Breast Cancer-Related Lymphedema Results in Impaired Epidermal Differentiation and Tight Junction Dysfunction.

Breast cancer-related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of FLG and the tight junction protein ZO-1 in skin affected by moderate lymphedema or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to those in the controls (areas without backflow and from the unaffected arm). In vitro stimulation of keratinocytes with lymph fluid obtained from patients undergoing lymphedema surgery led to the same changes as well as increased expression of keratin 14, a marker of immature keratinocytes. Finally, using mouse models of lymphedema, we showed that similar to the clinical scenario, the expression of skin barrier proteins was decreased relative to that in normal skin and that colonization with Staphylococcus epidermidis bacteria amplified this effect as well as lymphedema severity. Taken together, our findings suggest that lymphatic fluid stasis contributes to skin barrier dysfunction in lymphedema.

Ultrasound shear wave elastography in pediatric stricturing small bowel Crohn disease: correlation with histology and second harmonic imaging microscopy.

BACKGROUND: Preclinical animal as well as small exploratory ex vivo and in vivo human studies have suggested that bowel wall shear wave speed (SWS) measurements may be a noninvasive biomarker of intestinal damage. OBJECTIVE: To evaluate the relationships between bowel wall stiffness, measured using ultrasound shear wave elastography (SWE), and intestinal fibrosis and smooth muscle hypertrophy as determined by (1) histology and (2) second harmonic imaging microscopy (SHIM) in surgically resected ileal strictures from pediatric Crohn disease patients. MATERIALS AND METHODS: Nineteen pediatric Crohn disease patients with symptomatic ileal strictures underwent research ultrasound examinations before surgical resection between December 2017 and September 2020. Two-dimensional SWE was performed through the area of the most severe stenosis, with measurements obtained from the bowel wall at the 9:00, 12:00 and 3:00 o'clock locations with 0%, 10% and 20% abdominal strain. Overall right lower quadrant stiffness also was documented. Median bowel wall and overall right lower quadrant SWS measurements were correlated with bowel wall histological scores of inflammation, fibrosis and smooth muscle proliferation as well as SHIM collagen signal. RESULTS: Diagnostic ultrasound SWE imaging was obtained from 18 participants. The median age was 16.8 years. There were negative correlations between histological mucosal active inflammation and both bowel wall SWS with 10% abdominal strain (r=-0.50, P = 0.04) and overall right lower quadrant SWS with 20% abdominal strain (r=-0.69, P = 0.002). There were positive correlations between histological muscularis propria inner layer smooth muscle hypertrophy and both median bowel wall SWS with 10% abdominal strain (r = 0.72, P = 0.002) and overall right lower quadrant SWS with 20% abdominal strain (r = 0.71, P = 0.002). There were no associations between ultrasound stiffness metrics and bowel wall SHIM collagen measurements. CONCLUSION: Bowel wall and overall right lower quadrant ultrasound stiffness measurements correlate with mucosal active inflammation and muscularis propria smooth muscle hypertrophy in pediatric stricturing ileal Crohn disease, but not with intestinal fibrosis.

US Backscatter for Liver Fat Quantification: An AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

Nonalcoholic fatty liver disease (NAFLD) is believed to affect one-third of American adults. Noninvasive methods that enable detection and monitoring of NAFLD have the potential for great public health benefits. Because of its low cost, portability, and noninvasiveness, US is an attractive alternative to both biopsy and MRI in the assessment of liver steatosis. NAFLD is qualitatively associated with enhanced B-mode US echogenicity, but visual measures of B-mode echogenicity are negatively affected by interobserver variability. Alternatively, quantitative backscatter parameters, including the hepatorenal index and backscatter coefficient, are being investigated with the goal of improving US-based characterization of NAFLD. The American Institute of Ultrasound in Medicine and Radiological Society of North America Quantitative Imaging Biomarkers Alliance are working to standardize US acquisition protocols and data analysis methods to improve the diagnostic performance of the backscatter coefficient in liver fat assessment. This review article explains the science and clinical evidence underlying backscatter for liver fat assessment. Recommendations for data collection are discussed, with the aim of minimizing potential confounding effects associated with technical and biologic variables.

