These results can help physicians better target product resuscitation in patients who are on antiplatelet agents.

Myocardial infarction after craniotomy for asymptomatic meningioma.

A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient's recent neurosurgery, standard post-MI care was contraindicated and he was instead managed symptomatically in the intensive care unit. Echocardiogram on postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3.

Acute Colonic Pseudo-Obstruction.

CASE SUMMARY: A 33-year-old man with a history of chronic alcohol use, generalized anxiety disorder, and hypertension presented to the emergency department after a syncopal event. He was admitted to the medical intensive care unit for alcohol withdrawal, requiring intubation and sedation. On hospital day 7, abdominal x-ray image demonstrated a dilated cecum to 12 cm, transverse colon dilation to 7 cm, and decompressed distal colon ( Fig. 1 ). CT scan of the abdomen and pelvis confirmed dilation of the cecum and ascending and transverse colons ( Fig. 2 ). Colonoscopy showed no evidence of distal obstruction, but colonic distension persisted, and he subsequently underwent cecal decompression with an open "blow-hole" cecostomy fully matured at skin level via a small right lower quadrant incision. The nasogastric tube was removed on postoperative day 2, and his diet was slowly advanced. Abdominal x-ray image on postoperative day 5 demonstrated no colonic dilation. He was discharged home on postoperative day 7. The patient re-presented to the hospital 3 months later with cecostomy prolapse. He underwent cecostomy takedown with ileocecectomy via circumstomal incision. He was discharged home on postoperative day 2.

Evaluation of four methods to identify the homozygotic sex chromosome in small populations.

BACKGROUND: Whole genomes are commonly assembled into a collection of scaffolds and often lack annotations of autosomes, sex chromosomes, and organelle genomes (i.e., mitochondrial and chloroplast). As these chromosome types differ in effective population size and can have highly disparate evolutionary histories, it is imperative to take this information into account when analysing genomic variation. Here we assessed the accuracy of four methods for identifying the homogametic sex chromosome in a small population using two whole genome sequences (WGS) and 133 RAD sequences of white-tailed eagles (Haliaeetus albicilla): i) difference in read depth per scaffold in a male and a female, ii) heterozygosity per scaffold in a male and a female, iii) mapping to the reference genome of a related species (chicken) with annotated sex chromosomes, and iv) analysis of SNP-loadings from a principal components analysis (PCA), based on the low-depth RADseq data. RESULTS: The best performing approach was the reference mapping (method iii), which identified 98.12% of the expected homogametic sex chromosome (Z). Read depth per scaffold (method i) identified 86.41% of the homogametic sex chromosome with few false positives. SNP-loading scores (method iv) identified 78.6% of the Z-chromosome and had a false positive discovery rate of more than 10%. Heterozygosity per scaffold (method ii) did not provide clear results due to a lack of diversity in both the Z and autosomal chromosomes, and potential interference from the heterogametic sex chromosome (W). The evaluation of these methods also revealed 10 Mb of putative PAR and gametologous regions. CONCLUSION: Identification of the homogametic sex chromosome in a small population is best accomplished by reference mapping or examining differences in read depth between sexes.

Towards reproducible metabarcoding data: Lessons from an international cross-laboratory experiment.

Advances in high-throughput sequencing (HTS) are revolutionizing monitoring in marine environments by enabling rapid, accurate and holistic detection of species within complex biological samples. Research institutions worldwide increasingly employ HTS methods for biodiversity assessments. However, variance in laboratory procedures, analytical workflows and bioinformatic pipelines impede the transferability and comparability of results across research groups. An international experiment was conducted to assess the consistency of metabarcoding results derived from identical samples and primer sets using varying laboratory procedures. Homogenized biofouling samples collected from four coastal locations (Australia, Canada, New Zealand and the USA) were distributed to 12 independent laboratories. Participants were asked to follow one of two HTS library preparation workflows. While DNA extraction, primers and bioinformatic analyses were purposefully standardized to allow comparison, many other technical variables were allowed to vary among laboratories (amplification protocols, type of instrument used, etc.). Despite substantial variation observed in raw results, the primary signal in the data was consistent, with the samples grouping strongly by geographical origin for all data sets. Simple post hoc data clean-up by removing low-quality samples gave the best improvement in sample classification for nuclear 18S rRNA gene data, with an overall 92.81% correct group attribution. For mitochondrial COI gene data, the best classification result (95.58%) was achieved after correction for contamination errors. The identified critical methodological factors that introduced the greatest variability (preservation buffer, sample defrosting, template concentration, DNA polymerase, PCR enhancer) should be of great assistance in standardizing future biodiversity studies using metabarcoding.

