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Incorporation of surrounding tissues after implantation of synthetic vascular prostheses potentially varies in accordance with implanted prostheses. To evaluate post-implant tissue incorporation, we examined surgical, histological and ultrastructural findings after implantation in animal models. Three types of commercially available prostheses were tested (Gelweave™; Group G, J Graft SHIELD NEO®; Group J and Triplex®; Group T). Prostheses were implanted into Sprague–Dawley rats subcutaneously or sutured on abdominal aorta of Japanese white rabbits. The tissues were surgically examined for adhesion and were subjected to histological evaluations for cellular and tissue infiltration and ultrastructural observations by scanning electron microscopy (SEM). Group G exhibited less tendency in adhesion formation in early phase (rat: G vs J, P

IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ inflammatory disorder caused by tissue infiltration of lymphocytes with IgG4-secreting plasma cells. Herein, we discuss a case of a patient with IgG4-RD who had involvement of multiple organs: the kidneys, lymph nodes, bone marrow (biopsy performed), lungs, liver, and small intestine (imaging abnormalities). Although several case reports and series of IgG4-RD involving different organ involvement are in the literature, our patient has extensive simultaneous multi-organ involvement. We utilized the four domains (serologic, pathologic, radiologic, and pathologic) as discussed in the new 2019 ACR/EULAR classification criteria to provide a useful framework in considering an alternative tool for IgG4-RD in multi-organ involvement, where biopsy is more invasive and not always accessible. We highlight the findings of each organ involved that increase the likelihood that the patient has IgG4-RD. In our patient, the IgG4-RD classification criteria was fulfilled with total points adding up to 48. Our case meets the classification criteria for IgG4-RD, since at least one organ is involved to meet entry criteria (biopsy proven), no exclusion criteria are present, and the total points are ≥ 20. When such extensive involvement of IgG4-RD occurs, early diagnosis and treatment are recommended to avoid irreversible organ damage and better outcomes.

Local anaesthetics agents (LAA) are used ubiquitously in the medical field and in a wide variety of ways: tissue infiltration, perineural, intra-articular and intravenous. The purpose of this review is to explore the pharmacology of LAAs and to examine the clinical applications for LAAs.

IgG4-related disease (IgG4-RD) is a clinical entity characterized by elevated serum IgG4 and tumor-like inflammation, with tissue infiltration by IgG4 and plasma cells. IgG4-RD is rare, but clinically significant, and its urologic manifestations have been reported in the literature. The present review covers a broad spectrum, describing the pathologies related to the area of urology. In 2003, Terumi Kamisawa was the first to recognize IgG4-RD, characterized by multiorgan lesions in patients with autoimmune pancreatitis and classified as an inflammatory and fibrotic entity with a dense lymphoplasmacytic infiltrate, positive for IgG4.(1–3) It presents in middle-aged patients, between 59-68 years of age, with no clear distribution by sex, (4–6) and has different clinical presentations. The main urologic manifestations are inflammatory pseudotumors and lower urinary tract symptoms. The present article offers a clear, general overview of the disease, encompassing its pathophysiology, diagnosis, and treatment, from the perspective of urology.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome which shares similar pathologic, serologic, and clinical features in the affected organs. Subacute development of a mass or diffuse enlargement of the organ is a common presenting feature. It is more commonly seen in middle-aged or older men. Lymphadenopathy is common in them. Tissue infiltration with lymphoplasmacytic collection, predominantly of IgG4-positive plasma cells, accompanied by “storiform” pattern of fibrosis, obliterative phlebitis, and increased tissue eosinophils are the hallmark histologic findings. Rapid response to systemic steroids is characteristic. If present, the typical cutaneous findings such as papulonodules or plaques in the head-and-neck region may serve as an initial clue to the underlying systemic involvement in IgG4-RD. Hence, dermatologists need to be aware of this entity for early recognition of underlying organ involvement and thus the prompt management.