Intestinal adenocarcinoma originating from an undiagnosed Meckel's diverticulum.

Meckel's diverticulum is a congenital anomaly leading to the formation of a true diverticulum in the distal small intestine. Though most are asymptomatic and discovered incidentally, Meckel's diverticuli can give rise to a wide range of symptoms. Rarely, this can be a malignancy, most commonly a carcinoid tumor. Other cancers have also been reported, with adenocarcinomas being particularly rare. Here, we report the case of a 62-year-old man presenting to the emergency room with vague gastrointestinal symptoms. Subsequent workup revealed a 3 cm mass in the distal jejunum/proximal ileum, which was located within a previously undiagnosed Meckel's diverticulum. The mass was sent to pathology, who confirmed an adenocarcinoma arising from a small bowel diverticulum. This case serves as an important reminder of the malignant potential of a Meckel's diverticulum and adds to the ongoing discussion regarding whether prophylactic diverticulectomy should be recommended to patients with a known Meckel's diverticulum.

Suppression of p53 response by targeting p53-Mediator binding with a stapled peptide.

DNA-binding transcription factors (TFs) remain challenging to target with molecular probes. Many TFs function in part through interaction with Mediator, a 26-subunit complex that controls RNA polymerase II activity genome-wide. We sought to block p53 function by disrupting the p53-Mediator interaction. Through rational design and activity-based screening, we characterize a stapled peptide, with functional mimics of both p53 activation domains, that blocks p53-Mediator binding and selectively inhibits p53-dependent transcription in human cells; importantly, this "bivalent" peptide has negligible impact, genome-wide, on non-p53 target genes. Our proof-of-concept strategy circumvents the TF entirely and targets the TF-Mediator interface instead, with desired functional outcomes (i.e., selective inhibition of p53 activation). Furthermore, these results demonstrate that TF activation domains represent viable starting points for Mediator-targeting molecular probes, as an alternative to large compound libraries. Different TFs bind Mediator through different subunits, suggesting this strategy could be broadly applied to selectively alter gene expression programs.

Transcription factor enrichment analysis (TFEA) quantifies the activity of multiple transcription factors from a single experiment.

Detecting changes in the activity of a transcription factor (TF) in response to a perturbation provides insights into the underlying cellular process. Transcription Factor Enrichment Analysis (TFEA) is a robust and reliable computational method that detects positional motif enrichment associated with changes in transcription observed in response to a perturbation. TFEA detects positional motif enrichment within a list of ranked regions of interest (ROIs), typically sites of RNA polymerase initiation inferred from regulatory data such as nascent transcription. Therefore, we also introduce muMerge, a statistically principled method of generating a consensus list of ROIs from multiple replicates and conditions. TFEA is broadly applicable to data that informs on transcriptional regulation including nascent transcription (eg. PRO-Seq), CAGE, histone ChIP-Seq, and accessibility data (e.g., ATAC-Seq). TFEA not only identifies the key regulators responding to a perturbation, but also temporally unravels regulatory networks with time series data. Consequently, TFEA serves as a hypothesis-generating tool that provides an easy, rigorous, and cost-effective means to broadly assess TF activity yielding new biological insights.

Chemotherapy-associated neutropenic enterocolitis of the transverse colon post right hemicolectomy.

Neutropenic enterocolitis (NE) is a life-threatening infection of the immunocompromised. NE ubiquitously affects the cecum, often with involvement of the ascending colon and ileum. Classically, NE is associated with high mortality leading to the frequent use of aggressive treatment strategies including surgery. Although conservative approaches are often successful, there are currently no standardized treatment guidelines for NE and it is unclear when such strategies should be implemented. Here, we describe a patient with suspected chemotherapy-associated NE despite having previously undergone a right hemicolectomy. As computed tomography imaging failed to provide a conclusive diagnosis, we performed a gentle endoscopic evaluation that affirmed a diagnosis of NE of the transverse colon, and suggested the patient would benefit from conservative treatment. This case demonstrates that endoscopy can be a safe and useful tool in the diagnosis of NE, and is an important reminder that NE can affect any part of the gastrointestinal tract.

