Histological Signs Of Inflammation Research Articles

OP04 Endoscopic healing in paediatric IBD perpetuates a persistent signature characterized by pathogenic Th17 cells and tissue-associated molecular and microbial drivers of disease

Abstract Background Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBD) in adults and paediatric patients. However, EH may not represent disease clearance. Hence, risk of relapse remains high and treatment discontinuation after reaching EH often results in disease exacerbation. We aimed to identify persistent cellular, molecular and microbial drivers of IBD under EH and longitudinally collected endoscopic biopsies from paediatric patients for analysis of single T-cell and bulk transcriptomics as well as mucosa-associated microbiota. Methods We followed disease trajectories of paediatric IBD patients treated according to international guidelines and collected mucosal biopsies from the terminal ileum (TI) and sigmoid colon (SC) at baseline (T1) and after approximately 3-12 months (T2) to assess EH. Non-IBD controls showed no macroscopic or histologic signs of inflammation. Host RNA and bacterial DNA were simultaneously extracted from single biopsies for bulk RNA-seq, and 16S rRNA seq. A second biopsy was used for isolation of lamina propria mononuclear cells (LPMCs), followed by CD45+, CD3+ cell sorting and single T-cell analysis (10X Genomics). Data were quality controlled and integrated. Results 217 biopsies (135 simultaneous extraction of host RNA and bacterial DNA; 82 single T-cell analysis) from 32 paediatric IBD patients (mean age 13 ± 3.5 years, 21 Crohn’s disease [CD], 11 ulcerative colitis [UC]; T1 = 32, T2 = 32, T > 2 = 6) and 5 non-IBD controls were analysed. Time between T1 and T2 averages 40 ± 22 weeks. At baseline, 15 patients (14 CD, 1 UC) were newly diagnosed and 31/32 patients had active mucosal inflammation. Twenty-two patients (71%) achieved EH at T2 (SES-CED ≤2 and absence of ulcerations), mostly on anti-TNF therapy. One patient (EH at T1) experienced relapsing disease within 10 weeks after discontinuing medication. In the bulk RNA-seq, we identified 299 differential expressed genes (DEGs; corrected p-value <0.05, FC >2.0), such as DUOX2, SAA2-SAA4, FCGR3B and NOS2, that are associated with active IBD and remained upregulated in EH in contrast to non-IBD controls. In addition single cell analysis revealed an IBD-specific pathogenic Th17 cluster that continued to exist in EH and showed high correlation with top DEGs after data integration. 16S rRNA gene seq highlighted highly individual mucosa-associated bacterial profiles and a reduced α-diversity in active and EH compared to non-IBD controls. Conclusion A persisting IBD signature in EH reflects ongoing cellular, molecular and microbial activity in comparison to non-IBD controls despite EH and mucosal regeneration. These markers may provide targets for future or sequential therapies.

Coronary CT angiography for the assessment of atherosclerotic plaque inflammation: postmortem proof of concept with histological validation.

To evaluate the diagnostic utility of multiphase postmortem CT angiography (PMCTA) to detect plaque enhancement as a surrogate marker of inflammation, using fatal coronary plaques obtained from autopsies following sudden cardiac death. In this retrospective study, we included 35 cases (12 women, 34%; median [IQR] age, 52 [11] years), with autopsy-proven coronary thrombosis, histological examination, and multiphase PMCTA. Two radiologists blinded towards histological findings assessed PMCTA for plaque enhancement of the culprit lesion in consensus. Two forensic pathologists determined the culprit lesion and assessed histological samples in consensus. Cases with concomitant vasa vasorum density increase and intraplaque and periadventital inflammation were considered positive for plaque inflammation. Finally, we correlated radiology and pathology findings. All 35 cases had histological evidence of atherosclerotic plaque disruption and thrombosis; 30 (85.7%) had plaque inflammation. Plaque enhancement at multiphase PMCTA was reported in 21 (60%) and resulted in a PPV of 95.2% (77.3-99.2%) and an NPV of 28.6% (17-43.9%). Median histological ratings indicated higher intraplaque inflammation (p = .024) and vasa vasorum density (p = .032) in plaques with enhancement. We found no evidence of a difference in adventitial inflammation between CT-negative and CT-positive plaques (p = .211). Plaque enhancement was found in 2/3 of fatal atherothrombotic occlusions at coronary postmortem CT angiography. Furthermore, plaque enhancement correlated with histopathological plaque inflammation and increased vasa vasorum density. Plaque enhancement on multiphase CT angiography could potentially serve as a noninvasive marker of inflammation in high-risk populations. Phenotyping coronary plaque more comprehensively is one of the principal challenges cardiac imaging is facing. Translating our ex vivo findings of CT-based plaque inflammation assessment into clinical studies might help pave the way in defining high-risk plaque better. • Most thrombosed coronary plaques leading to fatality in our series had histological signs of inflammation. • Multiphase postmortem CT angiography can provide a noninvasive interrogation of plaque inflammation through contrast enhancement. • Atherosclerotic plaque enhancement at multiphase postmortem CT angiography correlated with histopathological signs of plaque inflammation and could potentially serve as an imaging biological marker of plaque vulnerability.