Functional integration of implanted biomaterials and bioengineered tissues in vivo requires effective and timely vascular ingrowth. While many vascularization strategies rely on delivery of angiogenic growth factors or endothelial cells to promote vascular ingrowth, the effect of physical and architectural features of biomaterials on the vascularization process is less well understood. Microchannels are a simple, accessible architectural feature frequently engineered into 3D biomaterials to promote mass transfer. In this study, the effect of microchannels on the integration and vascularization of 3D porous silk scaffolds was explored over a 14 week period. An array of 508 μm diameter microchannels spanning the length of critically sized, porous silk scaffolds significantly improved tissue ingrowth into the constructs. At week 6, all silk scaffolds (n = 8) with microchannels showed complete tissue infiltration throughout the construct, while only one of eight (12.5%) did so in the absence of microchannels. The presence of microchannels improved silk scaffold vascularization with significantly more vessels per unit area in the presence of microchannels. The vessel size distribution was similar in both scaffold types, but a shift in distribution toward smaller vessels was observed in the presence of microchannels. The blood vessels in silk scaffolds were perfused, functional and connected to the animal's cardiovascular system, as demonstrated by the presence of red blood cells in the vessel lumens, and effective delivery of a contrast agent the vessels inside the scaffold. This study demonstrates the utility of microchannels as a simple architectural feature that significantly improves vascularization and integration of implanted biomaterials.

Background IgG4-related disease (IgG4-RD) is a new syndrome characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells. Here, we evaluated the analytical performance of a new IgG4 assay reagent featuring a wide dynamic range, highly specific monoclonal antibody, and the reversed passive latex agglutination assay and determined the IgG4 reference interval (RI) for the Japanese population. Methods Performance evaluations were conducted on precision, linearity, sensitivity, interference, and method comparison with The Binding Site (TBS) and Siemens reagents. The RI was derived by the parametric method from 619 apparently healthy Japanese 18 to 65 years of age. Results Between-day precisions ranged from 1.99 to 5.52 CV%. Linearity was confirmed up to 5.0 g/l. The limit of quantitation was 0.085 g/l. Interfering substances did not significantly influence values. Method comparison among the 3 reagents yielded correlation coefficients between 0.973 and 0.988. Values for the new reagent matched those of TBS reagent except at a higher concentration range, where reactivity dissociated. The RI was 0.11–1.21 g/l without distinction by sex and age. Conclusion The novel IgG4 assay reagent demonstrated satisfactory analytical performance for clinical use. Because of matched value with TBS reagent at low concentrations, it is possible to use the IgG4-RD cut-off value determined by TBS reagent.

The biophysical properties of biomaterials are key to directing the biological responses and biomaterial integration and function in in situ tissue engineering approaches. We present silk photo-lyogels, a biomaterial format fabricated using a new combinatorial approach involving photo-initiated crosslinking of silk fibroin via di-tyrosine bonds followed by lyophilization to generate 3D, porous lyogels showing physical properties distinct to those of lyophilized silk sponges or silk hydrogels. This fabrication approach allowed introduction of microchannels into 3D constructs via biofabrication approaches involving silk crosslinking around an array of 3D printed photocurable resin pillars to generate parallel channels or around a 3D printed sacrificial thermosensitive gel to generate interconnected channels in a rapid manner and without the need for chemical modification of silk fibroin. The presence of interconnected microchannels significantly improved migration of endothelial cells into 3D photo-lyogels in vitro, and tissue infiltration, photo-lyogel integration, and vascularization when implanted in vivo in a mouse subcutaneous model. Taken together, these findings demonstrate the feasibility and utility of a new combinatorial fabrication approach for generation of silk biomaterials that support cell interactions and implant integration for in situ tissue engineering approaches.

Background Limited research exists examining the influence of age on the passive mechanical properties of the muscle-tendon unit. The purpose of the present study was to 1) investigate the age-related differences in maximum range of motion (MRoM), stretch tolerance (maximal tolerable torque), and the dissipation coefficient (DC), and 2) examine the influence of plantarflexor muscle size and quality on the age-related differences in the DC. Methods Twenty-one young and 14 older men completed a MRoM assessment to determine peak torque (PTpass), energy stored (area under the loading curve), energy restituted (area under the unloading curve), and the DC (normalized hysteresis) from the angle-torque curve. Ultrasonography was used to determine muscle cross-sectional area (CSA) and subcutaneous fat corrected echo intensity (EI) of the gastrocnemii. Findings The PTpass, MRoM, and energy restituted were greater (P ≤ 0.046) in the young men, whereas the DC and EI were greater (P ≤ 0.024) in the older men. When accounting for CSA, differences between groups for the DC remained (P = 0.028), while there were no longer differences between groups when accounting for EI (P = 0.120). PTpass was also strongly related to MRoM (r = 0.755, P Interpretation Older men exhibited lower dorsiflexion MRoM and a greater DC, which may be explained by an altered stretch tolerance and qualitative changes (i.e., non-contractile tissue infiltration) in aged skeletal muscle leading to greater energy dissipated, respectively.