Transcriptional Responses to IFN-γ Require Mediator Kinase-Dependent Pause Release and Mechanistically Distinct CDK8 and CDK19 Functions.

Transcriptional responses to external stimuli remain poorly understood. Using global nuclear run-on followed by sequencing (GRO-seq) and precision nuclear run-on sequencing (PRO-seq), we show that CDK8 kinase activity promotes RNA polymerase II pause release in response to interferon-γ (IFN-γ), a universal cytokine involved in immunity and tumor surveillance. The Mediator kinase module contains CDK8 or CDK19, which are presumed to be functionally redundant. We implemented cortistatin A, chemical genetics, transcriptomics, and other methods to decouple their function while assessing enzymatic versus structural roles. Unexpectedly, CDK8 and CDK19 regulated different gene sets via distinct mechanisms. CDK8-dependent regulation required its kinase activity, whereas CDK19 governed IFN-γ responses through its scaffolding function (i.e., it was kinase independent). Accordingly, CDK8, not CDK19, phosphorylates the STAT1 transcription factor (TF) during IFN-γ stimulation, and CDK8 kinase inhibition blocked activation of JAK-STAT pathway TFs. Cytokines such as IFN-γ rapidly mobilize TFs to "reprogram" cellular transcription; our results implicate CDK8 and CDK19 as essential for this transcriptional reprogramming.

Ileal carcinoid tumor represents after prolonged remission as a solitary breast mass.

While the metastatic spread of breast cancer is well documented, the breast is seldom a site for metastasis. Non-mammillary cancers can involve the breast or axilla, though this is exceedingly rare with few reported instances. Here, we present the case of a 62-year-old woman who attended an outpatient breast clinic with a history of an ileal carcinoid tumor complicated by multi-organ metastasis. Her disease was in clinical remission for several years, though she recently re-presented with a single solitary lesion to the breast that was later confirmed as a recurrence of her carcinoid tumor. This serves as an important reminder that the breast can indeed be a site for metastasis. As metastatic breast lesions can often be difficult to diagnose, it is essential to obtain a thorough medical history in order to determine the appropriate clinical course.

Repeat presentation of large rectal foreign body requiring surgical intervention.

Irretrievable rectal foreign bodies can cause significant distress and generally require emergency medical attention. While smaller objects can often be removed trans-anally, larger objects typically require more invasive intervention. Here, we report the case of a 57-year-old man who had previously presented to the emergency department with a baseball lodged in the rectosigmoid that required a laparotomy. One year later, he represented with a significantly larger object also affixed in the rectosigmoid. Exploratory laparotomy revealed an edematous, inflamed bowel with extensive adhesions from the pervious surgery. Given the degree of tissue damage and large size of the object, the decision was made to perform a Hartmann's procedure. The object, an 11 × 10 cm rubber chew toy, was successfully removed and the patient was referred to the appropriate mental health professionals during follow-up.

Non-implant associated primary cutaneous anaplastic large cell lymphoma of the breast.

Anaplastic large cell lymphomas (ALCL) comprise a group of rare, related T-cell neoplasms that typically present on the extremities. Infrequently, cutaneous ALCL can involve the breast, where it is near ubiquitously associated with breast implants. Here, we present the rare case of a 70-year-old woman with primary cutaneous ALCL of the breast with no history of breast augmentation. This serves as an important reminder that in some instances, breast ALCL can be idiopathic. Further, given the potential for malignancy, any changes to the breast skin should be diagnosed quickly in order to ensure rapid delivery of the appropriate treatment.

Ultrasound Elastography to Assess Botulinum Toxin A Treatment for Post-stroke Spasticity: A Feasibility Study.