Low-Affinity NMDA Receptor Antagonist Hemantane in a Topical Formulation Attenuates Arthritis Induced by Freund's Complete Adjuvant in Rats.

N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund's Complete Adjuvant (FCA). On day 14 after an FCA injection into the left hind paw, rats with contralateral hind paw edema were selected for further investigation (29/65). They were treated with 5% hemantane gel or 1% diclofenac gel applied locally to hind paws daily for 2 weeks starting 14 days after the FCA injection. Rats with arthritis were examined hind paw edema, hyperalgesia, and motor deficits; their body weight and hematological parameters were recorded. The rats were euthanized on day 28, followed by histological examination of the ankle joint (HE stain). Rats with arthritis exhibited hind paw inflammation and hyperalgesia, motor deficits, changes of hematological parameters, reduced weight gain and spleen hypertrophy. Histological examination of the ankle joint revealed degenerative-dystrophic lesions of the cartilaginous tissue, proliferative inflammation of the synovium, edema and lymphocytic/macrophage infiltration of periarticular tissues. Hemantane gel reduced hind paw edema, pain, motor deficits and histological signs of inflammation; its effect was comparable to diclofenac gel. Hemantane gel alleviates FCA-induced arthritis in rats, and its effect is comparable to diclofenac gel.

Management of pouch related symptoms in patients who underwent ileal pouch anal anastomosis surgery for adenomatous polyposis.

BACKGROUNDAdenomatous polyposis syndromes (APS) patients with ileal pouch anal anastomosis (IPAA) suffer frequent symptoms with scarce signs of inflammation, distinct from ulcerative colitis patients. While the management of pouchitis in ulcerative colitis patients is well established, data regarding response to treatment modalities targeting pouch-related disorders in APS patient population is scarce.AIMTo assess clinical, endoscopic and histologic response to various treatment modalities employed in the therapy of pouch related disorders. METHODSAPS patients who underwent IPAA between 1987-2019 were followed every 6-12 mo and pouch-related symptoms were recorded at every visit. Lower endoscopy was performed annually, recording features of the pouch, cuff and terminal ileum. A dedicated gastrointestinal pathologist reviewed biopsies for signs and severity of inflammation. At current study, files were retrospectively reviewed for initiation and response to various treatment modalities between 2015-2019. Therapies included dietary modifications, probiotics, loperamide, antibiotics, bismuth subsalicylate, mebeverine hydrochloride, 5-aminosalicylic acid compounds and topical rectal steroids. Symptoms and endoscopic and histologic signs of inflammation before and after treatment were assessed. Pouchitis disease activity index (PDAI) and its subscores was calculated. Change of variables before and after therapy was assessed using Wilcoxon signed rank test for continuous variables and using McNemar's test for categorical variables.RESULTSThirty-three APS patients after IPAA were identified. Before treatment, 16 patients (48.4%) suffered from abdominal pain and 3 (9.1%) from bloody stools. Mean number of daily bowel movement was 10.3. Only 4 patients (12.1%) had a PDAI ≥ 7. Mean baseline PDAI was 2.5 ± 2.3. Overall, intervention was associated with symptomatic relief, mainly decreasing abdominal pain (from 48.4% to 27.2% of patients, P = 0.016). Daily bowel movements decreased from a mean of 10.3 to 9.3 (P = 0.003). Mean overall and clinical PDAI scores decreased from 2.58 to 1.94 (P = 0.016) and from 1.3 to 0.87 (P = 0.004), respectively. Analyzing each treatment modality separately, we observed that dietary modifications decreased abdominal pain (from 41.9% of patients to 19.35%, P = 0.016), daily bowel movements (from 10.5 to 9.3, P = 0.003), overall PDAI (from 2.46 to 2.03, P = 0.04) and clinical PDAI (1.33 to 0.86, P = 0.004). Probiotics effectively decreased daily bowel movements (from 10.2 to 8.8, P = 0.007), overall and clinical PDAI (from 2.9 to 2.1 and from 1.38 to 0.8, P = 0.032 and 0.01, respectively). While other therapies had minimal or no effects. No significant changes in endoscopic or histologic scores were seen with any therapy.CONCLUSIONAPS patients benefit from dietary modifications and probiotics that improve their pouch-related symptoms but respond minimally to anti-inflammatory and antibiotic treatments. These results suggest a functional rather than inflammatory disorder.