Macrophages are a major component of the immunoresponse. Diversity and plasticity are two of the hallmarks of macrophages, which allow them to act as proinflammatory, anti-inflammatory, and homeostatic agents. Research has found that cancer and many inflammatory or autoimmune disorders are correlated with activation and tissue infiltration of macrophages. Recent developments in macrophage nanomedicine-based disease treatment are proving to be timely owing to the increasing inadequacy of traditional treatment. Here, we review the role of macrophages in nanomedicine-based disease treatment. First, we present a brief background on macrophages and nanomedicine. Then, we delve into applications of macrophages as a target for disease treatment and delivery systems and summarize the applications of macrophage-derived extracellular vesicles. Finally, we provide an outlook on the clinical utility of macrophages in nanomedicine-based disease treatment.

BackgroundLack of reproducibility in gene expression studies has recently attracted much attention in and beyond the biomedical research community. Previous efforts have identified many underlying factors, such as batch effects and incorrect sample annotations. Recently, tissue heterogeneity, a consequence of unintended profiling of cells of other origins than the tissue of interest, was proposed as a source of variance that exacerbates irreproducibility and is commonly ignored.ResultsHere, we systematically analyzed 2,692 publicly available gene expression datasets including 78,332 samples for tissue heterogeneity. We found a prevalence of tissue heterogeneity in gene expression data that affects on average 5-15% of the samples, depending on the tissue type. We distinguish cases of severe heterogeneity, which may be caused by mistakes in annotation or sample handling, from cases of moderate heterogeneity, which are more likely caused by tissue infiltration or sample contamination.ConclusionsTissue heterogeneity is a widespread issue in publicly available gene expression datasets and thus an important source of variance that should not be ignored. We advocate the application of quality control methods such as BioQC to detect tissue heterogeneity prior to mining or analysing gene expression data.

Dermal regenerative templates (DRTs) provide an option for management of complex lower extremity wounds. DRTs may be used to achieve definitive wound closure by serving as a scaffold for local tissue infiltration. Healing with a DRT interface leads to histologic and structural properties similar to native skin. DRTs can be applied over deep wounds with exposed critical structures that may have required a local or free flap. DRTs are a valuable option for lower extremity limb reconstruction.

Langerhans Cell Histiocytosis (LCH) is a rare proliferative disease of the mononuclear phagocyte system, characterised by tissue infiltration of CD1a+ CD207+ histiocytes. The clinical presentation is variable, ranging from unifocal asymptomatic bone involvement to life-threatening multisystem disease, requiring aggressive therapeutic approaches. Intraocular involvement is uncommon and associated to poor visual and general prognosis. Herein, we report a case of LCH in a newborn with ocular and multisystem risk organ involvement, unresponsive to several lines of chemotherapy. Off-label administration of vemurafenib led to dramatic improvement at systemic level; however, chronic sequelae of ocular involvement resulted in poor visual prognosis.

Paraneoplastic syndromes are observed in less than 1% of patients with cancer and include a variety of disorders that do not depend on direct tumor mechanisms, such as tissue infiltration, compress...

Langerhans Cell Histiocytosis (LCH) is a rare proliferative disease of the mononuclear phagocyte system, characterised by tissue infiltration of CD1a + CD207+ histiocytes. The clinical presentation is variable, ranging from unifocal asymptomatic bone involvement to life-threatening multisystem disease, requiring aggressive therapeutic approaches. Intraocular involvement is uncommon and associated to poor visual and general prognosis. We report a case of LCH in a newborn with severe ocular and multisystem risk-organ involvement, unresponsive to several lines of chemotherapy. Off-label administration of vemurafenib led to dramatic improvement at systemic level; however, chronic sequelae of ocular involvement resulted in poor visual prognosis. Intraocular LCH involvement may be asymptomatic and clinical signs delayed, leading to severe complications, especially in newborns and young children. Screening for ocular involvement is essential for early treatment initiation, which can possibly improve the visual outcome. Vemurafenib is effective on systemic involvement, and its role in ocular LCH needs to be evaluated.