RAD sequencing of common whelk, Buccinum undatum, reveals fine-scale population structuring in Europe and cryptic speciation within the North Atlantic.

Buccinum undatum is a subtidal gastropod that exhibits clear spatial variation in several phenotypic shell traits (color, shape, and thickness) across its North Atlantic distribution. Studies of spatial phenotypic variation exist for the species; however, population genetic studies have thus far relied on a limited set of mitochondrial and microsatellite markers. Here, we greatly expand on previous work by characterizing population genetic structure in B. undatum across the North Atlantic from SNP variation obtained by RAD sequencing. There was a high degree of genetic differentiation between Canadian and European populations (Iceland, Faroe Islands, and England) consistent with the divergence of populations in allopatry (F ST > 0.57 for all pairwise comparisons). In addition, B. undatum populations within Iceland, the Faroe Islands, and England are typified by weak but significant genetic structuring following an isolation-by-distance model. Finally, we established a significant correlation between genetic structuring in Iceland and two phenotypic traits: shell shape and color frequency. The works detailed here enhance our understanding of genetic structuring in B. undatum and establish the species as an intriguing model for future genome-wide association studies.

Rare case of rectosigmoid stricture causing transverse colon volvulus.

A 60-year-old woman with remote history of sleeve gastrectomy presented with altered mental status after an unwitnessed fall. She was found to be hypothermic with lactic acidaemia, leucocytosis, positive urinalysis, and dilated ascending and transverse colon on cross-sectional imaging, initially thought to be secondary to faecal loading. She was admitted to the medical intensive care unit for resuscitation and broad-spectrum antibiotics for presumed urinary sepsis. She became acutely altered and underwent urgent flexible sigmoidoscopy by gastroenterology to evaluate for ischaemic colitis. During the procedure, there was concern for iatrogenic colon injury given the friability of the colonic mucosa, so the patient was taken urgently for exploratory laparotomy. Intraoperatively, she was found to have a transverse colon volvulus with large areas of patchy, gangrenous bowel without evidence of gross perforation. A rectosigmoid stricture with associated serosal tear, but no full-thickness injury was identified. An extended left hemicolectomy and end transverse colostomy was performed resulting in improvement in the patient's clinical status and eventual discharge to subacute rehab.

Biotic signals associated with benthic impacts of salmon farms from eDNA metabarcoding of sediments.

Environmental DNA (eDNA) metabarcoding can rapidly characterize the composition and diversity of benthic communities, thus it has high potential utility for routine assessments of benthic impacts of marine finfish farming. In this study, 126 sediment grab samples from 42 stations were collected at six salmon farms in British Columbia, Canada. Benthic community changes were assessed by both eDNA metabarcoding of metazoans and macrofaunal polychaete surveys. The latter was done by analysing 11,466 individuals using a combination of morphology-based taxonomy and DNA barcoding. Study objectives were to: (i) compare biotic signals associated with benthic impacts of salmon farming in the two data sources, and (ii) identify potential eDNA indicators to facilitate monitoring in Canada. Alpha diversity parameters were consistently reduced near fish cage edge and negatively correlated with pore-water sulphide concentration, with coefficients ranging from -0.62 to -0.48. Although Polychaeta are a common indicator group, the negative correlation with pore-water sulphide concentration was much stronger for Nematoda OTU richness (correlation coefficient: -0.86) than for Polychaeta (correlation coefficient: -0.38). Presence/absence of Capitella generally agreed well between the two methods despite that they differed in the volume of sediments sampled and the molecular marker used. Multiple approaches were used to identify OTUs related to organic enrichment statuses. We demonstrate that eDNA metabarcoding generates biotic signals that could be leveraged for environmental assessment of benthic impacts of fish farms in multiple ways: both alpha diversity and Nematoda OTU richness could be used to assess the spatial extent of impact, and OTUs related to organic enrichment could be used to develop local biotic indices.