Quantitative CT imaging analysis to predict pathology features in patients with a congenital pulmonary airway malformation

BackgroundRisk for infection and potential malignant degeneration are the most common arguments for resecting asymptomatic Congenital Pulmonary Airway Malformations (CPAM). We aimed to investigate if CT- imaging characteristics can be used to predict histopathological features, by using an objective quantitative CT scoring method. MethodsArchival CPAM tissue samples were histologically re-assessed and patients who had a pre-operative volumetric CT-scan were included. Lung disease was quantified using the newly-developed congenital lung abnormality quantification(CLAQ) scoring method and obtained percentages were used to predict histopathological signs of inflammation and presence of mucinous proliferation (MP). Because MP is presumed a precursor for mucinous adenocarcinoma in situ (AIS) this method was also used to compare CT-scans of patients with AIS to those with only CPAM. ResultsThirty-three CPAM patients were included of which 13(39%) had histological signs of inflammation and 8(24%) had a MP. Patients with inflammation had a significantly smaller lesion (14% vs 38%) while those with MP had more extensive disease (54%vs17%). Patients with AIS had a significantly smaller lesion compared to CPAM patients (5%vs29%). Significant predictors for inflammation were smaller lesion size and percentage hypodensity within lesions while a larger lesion size and percentage parenchymal hyperdensity (solid lung tissue components) were predictors for MP as well as AIS. ConclusionsSmaller CPAM lesions may be more susceptible to inflammation while larger lesions may be associated with the presence of MP. Parenchymal hyperdensity is found as a predictor for MP as well as AIS and should therefore elicit more extensive gross sampling. Level of evidenceLevel III.

Reshaping of Gut Microbiota in Gilthead Sea Bream Fed Microbial and Processed Animal Proteins as the Main Dietary Protein Source

The present study aimed to unravel the effects of partial (50%; 50LSAqua) and total (100%; 100LSAqua) replacement of fish meal (FM) by a commercial protein source (LSAqua SusPro) made of bacterial and processed animal proteins (PAP) in farmed juveniles of gilthead sea bream (Sparus aurata). The trial lasted 8 weeks, and the feasibility of replacement was assessed in terms of growth performance, histopathological scoring and composition of mucosal adherent microbiota from anterior intestine (AI). Specific growth rates (SGR) of 50LSAqua fish were undistinguishable from the CTRL group, whereas a slight but significant growth impairment was found with the total replacement. Histological signs of inflammation across the intestine were more evident at the highest level of FM replacement, and the total concentration of short chain fatty acids (SCFA) in stripped feces decreased in a dose dependent manner. Illumina sequencing of gut mucosal microbiota yielded a mean of 130,439 reads per sample assigned to 1,567 OTUs at 97% identity threshold. The bacterial richness was similar in all groups, but a significantly higher Simpson diversity index was found in 100LSAqua fish. At the phylum level, Proteobacteria were the most abundant in all groups, whereas Firmicutes decreased and Actinobacteria increased with the FM replacement. At a closer look, pro-inflammatory Gammaproteobacteria of the genus Psychrobacter, and Acinetobacter decreased with FM replacement, whereas the anti-inflammatory Paracoccus, Arthrobacter, and Actinomycetales increased, with a remarkable presence of the Propioniciclava genus in LSAqua groups. The inferred metagenome analysis suggested that these discriminant bacteria could be implicated in a counter-regulatory anti-inflammatory response. It also pointed to an over-representation of mucosal microbes that can potentially be involved in the natural production of antimicrobials in fish fed the experimental diets.

Therapy of antigen-induced arthritis of the temporomandibular joint via platelet-rich plasma injections in domestic pigs

The aim of this animal study was to investigate the effect of platelet-rich plasma (PRP) injections into the temporomandibular joint (TMJ) to treat antigen-induced arthritis AIA.AIA was induced via the application of bovine serum albumin (BSA) into the TMJ. Clear histological signs and protein analysis results indicating inflammation of the TMJ were observed. Afterwards, two PRP injections were performed over an interval of 2 weeks.Concentration levels of the proinflammatory cytokines IL-1β (PRP: 33.7 ± 5.6 pg/mg, untreated: 50.0 ± 2.9 pg/mg; p = 0.04) and TNF-α (PRP: 20.7 ± 2.5 pg/mg, untreated: 31.4 ± 2.7 pg/mg; p = 0.03) were significantly decreased in the PRP-treated joints. A significant reduction in signs of histological inflammation, such as hyperplasia of the synovial membrane, leucocyte infiltration, cartilage surface alterations, and an increase in cartilage-specific glycosaminoglycan content, was observed.This animal study supports the understanding of the underlying effects of PRP treatment in the TMJ, and may enhance novel PRP therapies in the future.