Los síndromes eosinofílicos pulmonares (SEP) comprenden un grupo heterogéneo de enfermedades que tienen en común la infiltración eosinofílica en el lavado broncoalveolar y la infiltración tisular en el análisis histopatológico. Se expone un caso correspondiente a una paciente de sexo femenino de 42 años quien consultó por un cuadro clínico agudo de tos, disnea y eosinofilia periférica, con estudios de imágenes torácicas compatibles con con- solidación alveolar en ambos segmentos basales posteriores, la língula y el segmento lateral del lóbulo medio derecho. Se descartó parasitosis, infección por micobacterias, infección por hongos, virus respiratorios, patología oncológica y reumatológica. La biopsia de pulmón mostró un engrosamiento de los tabiques interalveolares con proliferación celular de linfo- citos e histiocitos con hiperplasia alveolar, neumocitos atípicos y ocupación difusa de la luz con abundantes eosinófilos. El curso clínico y los hallazgos histopatológicos confirman el diagnóstico de neumonía eosinofílica aguda (NEA).

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413-420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77-84, 2019. © 2019 Wiley Periodicals, Inc.

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptom...

The efficacy of macrophage- mediated inflammatory response relies on the coordinated expression of key factors, which expression is finely regulated at both transcriptional and post-transcriptional level. Several studies have provided compelling evidence that microRNAs play pivotal roles in modulating macrophage activation, polarization, tissue infiltration, and resolution of inflammation. In this review, we highlight the essential molecular mechanisms underlying the different phases of inflammation that are targeted by microRNAs to inhibit or accelerate restoration to tissue integrity and homeostasis. We further review the impact of microRNA-dependent regulation of tumor-associated macrophages and the relative implication for tumor biology.

Background:Elevated serum IgG4 (sIgG4) and IgG4+ plasma cell tissue infiltration are outstanding features of IgG4-related disease (IgG4-RD). However, elevated IgG4 is not specific for IgG4-RD. Our previous study reported elevated sIgG4 in 46% of rheumatoid arthritis (RA) patients (Mediators Inflamm 2014). Whether synovium from RA patients show similar characteristics of IgG4-RD and how about the clinical characteristics of RA patients with IgG4-related synovitis have not been reported yet.Objectives:To explore the serum and synovial IgG4 level and their correlation with disease indicators in RA.Methods:Active RA patients who underwent needle synovial biopsy with qualified synovium tissue were recruited. Demographic and clinical data were collected simultaneously. Synovium tissue were stained with H&E for Krenn synovitis score and immunohistochemistry for positive cell densities of CD20, CD38, IgG and IgG4. Serum IgG4 level was detected by immunonephelometry.Results:Among 96 RA patients recruited, 74 (77.1%) were female, the median age was 55.0 (46.0~61.0) years, disease duration was 42.0 (12.0~120.0) months and SDAI was 31.2 (22.1~42.8).The median sIgG4 was 1.38 (0.86~2.42) g/L and 49(51.0%) patients had elevated sIgG4. Compared with those with normal sIgG4, RA patients with elevated sIgG4 had significantly higher levels of PrGA [7 (5~8) vs. 6 (4~7)], ESR [90 (64~116) mm/h vs. 61 (38~75) mm/h], CRP [46.20 (17.20~74.20) mg/L vs. 18.90 (9.46~49.20) mg/L], DAS28-ESR [6.3 (5.6~7.4) vs. 5.7 (4.7~6.4)], SDAI [34.2 (25.3~48.8) vs. 27.8 (18.9~35.9)] and HAQ-DI [1.70 (0.61~2.28) vs. 0.88 (0.40~1.75), all P2 vs. 1020(354~1777) /mm2], IgG4+ plasma cells [106 (39~249) /mm2 vs. 68 (3~123) /mm2], and higher ratio of IgG4+/IgG+ plasma cells [26.3 (15.5~38.0) % vs. 15.2 (0.9~24.7) %, all PThe median IgG4+ plasma cells count was 83 (10~192) /mm2 and median ratio of IgG4+/IgG+ plasma cells was 19.1 (8.4~31.5)%. Both of them correlated positively with ESR, CRP and sIgG4 (r=0.216~0.394, all P10/HPF, who had significant higher ESR [86 (50~109) mm/h vs. 65 (40~84) mm/h] and CRP [43.35 (16.93~77.85) mg/L vs. 26.15 (9.54~52.53) mg/L, both P40%, and 11 (11.5%) patients with both IgG4+ plasma cells >10/HPF and IgG4+/IgG+ plasma cells ratio >40% (IgG4-related synovitis). RA patients with IgG4-related synovitis had significant higher ESR than the others [106 (53~125) mm/h vs. 69 (41~91) mm/h, PThere were 10 (10.4%) patients showing elevated sIgG4 and IgG4-related synovitis. Four patients completed 1-year follow-up and all of them achieved remission at 6th month (SDAI≤3.3, Figure 1). Only one patient had radiographic progression at 12th month.Figure 1.Dynamic disease activity of 4 RA patients with elevated sIgG4 and IgG4-related synovitis during 1-year follow-up.Conclusion:IgG4-related synovitis can be found in RA patients. Their clinical significance in disease characteristics and outcomes are worth further study.Acknowledgements:This work was supported by National Natural Science Foundation of China (no. 81971527, 81801606 and 81801605), Guangdong Natural Science Foundation (no. 2018A030313541 and 2018A030313690), Guangdong Medical Scientific Research Foundation (no. A2018062), Guangdong Basic and Applied Basic Research Foundation (no. 2019A1515011928 and 2020A1515110061), and Science and Technology Program of Guangzhou (no. 201904010088).Disclosure of Interests:None declared

