Histologic features of allograft livers in patients treated for rejection before biopsy.

Liver biopsy is essential for management in liver transplant patients with clinical features suspicious for acute cellular rejection (ACR). As more patients are transplanted for noninfectious indications, it has become increasingly common for them to receive treatment for presumed ACR before biopsy. The effect of pretreatment on the classic histologic triad of ACR's mixed portal inflammation, endothelialitis, and bile duct damage is not well described. Here we report a retrospective study of 70 liver transplant biopsies performed on 53 patients for suspected ACR between 2018 and 2021. Thirty-seven biopsies had a clinical diagnosis of ACR after biopsy. Pretreatment with steroids, antithymocyte globulin, or other increased immunosuppression was given before biopsy in 17 of 37 cases; 20 not-pretreated cases acted as controls. A representative hematoxylin and eosin-stained slide from each biopsy was reviewed independently in a blinded fashion by 3 hepatic pathologists, graded according to the Banff system, assigned a Rejection Activity Index (RAI), and assessed for other histologic features. We found that pretreated biopsies had significantly less portal inflammation (P < .001), less endothelialitis (P < .001), lower RAI (P < .001), and less prominent eosinophils (P = .048) compared to not-pretreated biopsies. There was no significant difference for the other examined variables, including bile duct inflammation/damage (P = .32). Our findings suggest that portal inflammation and endothelialitis become less prominent with pretreatment, whereas bile duct inflammation/damage may take longer to resolve. When evaluating biopsies for suspected ACR, the finding of bile duct inflammation/damage should raise the possibility of partially treated ACR, even in the absence of endothelialitis and portal inflammation.

Distinguishing Gastrointestinal Leiomyomas From Muscularis Propria in Biopsy Specimens by Differential Expression of S100 Immunohistochemical Stain.

OBJECTIVES: Interpreting small biopsy specimens or fine-needle aspirations of gastrointestinal tract (GI) smooth muscle lesions may be challenging when the differential diagnosis includes leiomyoma vs muscularis propria (MP). We evaluated the utility of S100 staining in distinguishing GI leiomyomas from MP. METHODS: A search was conducted in our laboratory information system for cases of leiomyomas arising within the GI tract (2004-2021). Site-matched controls containing MP were selected (2018-2020). Five high-power fields (hpf) were counted on S100 immunohistochemical stains by two pathologists in the resections and by three different blinded pathologists in the biopsy specimens and analyzed. RESULTS: The median S100 count was 2.5/5 hpf in leiomyoma resection cases (n = 38), which was significantly lower than the median count of 548/5 hpf in MP (n = 19) with a P value of <.0001. The median S100 count in biopsy specimens (n = 16) was 1.2/5 hpf and within the expected range of 1 to 104/5 hpf (minimum-maximum value) established by the leiomyoma resections. S100 counts in the normal MP were significantly higher than those observed in leiomyomas (P < .001). CONCLUSIONS: S100 staining can aid in distinguishing a leiomyoma from MP in the GI tract, which is especially helpful when evaluating cases with limited sampling.

Histologic mimics and diagnostic pitfalls of gastrointestinal endoscopic lifting media, ORISE™ gel and Eleview®.

Synthetic lifting media, ORISE™ gel and Eleview®, are increasingly used in gastrointestinal endoscopy, but neither comparative features nor pitfalls are well-established. Media histopathology, morphologic mimics, and complications are described, along with helpful stains and endoscopist media preference. A 3-year retrospective search was performed. A total of 123 cases (108 endoscopies and 15 subsequent surgeries) were identified. ORISE gel was used in 86 (79.6%), Eleview in 20 (13.9%), and others in 7 (6.5%). ORISE gel was histologically identified in 58.1% (n = 50) of endoscopic specimens and all 15 resections. Eleview media were not detected histologically. ORISE gel mimicked mucin in hematoxylin and eosin-stained biopsies, concerning for adenocarcinoma misdiagnosis and/or upstaging, but did not stain for mucin. Acid-fast bacterial staining highlights ORISE gel for specific and definitive identification. In resections, ORISE evolves into an amorphous eosinophilic material, often with exuberant giant cell reaction and transmural bowel penetration. Polyp formation leads to polypectomy in one patient, and operative lesions concerning for adenocarcinoma resulted in frozen sections in two patients. ORISE gel mimics mucin, malignant masses, amyloid, pulse granulomata, elastofibromas, and infectious granulomata. No significant endoscopist media preference was identified. Recognition of ORISE gel in tissues eliminates multiple pitfalls. Eleview was not detectable, yielded none of the pitfalls seen with ORISE gel, and, on our survey, has equivalent endoscopist acceptance. In this largest published series to date, Eleview is clearly preferable to ORISE gel.

Pulmonary Eosinophilic Granulomatosis with Polyangiitis Has IgG4 Plasma Cells and Immunoregulatory Features.