Neonatal lupus with left bundle branch block and cardiomyopathy: a case report

BackgroundCardiac manifestations of neonatal lupus include an array of structural and conduction abnormalities due to placental transference of maternal anti-SSA/Ro and anti-SSB/La autoantibodies. Late-onset neonatal lupus cardiomyopathies, occurring outside the neonatal period, is an infrequently reported manifestation with unknown pathophysiology and poorly defined treatment regimens. Due to the rarity of this condition, additional studies and case reports are required to better understand and manage late-onset neonatal lupus cardiomyopathies.Case presentationA 4-week-old female, born to a mother with known anti-SSA/Ro and anti-SSB/La autoantibodies, presents with classic cutaneous manifestations for neonatal lupus and is found to have left bundle branch block, severely dilated cardiomyopathy with an ejection fraction of 25%, and a thin echogenic dyskinetic ventricular septum. Weekly second trimester and 30-week fetal echocardiograms showed no signs of structural or conduction abnormalities. There were no histologic signs of inflammation on cardiac tissue biopsy. After a complicated hospital course, she was successfully treated with biventricular pacemaker, intravenous immunoglobulin, and plasmapheresis.ConclusionsWe present a case of late-onset neonatal lupus with severe dilated cardiomyopathy, a dyskinetic ventricular septum, and left bundle branch block. To our knowledge, the dyskinetic ventricular septum has never been reported and left bundle branch block is rarely reported in NL. This case further validates the need for long term cardiac follow up for patients born with NL, even if lacking cardiac manifestations in the peripartum period. We characterize a unique presentation of a rare clinical entity, highlighting the diagnostic challenges, and describe a successful treatment course.

Nicotine lowers TNF-α, IL-1b secretion and leukocyte accumulation via nAChR in rat stomach

Inflammatory suppressive effects of nicotine have been observed in inflammatory diseases. We aimed to investigate morphological damage and the changes in TNF-α, IL-1β, and IL-10 expression in the healthy stomach after long-term oral nicotine administration. Nicotine was added to the drinking water of Sprague Dawley rats for 6 weeks. Histological signs of damage, inflammatory cytokines, and nicotinic acetylcholine receptor (nAChR) levels were evaluated in the gastric tissues. There were no histological signs of inflammation in both groups. TNF-α and IL-1β were decreased in the nicotine-treated group. A positive correlation was found between TNF-α levels and infiltrated inflammatory cell count. nAChR levels were increased in the nicotine group. Long term nicotine administration upregulates and activates nAChR. The reduced TNF-α or with high activity nAChR affects the modulation of neutrophil functions and its entry into tissue. Nicotine may deteriorate host defence in non-inflammatory situations.

Multimodal validation of focal enhancement in intracranial aneurysms as a surrogate marker for aneurysm instability

PurposeCircumferential enhancement on MR vessel wall imaging has been proposed as a biomarker of a higher risk of rupture in intracranial aneurysms. Focal enhancement is frequently encountered in unruptured aneurysms, but its implication for risk stratification and patient management remains unclear. This study investigates the association of focal wall enhancement with hemodynamic and morphological risk factors and histologic markers of wall inflammation and degeneration.MethodsPatients with an unruptured middle cerebral artery aneurysm who underwent 3D rotational angiography and 3T MR vessel wall imaging showing focal wall enhancement were included. Hemodynamic parameters were calculated based on flow simulations and compared between enhanced regions and the entire aneurysm surface. Morphological parameters were semiautomatically extracted and quantitatively associated with wall enhancement. Histological analysis included detection of vasa vasorum, CD34, and myeloperoxidase staining in a subset of patients.ResultsTwenty-two aneurysms were analyzed. Enhanced regions were significantly associated with lower AWSS, lower maxOSI, and increased LSA. In multivariate analysis, higher ellipticity index was an independent predictor of wall enhancement. Histologic signs of inflammation and degeneration and higher PHASES score were significantly associated with focal enhancement.ConclusionFocal wall enhancement is colocalized with hemodynamic factors that have been related to a higher rupture risk. It is correlated with morphological factors linked to rupture risk, higher PHASES score, and histologic markers of wall destabilization. The results support the hypothesis that focal enhancement could serve as a surrogate marker for aneurysm instability.