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing–remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids.In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD.With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centres.

A long-acting buprenorphine subdermal implant, Probuphine, was approved by the Food and Drug Administration (FDA) in May 2016, for the maintenance treatment of patients with opioid-use disorder. Long-acting implants offer the potential benefits of improved medication adherence, consistent daily dosing, and reduced risk of medication diversion. Sets of 4 implants are typically inserted for a period of 6 months and then removed. Similar technology has been successfully utilized in implantable formulations of birth control medications; however, there is currently little clinical experience involving buprenorphine implants that have remained in the body for extended periods of time. This is a case report involving an early clinical study subject who had been lost to follow-up at the time of the original study because of incarceration. Despite the protracted duration of time since initial implantation, all 4 implants remained easily palpable, and displayed little physical deterioration or tissue infiltration. All implants were able to be removed using the standard explant technique of midline incision and limited tissue dissection. While extending length of treatment beyond the indicated 6-month period is not being espoused, this case demonstrates that although situations may arise where implants may remain in an individual for longer than the intended dosing period, implants may be removed safely despite remaining implanted for longer than intended.

Objective: To explore the imaging features of local recurrences (LRs) based on magnetic resonance imaging (MRI) after oncological orthopaedic surgery with prosthesis reconstruction. Methods: A total of 78 cases totalling 157 scans were retrospectively reviewed. Patients with nodule/mass-like signals were retrospectively classified into LR, infectious pseudotumour, and asymptomatic pseudotumour according to clinicopathological data. LRs were histologically confirmed, and the patients without recurrences were followed up for at least 2 years. Mass size distribution and radiological characteristics were analysed for differential diagnosis of the LR versus pseudotumour. Results: Thirty-three of 78 cases were positive with nodule/mass-like signal findings on the post-operative MRI images. By analysing the size distribution, we found that masses >2.1 cm (14) were almost attributable (98% specificity) to LRs and mostly (84.6%) timely treated. Contrarily, masses ≤2.1 cm (19) are challenging for differential diagnosis of LRs versus pseudotumour and were undertreated in five of the nine LR cases. MRI characteristics of masses ≤2.1 cm were found to be highly heterogeneous, with solid appearance, adjacent infiltration, and less peritumour oedema being significant indicators for LRs (P＜0.05). Receiver operating characteristic curve showed area under curve of 0.93 for this predictive model. Conclusions: For the post-operative MRI surveillance of oncological orthopaedic surgery with prosthesis reconstruction, a mass larger than 2.1 cm was highly specific for recurrence. When a mass was smaller than 2.1 cm, more solid property, more adjacent tissue infiltration, and less muscular oedema indicated recurrence rather than a benign mass. The translational potential of this article: There has been very little data associated with the post-operative magnetic resonance imaging features indicating recurrence in patients with malignant bone sarcoma after prosthesis replacement. This study could help develop diagnostic features of magnetic resonance imaging for differentiating recurrence from benign changes in these patients after prosthesis replacement. Keywords: Magnetic resonance imaging, Post-operative, Prosthesis, Recurrence