Computed Tomography for Acute Appendicitis Diagnosis and Confirmation in Men : Trends and Cost Implications.

INTRODUCTION: The classic findings of acute appendicitis-right lower quadrant pain, anorexia, and leukocytosis-have been well known. However, emergency medicine and surgical providers continue to rely on imaging to confirm the diagnosis. We aimed to evaluate the increase in reliance on computed tomography (CT) scans for acute appendicitis diagnosis over time. METHODS: We conducted a retrospective study of patients ≥18 years presenting to UNC Hospitals with signs and symptoms of acute appendicitis who subsequently underwent appendectomy from 2011 to 2015. Demographic, clinical, laboratory, and pathologic data were reviewed. We evaluated the incidence of CT scans stratified by year, age, and sex. RESULTS: Within our male population, 55.2% (278/504) had classic appendicitis symptoms. Of the 278 male patients with classic appendicitis symptoms, 248 underwent CT imaging. Male patients <45 years of age were more likely to present with classic appendicitis symptoms (216/357, 60.5%) compared with patients aged 46-65 (52/108, 48.1%) or >65 (10/39, 25.6%). Of the male patients <45 years with classic appendicitis symptoms, the incidence of CT scans increased over time (68.3% in 2011, 84.2% in 2012, 92.3% in 2013, 93.9% in 2014, 92.3% in 2015). When considering the 216 CT scans that could have been avoided in our population, we calculate an approximate savings of $173 998.80 over 5 years. CONCLUSION: The incidence of CT scans for acute appendicitis confirmation has increased over time even in men. CT scans for the diagnosis or confirmation of acute appendicitis should rarely be indicated in men aged <45 years with classic appendicitis symptoms.

Regulation of Na/K-ATPase expression by cholesterol: isoform specificity and the molecular mechanism.

We have reported that the reduction in plasma membrane cholesterol could decrease cellular Na/K-ATPase α1-expression through a Src-dependent pathway. However, it is unclear whether cholesterol could regulate other Na/K-ATPase α-isoforms and the molecular mechanisms of this regulation are not fully understood. Here we used cells expressing different Na/K-ATPase α isoforms and found that membrane cholesterol reduction by U18666A decreased expression of the α1-isoform but not the α2- or α3-isoform. Imaging analyses showed the cellular redistribution of α1 and α3 but not α2. Moreover, U18666A led to redistribution of α1 to late endosomes/lysosomes, while the proteasome inhibitor blocked α1-reduction by U18666A. These results suggest that the regulation of the Na/K-ATPase α-subunit by cholesterol is isoform specific and α1 is unique in this regulation through the endocytosis-proteasome pathway. Mechanistically, loss-of-Src binding mutation of A425P in α1 lost its capacity for regulation by cholesterol. Meanwhile, gain-of-Src binding mutations in α2 partially restored the regulation. Furthermore, through studies in caveolin-1 knockdown cells, as well as subcellular distribution studies in cell lines with different α-isoforms, we found that Na/K-ATPase, Src, and caveolin-1 worked together for the cholesterol regulation. Taken together, these new findings reveal that the putative Src-binding domain and the intact Na/K-ATPase/Src/caveolin-1 complex are indispensable for the isoform-specific regulation of Na/K-ATPase by cholesterol.

Epithelial and Endothelial Adhesion of Immune Cells Is Enhanced by Cardiotonic Steroid Signaling Through Na+/K+-ATPase-α-1.