The aim of the study was to evaluate the feasibility of using ultrasound elastography to assess the effect of botulinum toxin A (BoNT-A) treatment on post-stroke spasticity of the upper limb. In this prospective study, we performed ultrasound elastography (strain imaging and acoustic radiation force impulse-based shear wave elastography) of the spastic biceps brachii muscle in seven patients (five men and two women, mean age: 45y) who underwent BoNT-A injection treatment for post-stroke spasticity of the upper limb. We measured ultrasound elasticity parameters including axial strain ratio (SR) (SR = muscle strain/reference strain), longitudinal SR and shear wave velocity of the biceps muscle immediately before and 17-30 d (mean: 22 d) after BoNT-A injection. Statistical analyses included a two-tailed paired t-test to examine the difference in ultrasound elasticity parameters of bilateral biceps muscles before and after BoNT-A treatment and a Spearman rank correlation coefficient (rs) to analyze the correlation of ultrasound elasticity parameters to clinical assessment with the Modified Ashworth Scale (MAS) and Tardieu Scale (TS). The difference in ultrasound elasticity parameters before and after BoNT-A treatment was significant (p < 0.05) in the treated spastic muscle. The correlation of ultrasound elasticity parameters with MAS and the angle of catch and range of motion in TS were also significant (rs = 0.55-0.95, p < 0.05). Our results suggest that ultrasound elastography is feasible in assessment of the effectiveness of BoNT-A treatment for post-stroke spasticity of the upper limb.

Massive adult cystic lymphangioma of the breast.

Adult cystic lymphangiomas are exceedingly rare tumors resulting from malformation of the lymphatic vessels. Like their pediatric counterparts, these lesions almost exclusively involve the head and neck. However, adult cystic lymphangiomas have been reported in several organs. Those involving the breast are exceptionally rare, with only a few reported instances. Here, we present the case of a 27-year-old woman who attended a surgical breast clinic with a 2-year history of a large, disfiguring left breast mass. Pathology was consistent with adult cystic lymphangioma of the breast. Measuring 21.0 × 20.0 × 6.0 cm3, this represents the second largest of its kind and the largest reported case in an African American patient.

Transvaginal Ultrasound Shear Wave Elastography for the Evaluation of Benign Uterine Pathologies: A Prospective Pilot Study.

OBJECTIVES: This study evaluated the diagnostic performance of transvaginal ultrasound (TVUS) shear wave elastography (SWE) for evaluating uterine adenomyosis and leiomyomas. METHODS: Institutional Review Board approval was obtained for prospective enrollment of 34 premenopausal women with pelvic pain and/or bleeding between January 2015 and June 2016. TVUS SWE was performed with regions of interest in multiple uterine segments and shear wave velocities(SWVs) were recorded. Reference pelvic magnetic resonance examinations were performed and reviewed without access to the ultrasound results. RESULTS: Continuous variables were analyzed using means, t tests, and analysis of variance. Magnetic resonance imaging revealed adenomyosis in 6 women (12 uterine segments) and leiomyomas in 12 women (28 segments). On a per-patient basis, mean SWV in 16 women with no adenomyosis or leiomyoma was 4.3 ± 1.7 m/s, compared with 5.7 ± 2.3 m/s in 18 women with a magnetic resonance diagnosis of myometrial pathology (P < .0002; 95% confidence interval, -2.2, -0.6). On a per-segment basis, SWV in normal myometrium was 4.8 ± 1.9 m/s, compared with 4.9 ± 2.5 m/s in adenomyosis and 5.6 ± 2.5 m/s in leiomyoma (P = .34 by one-way analysis of variance). In pairwise comparison, SWV for adenomyosis and leiomyoma did not differ significantly (P = .40). CONCLUSIONS: TVUS SWE did not distinguish adenomyosis from leiomyoma. However, our pilot study demonstrated that myometrial SWVs were higher in uteri with adenomyosis and leiomyomas than in uteri with myometrium with no abnormalities suggesting a potential role for SWE in treatment response assessment.

Quantitative Assessment of Liver Stiffness Using Ultrasound Shear Wave Elastography in Patients With Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Study.