White blood cells (WBCs) are a major component of immunity in response to pathogen invasion. Neutrophils are the most abundant WBCs in humans, playing a central role in acute inflammation induced by pathogens. Adhesion to vasculature and tissue infiltration of neutrophils are key processes in acute inflammation. Many inflammatory/autoimmune disorders and cancer therapies have been found to be involved in activation and tissue infiltration of neutrophils. A promising strategy to develop novel targeted drug delivery systems is the targeting and exploitation of activated neutrophils. Herein, a new drug delivery platform based on neutrophils is reviewed. There are two types of drug delivery systems: neutrophils as carriers and neutrophil-membrane-derived nanovesicles. It is discussed how nanoparticles hijack neutrophils in vivo to deliver therapeutics across blood vessel barriers and how neutrophil-membrane-derived nanovesicles target inflamed vasculature. Finally, the potential applications of neutrophil-based drug delivery systems in treating inflammation and cancers are presented.

When infecting the lungs with Mycobacterium avium of B6 line mice genetically susceptible to this infection the compact aggregates (follicles) of B-lymphocytes are formed with the peak at the 11-13th week after the infection. Physiological role of these cellular accumulations remained unclear. Having applied segregative genetic analysis to allele conglutination of Slc11a1 gene with two signs – quantity of mycobacteria and accumulation of B-cellular follicles to the F2 mice from crossing (В6 × I/St), one managed to find out that the quantity and size of follicles directly correlate with M. avium replication in the lungs. Thus this type of the lung tissue infiltration does not protect the host from infection and it is a pathogenic factor.

The filling of wound cavities with new tissue is a challenge. We previously reported on the physical properties and wound healing kinetics of prefabricated, gas-blown polyurethane (PUR) scaffolds in rat and porcine excisional wounds. To address the capability of this material to fill complex wound cavities, this study examined the in vitro and in vivo reparative characteristics of injected PUR scaffolds employing a sucrose porogen. Using the porcine excisional wound model, we compared reparative outcomes to both preformed and injected scaffolds as well as untreated wounds at 9, 13, and 30 days after scaffold placement. Both injected and preformed scaffolds delayed wound contraction by 19% at 9 days and 12% at 13 days compared to nontreated wounds. This stenting effect proved transient since both formulations degraded by day 30. Both types of scaffolds significantly inhibited the undesirable alignment of collagen and fibroblasts through day 13. Injected scaffolds were highly compatible with sentinel cellular events of normal wound repair cell proliferation, apoptosis, and blood vessel density. The present study provides further evidence that either injected or preformed PUR scaffolds facilitate wound healing, support tissue infiltration and matrix production, delay wound contraction, and reduce scarring in a clinically relevant animal model, which underscores their potential utility as a void-filling platform for large cutaneous defects. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1679-1690, 2016.

Xanthoma cystitis of urinary bladder is a rare entity and may present as an intravesical mass. A 38-year-old female presented with abdominal pain and imaging was done which was suggestive of a malignant mass with surrounding tissue infiltration. Partial cystectomy was performed, and histological examination of the mass showed xanthomatous cystitis.

In recent years, the thermally induced phase-separation process has been used extensively to form porous materials, such as scaffolds and drug delivery devices with pore sizes ranging from the nano- to the micro-scale. This chapter discusses the methods that are used for creating these tissue-engineering scaffolds. Porous tissue scaffolds offer several benefits for the engineering of soft tissues. These most notably include infiltration of cells and tissue infiltration together with vascularization to support perfusion of oxygen and nutrients. Phase separation technologies provide an almost unrivaled platform for the manufacture of 3D tissue-engineering scaffolds. The manufacturing processes involved are often relatively low cost, scalable, and compatible with a wide range of materials. The structural features attained can be designed to resemble native extracellular matrix or provide novel substrates capable of stimulating specific cellular responses. These attributes are likely to result in the technology being increasingly utilized as the field of tissue engineering and regenerative medicine grows.