The immunologic mechanisms promoting eosinophilic granulomatosis with polyangiitis (EGPA) are unclear. To characterize the mechanisms underlying pulmonary EGPA, we examined and compared EGPA paraffin-embedded lung biopsies with normal lung biopsies, using immunostaining, RNA sequencing, and RT-PCR. The results revealed novel type 2 as well as immuneregulatory features. These features included basophils and increased mast cell contents; increased immunostaining for tumor necrosis factor ligand superfamily member 14; sparse mast cell degranulation; numerous forkhead box protein P3 (FoxP3)+ regulatory T cells and IgG4 plasma cells; and abundant arachidonate 15-lipoxygenase and 25-hydroxyvitamin D-1 α hydroxylase, mitochondrial. Significantly decreased 15-hydroxyprostaglandin dehydrogenase [NAD(+)], which degrades eicosanoids, was observed in EGPA samples. In addition, there was significantly increased mRNA for chemokine (C-C motif) ligands 18 and 13 and major collagen genes, IgG4-rich immune complexes coating alveolar macrophages, and increased immunostaining for phosphorylated mothers against decapentaplegic homolog 2/SMAD2, suggesting transforming growth factor-ß activation. These findings suggest a novel self-promoting mechanism of activation of alveolar macrophages by arachidonate 15-lipoxygenase-derived eicosanoids to express chemokines that recruit a combined type 2/immunoregulatory immune response, which produces these eicosanoids. These results suggest that the pulmonary EGPA immune response resembles the immune response to a tissue-invasive parasite infection.

Adaptive optics optical coherence tomography in glaucoma.

Since the introduction of commercial optical coherence tomography (OCT) systems, the ophthalmic imaging modality has rapidly expanded and it has since changed the paradigm of visualization of the retina and revolutionized the management and diagnosis of neuro-retinal diseases, including glaucoma. OCT remains a dynamic and evolving imaging modality, growing from time-domain OCT to the improved spectral-domain OCT, adapting novel image analysis and processing methods, and onto the newer swept-source OCT and the implementation of adaptive optics (AO) into OCT. The incorporation of AO into ophthalmic imaging modalities has enhanced OCT by improving image resolution and quality, particularly in the posterior segment of the eye. Although OCT previously captured in-vivo cross-sectional images with unparalleled high resolution in the axial direction, monochromatic aberrations of the eye limit transverse or lateral resolution to about 15-20 µm and reduce overall image quality. In pairing AO technology with OCT, it is now possible to obtain diffraction-limited resolution images of the optic nerve head and retina in three-dimensions, increasing resolution down to a theoretical 3 µm3. It is now possible to visualize discrete structures within the posterior eye, such as photoreceptors, retinal nerve fiber layer bundles, the lamina cribrosa, and other structures relevant to glaucoma. Despite its limitations and barriers to widespread commercialization, the expanding role of AO in OCT is propelling this technology into clinical trials and onto becoming an invaluable modality in the clinician's arsenal.

Clinical Utility of Optical Coherence Tomography in Glaucoma.

Optical coherence tomography (OCT) has established itself as the dominant imaging modality in the management of glaucoma and retinal diseases, providing high-resolution visualization of ocular microstructures and objective quantification of tissue thickness and change. This article reviews the history of OCT imaging with a specific focus on glaucoma. We examine the clinical utility of OCT with respect to diagnosis and progression monitoring, with additional emphasis on advances in OCT technology that continue to facilitate glaucoma research and inform clinical management strategies.

Prior inpatient admission increases the risk of post-operative infection in hepatobiliary and pancreatic surgery.

BACKGROUND: Hepatobiliary and pancreatic (HPB) operations have a high incidence of post-operative nosocomial infections. The aim of the present study was to determine whether hospitalization up to 1 year before HPB surgery is associated with an increased risk of post-operative infection, surgical-site infection (SSI) and infection resistant to surgical chemoprophylaxis. METHODS: A retrospective cohort study of patients undergoing HPB surgeries between January 2008 and June 2013 was conducted. A multivariable logistic regression model was used for controlling for potential confounders to determine the association between pre-operative admission and post-operative infection. RESULTS: Of the 1384 patients who met eligibility criteria, 127 (9.18%) experienced a post-operative infection. Pre-operative hospitalization was independently associated with an increased risk of a post-operative infection [adjusted odds ratio (aOR): 1.61, 95% confidence interval [CI]: 1.06-2.46] and SSI (aOR: 1.79, 95% CI: 1.07-2.97). Pre-operative hospitalization was also associated with an increased risk of post-operative infections resistant to standard pre-operative antibiotics (OR: 2.64, 95% CI: 1.06-6.59) and an increased risk of resistant SSIs (OR: 3.99, 95% CI: 1.25-12.73). DISCUSSION: Pre-operative hospitalization is associated with an increased incidence of post-operative infections, often with organisms that are resistant to surgical chemoprophylaxis. Patients hospitalized up to 1 year before HPB surgery may benefit from extended spectrum chemoprophylaxis.