Background Recent studies have highlighted a critical role for a group of natriuretic hormones, cardiotonic steroid (CTS), in mediating renal inflammation and fibrosis associated with volume expanded settings, such as chronic kidney disease. Immune cell adhesion is a critical step in the inflammatory response; however, little is currently understood about the potential regulatory role of CTS signaling in this setting. Herein, we tested the hypothesis that CTS signaling through Na+/K+-ATPase α-1 (NKA α-1) enhances immune cell recruitment and adhesion to renal epithelium that ultimately advance renal inflammation. Methods and Results We demonstrate that knockdown of the α-1 isoform of Na/K-ATPase causes a reduction in CTS-induced macrophage infiltration in renal tissue as well reduces the accumulation of immune cells in the peritoneal cavity in vivo. Next, using functional adhesion assay, we demonstrate that CTS-induced increases in the adhesion of macrophages to renal epithelial cells were significantly diminished after reduction of NKA α-1 in either macrophages or renal epithelial cells as well after inhibition of NKA α-1-Src signaling cascade with a specific peptide inhibitor, pNaKtide in vitro. Finally, CTS-induced expression of adhesion markers in both endothelial and immune cells was significantly inhibited in an NKA α-1-Src signaling dependent manner in vitro. Conclusions These findings suggest that CTS potentiates immune cell migration and adhesion to renal epithelium through an NKA α-1-dependent mechanism; our new findings suggest that pharmacological inhibition of this feed-forward loop may be useful in the treatment of renal inflammation associated with renal disease.

A new approach to molecular biosurveillance of invasive species using DNA metabarcoding.

Non-indigenous species (NIS) reach every corner of the world, at times wreaking havoc on ecosystems and costing the global economy billions of dollars. A rapid and accurate biosurveillance tool tailored to a particular biogeographic region is needed to detect NIS when they are first introduced into an area as traditional detection methods are expensive and require specialized expertise. Metabarcoding of environmental and community DNA meets those biosurveillance requirements; a novel tool tailored to the Northwest Pacific Ocean is presented here using an approach that could revolutionize early detection of NIS. Eight newly designed genetic markers for multiple gene regions were implemented to meet the stringent taxonomic requirements for the detection of NIS across four major marine phyla. The tool was considered highly successful because it identified 12 known NIS in the study area and a further seven species representing potential new records. Overall community composition detected here was statistically different between substrate types; zooplankton sampling accounted for significantly higher species richness than filtered sea water in most cases, but this was dominated by mollusk and arthropod species. Both substrate types sampled were required to identify the wide taxonomic breadth of known NIS in the study area. Intensive sampling is known to be paramount for the detection of rare species, including new incursions of NIS, thus it is recommended to include diverse DNA sampling protocols based on species' life-history characteristics for broad detection capacity. Application of a metabarcoding-based molecular biosurveillance tool optimized for biogeographic regions enables rapid and accurate early detection across a wide taxonomic range to allow quick implementation of eradication or control efforts and potentially mitigate some of the devastating effects of NIS worldwide.

Risk of Perforation in the Era of Nonemergent Management for Acute Appendicitis.

Prompt appendectomy has long been the standard of care for acute appendicitis because of the risk of progression to perforation. Recently, studies have suggested nonemergent management of acute appendicitis. Our study aimed to determine changes in risk of rupture and complications in patients with appendicitis, with increasing time from symptom onset to treatment. Retrospective study of patients aged ≥18 years presenting to the University of North Carolina Hospitals with signs and symptoms of acute appendicitis who subsequently underwent appendectomy from 2011 to 2015 was performed. Demographic, clinical, laboratory, and pathologic data were reviewed. Bivariate analysis was performed to assess variables associated with increased risk of perforation. Poisson regression modeling was completed to evaluate the risk of perforation and postoperative abscess based on time from symptoms to treatment. Within our database of 1007 patients, the mean time from onset of symptoms to operative intervention was 3.24 ± 2.2 days. Modified Poisson regression modeling demonstrated the relative risk for perforation increases by 9% (RR 1.09, P < 0.001) for each day delay. Age (RR 1.03), male gender (RR 1.50), temperature on admission (RR 1.32), and the presence of fecalith (RR 1.89) statistically significantly increased the risk of perforation. Furthermore, for each day delay, there is an 8% increased risk of postoperative abscess (RR 1.08, P = 0.027). The relative risk for appendiceal perforation is 9 per cent per day delay with a resultant 8 per cent increased risk of postoperative abscess. Thus, appendectomy for acute appendicitis should remain an emergent procedure, given that delays in operative management lead to complications and increases in cost of care.