OBJECTIVES: The purpose of this study was to compare hepatic stiffness on ultrasound (US) shear wave elastography (SWE) in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation versus patients with no underlying liver disease. METHODS: We performed a retrospective analysis of 4901 patients who underwent abdominal US examinations with adjunctive liver SWE between August 2014 and December 2016. Each patient was scanned supine with gentle breath holding on LOGIQ E9 (GE Healthcare, Waukesha, WI) or Epiq (Philips Healthcare, Andover, MA) US machines (3-6 MHz). Three to 10 measurements were made intercostally in the right hepatic lobe, following manufacturers' guidelines before release of the 2015 Society of Radiologists in Ultrasound consensus or the 2015 Society of Radiologists in Ultrasound consensus. The median and standard deviation of the shear wave velocity (SWV) were obtained. A 2-sample t test with the Welch approximation was used for statistical analysis. RESULTS: Six patients had documented hepatic chronic GVHD or a high clinical suspicion of liver chronic GVHD. All had normal pretransplant liver function test results and no pretransplant or posttransplant hepatic infection. The control group, obtained from the same database, contained 10 patients with normal liver function test results, no abdominal pain, and no history of liver disease or conditions that may have caused liver stiffness changes. The SWVs in patients with chronic GVHD were double those in the control group (1.96 ± 0.28 versus 0.98 ± 0.27 m/s; P < .0001). CONCLUSIONS: Patients with chronic GVHD had substantially higher hepatic parenchymal SWVs than patients without liver disease, indicating increased tissue stiffness. To our knowledge, this phenomenon has not been previously reported in chronic GVHD and suggests potential utility of SWE for diagnosis and monitoring of disease progression and the treatment response in this cohort of patients.

Mathematical modeling of energy consumption in the acute inflammatory response.

When a pathogen invades the body, an acute inflammatory response is activated to eliminate the intruder. In some patients, runaway activation of the immune system may lead to collateral tissue damage and, in the extreme, organ failure and death. Experimental studies have found an association between severe infections and depletion in levels of adenosine triphosphate (ATP), increase in nitric oxide production, and accumulation of lactate, suggesting that tissue energetics is compromised. In this work we present a differential equations model that incorporates the dynamics of ATP, nitric oxide, and lactate accompanying an acute inflammatory response and employ this model to explore their roles in shaping this response. The bifurcation diagram of the model system with respect to the pathogen growth rate reveals three equilibrium states characterizing the health, aseptic and septic conditions. We explore the domains of attraction of these states to inform the instantiation of heterogeneous virtual patient populations utilized in a survival analysis. We then apply the model to study alterations in the inflammatory response and survival outcomes in metabolically altered conditions such as hypoglycemia, hyperglycemia, and hypoxia.

TGFß Blockade Augments PD-1 Inhibition to Promote T-Cell-Mediated Regression of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains remarkably lethal with a 5-year survival rate of 8%. This is mainly attributed to the late stage of presentation, as well as widespread resistance to conventional therapy. In addition, PDAC tumors are largely nonimmunogenic, and most patients have displayed incomplete responses to cancer immunotherapies. Our group has previously identified TGFß as a crucial repressor of antitumor immune function in PDAC, particularly with respect to cytotoxic T lymphocytes. However, pharmacologic inhibition of TGFß signaling has had limited efficacy in clinical trials, failing to promote a significant antitumor immune response. Hence, in this work, we extend our analysis to identify and circumvent the mechanisms of resistance to TGFß signal inhibition in PDAC. Consistent with our previous observations, adoptive transfer of TGFß-insensitive CD8+ T cells led to the near complete regression of neoplastic disease in vivo However, we demonstrate that this cannot be recapitulated via global reduction in TGFß signaling, through either genetic ablation or pharmacologic inhibition of TGFBR1. In fact, tumors with TGFß signal inhibition displayed increased PD-L1 expression and had no observable change in antitumor immunity. Using genetic models of advanced PDAC, we then determined that concomitant inhibition of both TGFß and PD-L1 receptors led to a reduction in the neoplastic phenotype, improving survival and reducing disease-associated morbidity in vivo Combined, these data strongly suggest that TGFß and PD-L1 pathway inhibitors may synergize in PDAC, and this approach warrants clinical consideration.

Can Contrast-Enhanced Sonography Detect Bowel Wall Fibrosis in Mixed Inflammatory and Fibrotic Crohn Disease Lesions in an Animal Model?