Classifying severity of abdominal contour deformities after weight loss to aid in patient counseling: a review of 1006 cases.

BACKGROUND: Abdominal contour deformities after massive weight loss are highly variable, ranging from a mild upper protuberance to multiple rolls. Correction of these deformities is challenging and may require advanced surgical techniques. Evaluating the incidence of patients presenting with various abdominal deformities and the factors influencing these deformities could aid patients undergoing weight loss. METHODS: All massive weight loss patients presenting for abdominal contouring from 2002 to 2012 were reviewed, and abdomens were graded using a modified Pittsburgh Rating Scale. Data collected for each patient included body mass indices, history of bariatric surgery, and type of abdominal contouring surgery. RESULTS: One thousand six patients were evaluated, with a mean age of 44.2 ± 10.5 years. The mean maximum body mass index was 51.7 ± 9.6 kg/m2, mean current body mass index was 30.0 ± 6.4 kg/m2, and mean change in body mass index was 21.7 ± 7.0 kg/m2. Sixty-four percent had a high-grade deformity. Patients with a larger change in body mass index had higher deformity grades (p < 0.001). Patients with higher deformity grades were more likely to undergo a fleur-de-lis abdominoplasty (p < 0.001). CONCLUSIONS: Most patients presenting for body contouring after massive weight loss have high-grade abdominal deformities with multiple rolls. Change in body mass index is positively correlated with deformity grade and more aggressive contouring procedures. Patients interested in massive weight loss should be counseled that, depending on desire for eventual outcomes, more complex procedures may be required to correct the resultant abdominal deformity.

Contribution of intestinal barrier damage, microbial translocation and HIV-1 infection status to an inflammaging signature.

BACKGROUND: Systemic inflammation is a characteristic of both HIV-1 infection and aging ("inflammaging"). Intestinal epithelial barrier damage (IEBD) and microbial translocation (MT) contribute to HIV-associated inflammation, but their impact on inflammaging remains unclear. METHODS: Plasma biomarkers for IEBD (iFABP), MT (LPS, sCD14), T-cell activation (sCD27), and inflammation (hsCRP, IL-6) were measured in 88 HIV-1 uninfected (HIV(neg)) and 83 treated, HIV-1-infected (HIV(pos)) adults from 20-100 years old. RESULTS: Age positively correlated with iFABP (r = 0.284, p = 0.008), sCD14 (r = 0.646, p = <0.0001) and LPS (r = 0.421, p = 0.0002) levels in HIV(neg) but not HIV(pos) subjects. Age also correlated with sCD27, hsCRP, and IL-6 levels regardless of HIV status. Middle-aged HIV(pos) subjects had elevated plasma biomarker levels similar to or greater than those of elderly HIV(neg) subjects with the exception of sCD14. Clustering analysis described an inflammaging phenotype (IP) based on iFABP, sCD14, sCD27, and hsCRP levels in HIV(neg) subjects over 60 years of age. The IP in HIV(neg) subjects was used to develop a classification model that was applied to HIV(pos) subjects to determine whether HIV(pos) subjects under 60 years of age were IP+. HIV(pos) IP+ subjects were similar in age to IP- subjects but had a greater risk of cardiovascular disease (CVD) based on Framingham risk score (p =  0.01). CONCLUSIONS: We describe a novel IP that incorporates biomarkers of IEBD, MT, immune activation as well as inflammation. Application of this novel IP in HIV-infected subjects identified a group at higher risk of CVD.

Increased Escherichia coli-induced interleukin-23 production by CD16+ monocytes correlates with systemic immune activation in untreated HIV-1-infected individuals.

The level of microbial translocation from the intestine is increased in HIV-1 infection. Proinflammatory cytokine production by peripheral antigen-presenting cells in response to translocated microbes or microbial products may contribute to systemic immune activation, a hallmark of HIV-1 infection. We investigated the cytokine responses of peripheral blood myeloid dendritic cells (mDCs) and monocytes to in vitro stimulation with commensal enteric Escherichia coli in peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected subjects and from uninfected controls. Levels of interleukin 23 (IL-23) produced by PBMC from HIV-1-infected subjects in response to E. coli stimulation were significantly higher than those produced by PBMC from uninfected subjects. IL-23 was produced primarily by CD16(+) monocytes. This subset of monocytes was increased in frequency and expressed higher levels of Toll-like receptor 4 (TLR4) in HIV-1-infected individuals than in controls. Blocking TLR4 on total CD14(+) monocytes reduced IL-23 production in response to E. coli stimulation. Levels of soluble CD27, an indicator of systemic immune activation, were elevated in HIV-1-infected subjects and were associated with the percentage of CD16(+) monocytes and the induction of IL-23 by E. coli, providing a link between these parameters and systemic inflammation. Taken together, these results suggest that IL-23 produced by CD16(+) monocytes in response to microbial stimulation may contribute to systemic immune activation in HIV-1-infected individuals.