Thermal effects of monopolar electrosurgery detected by real-time infrared thermography: an experimental appendectomy study

BackgroundMonopolar energy (ME) is routinely used in appendectomy. This study aimed to investigate the degree of lateral thermal spread generated by ME and to evaluate the thermal injury sustained by the close-lying tissues.MethodsAppendectomy with a monopolar Maryland dissector was performed in 8 rabbits (at 30 and 60 W power settings). A high-resolution infrared camera was used to record tissue heating during the intervention. After autopsy macroscopic changes were evaluated and tissue samples were subjected to myeloperoxidase (MPO) assay and histological examination.ResultsNo significant differences in the extent of thermal spread, MPO activity and histological signs of inflammation were observed between groups. Regardless of the power settings, the heat spread exceeded 2 cm laterally along the mesoappendix when application time exceeded 3 s. The spread of heat through tubular structures in both groups caused a significant temperature rise in the nearby intestinal loop, resulting in perforation (n = 3) and necrosis (n = 1).ConclusionsApplication time is critical in thermal spread during appendectomy aided by ME. Tubular anatomic structures can enhance thermal injury on distant tissues. The observed effects of ME bear clinical relevance that need further investigation.

Long term Impact of Fat emboli in a Rat Model of Fat Embolism Syndrome

IntroductionFat embolism syndrome (FES) can occur after events that disrupt organ or integument systems such as orthopedic surgery or trauma that result in the release of fat emboli into the microcirculation. The most common clinical manifestation is damage to the lung, brain and retina and induction of systemic inflammation. 86% of patients with FES present with neurological symptoms, often preceding a diagnosis of pulmonary embolism. While the acute symptoms of FES are treated aggressively, the long‐term impact of emboli on the brain is poorly understood. To study the short and long‐term impact of fat emboli (FE) we examined histological changes and distribution of emboli in the brains and lungs 48 hours and 10 weeks after intravenous triolein administration in rats, an established model of fat embolism.Materials and Methods24 anesthetized Sprague Dawley rats (250–330 g) received either 0.2 ml intravenous triolein or saline (N=12 each). Tissue was collected after 48 hours or 10 weeks (N=6/group) snap frozen, sectioned and stained for Oil Red O, and counterstained with Hematoxylin and Eosin. Sections were imaged at 400 x magnification and quantified by two researchers, blind to section identity. Counts were decoded by an independent observer, and statistically compared utilizing a Student’s T‐test.ResultsEmboli were observed in brains of both control and experimental groups. Quantitative evaluation of emboli at 48‐hour post injection did not show any differences in size and location of large diameter emboli (> 25uM) between groups, confirming previous reports. However, an increase in micro emboli (<20uM) of experimental versus control brains was observed. At 10 weeks post injection, a significant increase in the proportion of large emboli was observed in the cerebral cortex, brainstem, in the meningeal spaces and the arteries (p<0.05). These results are in contrast to findings in the lungs where a significant difference in the proportion of large emboli was observed in the lungs at 48 hours and 10‐weeks compared to controls. At both time intervals severe arterial and septal inflammation was observed as previously reported. Histological signs of inflammation were not observed in the brain but moderate meningeal vascular inflammatory reaction was present.ConclusionLarge emboli were observed in the lung at 48 hours and 10 weeks but only micro emboli were observed in the brain at 48 hours with little penetrance of large emboli. At 10 weeks larger emboli were evident in the brain. In contrast to the significant inflammatory reaction observed in lung at both 48 hours and 10‐weeks, only a mild inflammatory reaction was observed in the meninges at 48 hours that was absent at 10‐weeks. Further studies will investigate the long‐term impact of emboli on the anatomical or behavioral outcome in brain.Support or Funding InformationCatherine T. Geldmacher Foundation, St. Louis, MO.; UMKC School of Medicine startup funds (A. Paula Monaghan).

Peculiarities of the wound healing process in the acute period of burn disease depending on the antiseptic used