OBJECTIVES: To determine whether contrast-enhanced sonographic quantitative perfusion parameters can detect bowel wall fibrosis in the setting of mixed inflammatory and fibrotic lesions in a Crohn disease animal model. METHODS: This study was approved by the institutional Committee on the Use and Care of Animals. Multiple (range, 1-5) 2,4,6-trinitrobenzenesulfonic acid-ethanol enemas were used to create intestinal inflammatory lesions with variable fibrosis in female Lewis rats. Low-mechanical index contrast-enhanced sonography was performed 3 days after the final enema using a 0.2-mL bolus of sulfur hexafluoride microbubbles injected through a tail vein. Contrast-enhanced sonographic data were analyzed with software that converts video data into echo-power (linearized) data. Colorectal lesions were scored for histopathologic inflammation and fibrosis; bowel wall collagen was quantified by Western blotting. The Spearman correlation was used to assess associations between contrast-enhanced sonographic quantitative parameters and bowel wall collagen; the Kruskal-Wallis test was used to compare continuous results between histopathologic groups. RESULTS: Thirty-one animals were included in our analysis. Animals were placed into 3 histopathologic cohorts: (1) severe bowel wall inflammation/minimal or no fibrosis (n = 11); (2) severe bowel wall inflammation/moderate fibrosis (n = 9); and (3) severe bowel wall inflammation/severe fibrosis (n = 11). Western blotting showed a significant difference in bowel wall collagen between histopathologic cohorts (P = .0001). There was no correlation between any contrast-enhanced sonographic quantitative parameter and bowel wall collagen (P > .05). There was no difference between histopathologic cohorts for any contrast-enhanced sonographic quantitative parameter (P > .05). CONCLUSIONS: Contrast-enhanced sonographic quantitative perfusion parameters failed to effectively detect bowel wall fibrosis in the setting of superimposed inflammation in a Crohn disease animal model.

Clinical Effectiveness of Prospectively Reported Sonographic Twinkling Artifact for the Diagnosis of Renal Calculus in Patients Without Known Urolithiasis.

OBJECTIVE: The purpose of this study was to determine the clinical effectiveness of prospectively reported sonographic twinkling artifact for the diagnosis of renal calculus in patients without known urolithiasis. MATERIALS AND METHODS: All ultrasound reports finalized in one health system from June 15, 2011, to June 14, 2014, that contained the words "twinkle" or "twinkling" in reference to suspected renal calculus were identified. Patients with known urolithiasis or lack of a suitable reference standard (unenhanced abdominal CT with ≤ 2.5-mm slice thickness performed ≤ 30 days after ultrasound) were excluded. The sensitivity, specificity, and positive likelihood ratio of sonographic twinkling artifact for the diagnosis of renal calculus were calculated by renal unit and stratified by two additional diagnostic features for calcification (echogenic focus, posterior acoustic shadowing). RESULTS: Eighty-five patients formed the study population. Isolated sonographic twinkling artifact had sensitivity of 0.78 (82/105), specificity of 0.40 (26/65), and a positive likelihood ratio of 1.30 for the diagnosis of renal calculus. Specificity and positive likelihood ratio improved and sensitivity declined when the following additional diagnostic features were present: sonographic twinkling artifact and echogenic focus (sensitivity, 0.61 [64/105]; specificity, 0.65 [42/65]; positive likelihood ratio, 1.72); sonographic twinkling artifact and posterior acoustic shadowing (sensitivity, 0.31 [33/105]; specificity, 0.95 [62/65]; positive likelihood ratio, 6.81); all three features (sensitivity, 0.31 [33/105]; specificity, 0.95 [62/65]; positive likelihood ratio, 6.81). CONCLUSION: Isolated sonographic twinkling artifact has a high false-positive rate (60%) for the diagnosis of renal calculus in patients without known urolithiasis.

Modeling and Hemofiltration Treatment of Acute Inflammation.

The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin) and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D) differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL)-6, tumor necrosis factor (TNF), and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC) algorithm was synthesized to control a hemoadsorption (HA) device, a blood purification treatment for acute inflammation. A particle filter (PF) algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i) the apparent primary mechanism of HA efficacy is white blood cell (WBC) capture, with cytokine capture a secondary benefit; and (ii) differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.