Appendiceal Malignancy: The Hidden Risks of Nonoperative Management for Acute Appendicitis.

One potential harm of nonoperative management for acute appendicitis is missed appendiceal cancer, a rare and often aggressive malignancy due to the frequency of late stage of diagnosis. Previous studies have reported an increasing incidence of appendiceal neoplasms in the population. This is a retrospective case-control study of 1007 adult patients, who presented to the University of North Carolina-Memorial Hospital (UNC-MH) between 2011 and 2015 with clinical signs and symptoms of appendicitis. We evaluated the incidence of primary appendiceal cancer in this population and determined factors that predict appendiceal cancer diagnosis using multivariate logistic regression analysis. The overall incidence of appendiceal neoplasm for adult patients presenting to UNC-MH with appendicitis from 2011 to 2015 was 2.3 per cent (23/1007). The incidence in patients without appendiceal perforation on pathology was 1.9 per cent (16/832). Age (odds ratio (OR) 1.03), number of days of abdominal pain (OR 1.16), self-reported fever (OR 2.08), appendiceal width (OR 1.95), and appendiceal wall thickness (OR 1.30) were predictors of appendiceal neoplasm diagnosis in patients that present with acute appendicitis. We recommend that an operative approach to acute appendicitis should remain the standard of care because operative management may not only be diagnostic but potentially therapeutic.

Telocinobufagin, a Novel Cardiotonic Steroid, Promotes Renal Fibrosis via Na⁺/K⁺-ATPase Profibrotic Signaling Pathways.

Cardiotonic steroids (CTS) are Na⁺/K⁺-ATPase (NKA) ligands that are elevated in volume-expanded states and associated with cardiac and renal dysfunction in both clinical and experimental settings. We test the hypothesis that the CTS telocinobufagin (TCB) promotes renal dysfunction in a process involving signaling through the NKA α-1 in the following studies. First, we infuse TCB (4 weeks at 0.1 µg/g/day) or a vehicle into mice expressing wild-type (WT) NKA α-1, as well as mice with a genetic reduction (~40%) of NKA α-1 (NKA α-1+/-). Continuous TCB infusion results in increased proteinuria and cystatin C in WT mice which are significantly attenuated in NKA α-1+/- mice (all p < 0.05), despite similar increases in blood pressure. In a series of in vitro experiments, 24-h treatment of HK2 renal proximal tubular cells with TCB results in significant dose-dependent increases in both Collagens 1 and 3 mRNA (2-fold increases at 10 nM, 5-fold increases at 100 nM, p < 0.05). Similar effects are seen in primary human renal mesangial cells. TCB treatment (100 nM) of SYF fibroblasts reconstituted with cSrc results in a 1.5-fold increase in Collagens 1 and 3 mRNA (p < 0.05), as well as increases in both Transforming Growth factor beta (TGFb, 1.5 fold, p < 0.05) and Connective Tissue Growth Factor (CTGF, 2 fold, p < 0.05), while these effects are absent in SYF cells without Src kinase. In a patient study of subjects with chronic kidney disease, TCB is elevated compared to healthy volunteers. These studies suggest that the pro-fibrotic effects of TCB in the kidney are mediated though the NKA-Src kinase signaling pathway and may have relevance to volume-overloaded conditions, such as chronic kidney disease where TCB is elevated.