Background. Burn injury, as one of the most common types of trauma, requires a comprehensive approach to treatment, including surgical and conservative treatment with effective post-burn wound protection. One of the main obstacles to wound healing is purulent-infectious complications, for prevention of which antiseptics are widely used.
 The aim is to study the microbiological, histological features of the wound healing course in the acute period of burn disease with the use of various antiseptics.
 Materials and methods. In the research there were involved 44 patients with burns (burn area 10–20 % of the body surface), treated in the Clinical Center for Thermal Injury and Plastic Surgery of Communal Non-Commercial Enterprise “Vinnytsia Regional Clinical Hospital named after M. I. Pirogov” (2018–2019). Depending on the antiseptic therapy, these patients were divided into three observation groups. Patients in the 1st study group (n = 15; mean age 48.07 ± 12.05 years) were treated with 2.0 % povidone-iodine during dressing. In the 2nd group (n = 15; mean age – 48.53 ± 14.76 years) antiseptic based on 0.02 % decamethoxin was used. In patients of the comparison group (n = 14; mean age – 47.71 ± 12.39 years) a solution of 10.0 % NaCl was administrated for topical wound management. Microbiological assessment of the condition of the wound surface (on 3, 7, 14, 21 days) and histological examination of tissue samples from the bottom of the wound (on 3, 7, 14 days) were carried out by means of standard methods.
 Results. Under the use of antiseptic agents based on 2.0 % povidone-iodine and 0.02 % decamethoxin during the treatment period in patients with burns up to 14 days, an effective reduction in the number of conditionally pathogenic microorganisms on the wound surface to lg (4.8 ± 0.4) and lg (3.06 ± 0.5) CFU/ml, respectively, was registered and it was significantly 1.5 times lower than that based on 10 % sodium chloride solution (p < 0.05). When applying decamethoxin for 14 days at the same time as the eradication of conditionally pathogenic microorganisms, moderate colonization of wounds was registered by representatives of normal skin microbiota (Corynebacterium spp., S. epidermidis). Histologically, there was found that with the use of 2.0 % povidone-iodine, the wound healing course was accompanied by a marked decrease in inflammation signs, as well as a pronounced inhibition of the formation of granulation tissue (10–14 days). The use of 0.02 % decamethoxin was accompanied by the formation of granulation tissue of sufficient maturity for atodermoplasty, in the presence of signs of inflammatory cellular reaction with the presence in the superficial parts of the bottom of the post-burn wounds of the fibrinoid layer, with signs of permanent formation of new hemocapillaries in it, surrounded by a thin argyrophilic mesh. When using a hypertonic sodium chloride solution before autodermoplasty, the granulation tissue had signs of uneven inflammatory cell infiltration. Signs of leukocyte-necrotic tissue changes, fibrinoid-leukocyte layers with fragments of tissue detritus, signs of resuscularization of granulation tissue were recorded.
 Conclusion. Microbiological data strongly suggest the efficacy of 0.02 % decamethoxin and 2.0 % povidone-iodine in reducing microbial wound colonization infection compared to 10.0 % NaCl. The use of antiseptics and hypertonic sodium chloride solution in the acute period of burn disease provides a marked reduction in histological signs of inflammation in the wound with a noticeable positive effect of decamethoxin and 10.0 % NaCl on the formation of granulations and their revascularization compared with povidone-iodine (p < 0.001).

Clinical outcomes after carbon-plate osteosynthesis in patients with distal radius fractures

BackgroundSurgical implant material has changed over time, from metal to stainless steel to titanium. In recent decades a new material, carbon-fibre-reinforced polyether ether ketone, has been introduced. The aim of this study was to assess the clinical and radiological feasibility and functional outcome after treatment of distal radius fractures with this new implant.MethodsInclusion criteria: AO type B distal radius fractures treated with 2.7 mm CF/PEEK plates at one Level 1 trauma centre between 2016 and 2017. Follow-up period 1 year, measurement of range of motion and radiographic assessment, histological analysis of debris only after plate removal.ResultsOut of 112 eligible patients, 10 (8.9%) patients were included. Mean operation time was 65 ± 10 min. Radiographic healing was confirmed by radiologists at 6 weeks follow-up. During one-year follow-up, no adverse events were reported and functionality and patients subjective satisfaction improved significantly (p < 0.05). Only one plate was removed, with no histological signs of inflammation or allergic reaction.ConclusionsThe 2.7 mm CF/PEEK plate osteosynthesis appears to be a reliable and safe implant for certain types of distal radius fracture. Assessment of fracture union is substantially more practical and functionality improved significantly over 1 year.

Antibody-Mediated Delivery of VEGFC Ameliorates Experimental Chronic Colitis.

Crohn's disease (CD) and ulcerative colitis (UC) are two distinct forms of inflammatory bowel disease (IBD) characterized by an expanded lymphatic network with impaired functionality both in mouse models and in human patients. In this study, we investigated whether targeted delivery of the pro-lymphangiogenic vascular endothelial growth factor C (VEGFC) to the site of inflammation may represent a new, clinically feasible strategy for treating IBD. To achieve targeting of inflamed tissue, we developed a fusion protein consisting of human VEGFC fused to the F8 antibody (F8-VEGFC), which specifically binds to the extradomain A (EDA) of fibronectin, a spliced isoform almost exclusively expressed in inflamed tissues. The therapeutic activity of intravenously administered F8-VEGFC, compared to a targeted construct lacking VEGFC (F8-SIP), was investigated in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The presence of EDA fibronectin was detected in both human and mouse inflamed colon tissue. Biodistribution studies of radiolabeled F8-VEGFC revealed a specific accumulation of the antibody in the colon of DSS-administered mice, as compared to an untargeted VEGFC fusion protein (KSF-VEGFC) (binding the irrelevant hen egg lysozyme antigen). Systemic treatment with F8-VEGFC significantly reduced the clinical and histological signs of inflammation, expanded the lymphatic vascular network, reduced the density of immune cells, and also decreased the expression of inflammatory cytokines in the inflamed colon. Overall, these results reveal that administration of F8-VEGFC represents a novel and promising approach for the treatment of IBD.

Soft tissue response to dental implant closure caps made of either polyetheretherketone (PEEK) or titanium

Polyetheretherketone (PEEK) is a popular synthetic thermoplastic polymer for medical applications, but its clinical use suffers from several limitations. Therefore, the aim was to compare the soft tissue response to dental implant closure caps made of PEEK or titanium as evaluated by the occurrence of multinucleated giant cells (MNGCs). Forty-two implants were placed in the maxilla of seven miniature pigs. While commercially pure titanium (Ti) implants had a Ti closure cap, ceramic implants made of either zirconia (Zr) or alumina-toughened zirconia (Zr+Al) received a PEEK closure cap. Histomorphometry was performed to evaluate the number of small and large MNGCs being in contact with the PEEK or the Ti in different compartments of the implant systems. No histological signs of inflammation were noticed, and MNGCs were observed on both PEEK and Ti closure caps and on all three implant types. Significantly higher numbers of MNGCs were found on closure caps made of PEEK than on closure caps made of Ti on the external closure cap surface facing both soft (p=0.0008 for PEEK on Zr and p=0.0016 for PEEK on Zr+Al) and hard tissues (p=0.016 for PEEK on Zr and p=0.003 for PEEK on Zr+Al) as well as in the internal closure cap surface (p=0.014 for PEEK on Zr and p=0.0088 for PEEK on Zr+Al). No statistically significant differences in the number of MNGCs were observed on the three implant types. Significantly more MNGCs were in contact with PEEK than with Ti closure caps.

848 Genes implicated in lipid & metabolic regulation downregulated in CCCA

Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring hair loss in black women. It is characterized by fibrosis out of proportion to the clinical and histologic signs of inflammation, which may lead to progressive end stage fibrosis. Previous work by our group showed that affected CCCA scalp is characterized by an increased expression of profibrotic genes seen in other conditions of aberrant scarring, including hepatic fibrosis. While the cause of this fibrosis is unknown, downregulation of adenosine monophosphate activated protein kinase (AMPK) have been implicated as a primary mediator of hepatic fibrosis, as well as other conditions of scarring. Furthermore, disruption in fatty acid metabolism, including linoleic acid, has been implicated in excess fibrosis including enhanced proliferation of fibroblasts and collagen type I. We performed gene expression microarrays on paired affected and unaffected scalp samples in five patients with CCCA to understand the role of metabolic dysregulation on the pathogenesis of CCCA. Transcriptome-wide analysis of over 20,000 human genes was performed, analyzing all known exons and the 200 (0.9%) most downregulated genes based on fold change were identified. We revealed widespread alterations of genes regulating lipid metabolism (p=2.3 x 10-3) and fatty acid biosynthesis (p=5.3 x 10-6) genes. In particular, the mRNA transcript of protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), which partially encodes for the a subunit of AMPK, was shown to be downregulated by 34% in our CCCA affected scalp compared to the unaffected scalp (p=6.4 x 10-3). Linoleic acid metabolism was also disproportionately dysregulated in our dataset (p=9.1 x 10-3). Our work signifies a potential role that metabolic dysregulation may play in the pathogenesis of CCCA.

Dam characteristics associated with pre-weaning diarrhea in mink (Neovison vison)

BackgroundPre-weaning diarrhea (PWD) in mink, also known as “sticky kits”, is a frequently occurring syndrome in suckling mink kits on commercial mink farms. Outbreaks of PWD result in weakened kits, increased mortality and reduced growth and welfare as well as considerable economic losses for the farmers. The syndrome is regarded as multifactorial with a complex etiology, and studies have focused on associations with environment, management and dam characteristics. The present study was conducted from May to June 2015 and included 70 dams with mink litters with and without PWD. The aims were to examine associations between PWD and mastitis (bacterial infection and histological signs of inflammation or other lesions in the mammary gland), and to examine associations between PWD and other dam-related characteristics (age, litter size, body mass index, and weight and number of active mammary glands of the dam).ResultsUsing multivariable mixed logistic regression analyses with farm id as a random intercept, we found that the odds for PWD in the litter were significantly higher in 1 year old dams versus > 1 year old (OR = 13.3, CI 2.0–90.2, P = 0.01), higher if litter size observed after birth was > 5 kits versus ≤ 5 kits (OR = 16.5, CI 2.2–123.7, P = 0.01), higher if the number of active mammary glands per kit was ≤ 1.5 versus > 1.5 glands per kit (OR = 6.5, CI 1.2–36.0), P = 0.03), and higher in farms with high prevalence of PWD versus low prevalence (OR = 16.8, CI 2.9–97.6, P = 0.002). There were no significant associations between PWD and bacterial infection, histological signs of inflammation or other lesions of the mammary gland, body mass index or weight of mammary gland per kit.ConclusionPre-weaning diarrhea had a statistically significant association with age of the dam, litter size and the number of active mammary glands per kit. However, PWD was not associated with mastitis, body mass index and weight of mammary gland tissue per kit.

Vessel Wall Enhancement in Unruptured Intracranial Aneurysms: An Indicator for Higher Risk of Rupture? High-Resolution MR Imaging and Correlated Histologic Findings.

Recent studies have suggested that wall enhancement of unruptured intracranial aneurysms in high-resolution MR imaging might serve as an imaging biomarker for higher risk of rupture. Histologic studies have revealed a possible association among inflammatory processes, degeneration, and destabilization of the aneurysm wall preceding rupture. Understanding the histologic condition underlying aneurysm wall enhancement could be an important step toward assessing the value of this method for risk stratification. We present our observations of aneurysm wall enhancement in MR vessel wall imaging and underlying histologic changes. We reviewed records of patients with an unruptured middle cerebral artery aneurysm who underwent MR vessel wall imaging before aneurysm clipping. Contrast enhancement of the aneurysm wall was dichotomized into either none/faint or strong. Histologic analysis included myeloperoxidase stain for detection of inflammatory cell invasion and CD34 stain for assessment of neovascularization and vasa vasorum. Thirteen aneurysms were included. Five aneurysms showed strong wall enhancement. Among these, myeloperoxidase staining revealed inflammatory cell infiltration in 4. Three showed neovascularization. In 2 aneurysms, vasa vasorum were present. Seven aneurysms did not show wall enhancement; 1 had only mild enhancement. None of these bore evidence of inflammatory cell invasion or neovascularization, and they all lacked vasa vasorum. Wall enhancement in MR vessel wall imaging is associated with inflammatory cell invasion, neovascularization, and the presence of vasa vasorum. Enhancement does not occur when histologic signs of inflammation are absent. Our results support the hypothesis that MR vessel wall imaging could provide valuable information for risk stratification.

Synergistic effect of copper and arsenic upon oxidative stress, inflammation and autophagy alterations in brain tissues of Gallus gallus

Arsenic or copper is one of the most highly toxic pollution that can cause dysfunction to brains, however, the exact mechanism remains unclear. The aim of the study is to investigate the mechanisms of arsenic or/and copper-induced oxidative stress, inflammation and autophagy in chicken brains and elucidate the interactions between arsenic and copper. A total of 72 1-day-old Hy-line chickens were divided into four groups (18 chickens per group) treated with 30mg/kg arsenic trioxide (As2O3) or/and 300mg/kg copper sulfate (CuSO4) for 12weeks. Histological signs of inflammation were found in the cerebrum, cerebellum and brainstem exposure to arsenic or/and copper. The malondialdehyde (MDA) content were up-regulation, whereas oxidative damage parameters total antioxidant capacity (T-AOC), glutathione (GSH), the inhibition ability of hydroxyl radical (OH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly decreased (P<0.05). The mRNA levels and protein expressions of inflammation markers, such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PTGEs) were significantly increased (P<0.05). The mRNA levels and protein expressions of autophagy markers including phosphatidylinositol 3-kinase (PI3K), Akt, autophagy-related gene 5 (ATG5), microtubule-associated protein light chains 3 (LC3), ATG4B, and Becline1 in different regions of brains were up-regulation (P<0.05), except the mammalian target of rapamycin complex (mTORC). In conclusion, we speculated that arsenic or copper could induce oxidative stress, inflammation and autophagy in chicken brains, and there may have a synergistic effect between copper and arsenic.