Highlights • The patient was a 59-year-old man presenting with a swollen right submandibular gland. Laboratory tests revealed IgG4 levels of 176 mg/dl (reference range: 4.8–105). • Histological examination of the submandibular gland showed an adenoid cystic carcinoma with lymphocytic infiltration containing many IgG4-positive plasma cells in the tumor stroma., Introduction Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory condition associated with elevated serum IgG4 levels and tissue infiltration by IgG4-expressing plasma cells. We present a case of adenoid cystic carcinoma (ACC) of the submandibular gland with possible involvement of IgG4-RD. Presentation of case The patient was a 59-year-old man presenting with a swollen right submandibular gland. Laboratory tests revealed IgG4 levels of 176 mg/dl (reference range: 4.8–105). An initial open biopsy for histological diagnosis showed chronic sialadenitis. The region was monitored on an outpatient basis, and finally the right submandibular was totally resected because malignant tumor could not be excluded. Histological examination of the submandibular gland showed an ACC with lymphocytic infiltration containing many IgG4-positive plasma cells in the tumor stroma. Discussion We have described a case that indicated a possible involvement of ACC with IgG4-RD. This allows us to speculate that longstanding IgG4-RD may progress to malignancy or infiltration of IgG4-positive plasma cells through the signals of tumor stimuli. Further investigations are required to determine the potential pathogenic mechanism underlying this unique tumor. Conclusion This case underscores that caution is needed in the diagnosis of masses with high serum IgG4 levels, as the differential diagnosis includes malignancy.

IgG4-related disease, a newly described immune-mediated disorder with tissue infiltration of IgG4-positive plasma cells, has been reported in nearly every organ. In the kidney, it manifests as IgG4-related tubulointerstitial nephritis (TIN) but may also present as membranous nephropathy. We report a patient with IgG4 renal disease who had membranous nephropathy as well as TIN.

Bone-patellar tendon-bone (BPTB) autografts are the gold standard for anterior cruciate ligament (ACL) reconstruction because the bony ends allow for superior healing and anchoring through bone-to-bone regeneration. However, the disadvantages of BPTB grafts include donor site morbidity and patellar rupture. In order to incorporate bone-to-bone healing without the risks associated with harvesting autogenous tissue, a biodegradable and synthetic tri-component graft was fabricated, consisting of porous poly(1,8-octanediol-co-citric acid)-hydroxyapatite nanocomposites (POC-HA) and poly(l-lactide) (PLL) braids. All regions of the tri-component graft were porous and the tensile properties were in the range of the native ACL. When these novel grafts were used to reconstruct the ACL of rabbits, all animals after 6 weeks were weight-bearing and showed good functionality. Histological assessment confirmed tissue infiltration throughout the entire scaffold and tissue ingrowth and interlocking within the bone tunnels, which is favourable for graft fixation. In conclusion, this pilot study suggests that a tri-component, biodegradable graft is a promising strategy to regenerate tissue types necessary for ACL tissue engineering, and provides a basis for developing an off-the-shelf graft for ACL repair. Copyright © 2014 John Wiley & Sons, Ltd.

Case report We report the case of a 48 year-old male with bilateral involvement of the salivary and lacrimal glands, which was diagnosed as Mikulicz's disease by incisional biopsy of the affected lacrimal glands, which was completely resolved after corticosteroid treatment. Discussion Sclerosing sialadenitis and/or dacryoadenitis are chronic inflammatory diseases that are currently classified into IgG4-related diseases. Specifically, Mikulicz's disease is defined by a persistent and symmetrical swelling of the lacrimal and salivary glands together with elevated serum concentration of IgG4 and tissue infiltration by IgG4 (+) plasma cells.

The scapholunate interosseous ligament (SLIL) is a frequently torn wrist ligament, and current surgical options for SLIL tears are suboptimal. This research aims to develop a novel multiphasic bone-ligament-bone scaffold (BLB) with a porous interface using 3D-printing and cell sheet technology for the reconstruction of the dorsal scapholunate interosseous ligament. The BLB comprises two bone compartments bridged by aligned polycaprolactone fibers mimicking the architecture of the native tissue. Mechanical testing of the BLBs shows their ability to withstand physiological forces. Combination of the BLB with human bone marrow mesenchymal stem cell sheet demonstrates that the harvesting did not compromise cell viability, while allowing homogeneous distribution in the ligament compartment. The BLBs are loaded with cell sheets and bone morphogenetic protein-2 in the ligament and bone compartment respectively prior to ectopic implantation into athymic rats. The histology demonstrates rapid tissue infiltration, high vascularization, and more importantly the maintenance of the compartmentalization as bone formation remains localized to the bone compartment despite the porous interface. The cells in the ligament compartment become preferentially aligned, and this proof-of-concept study demonstrates that the BLB can provide sufficient compartmentalization and fiber guiding properties necessary for the regeneration of the dorsal SLIL.

IgG4-related disease (IgG4-RD) is a recently recognized disease covering different fibroinflammatory disorders with common histopathological findings. Virtually all organs can be involved, but the most frequently affected are the pancreas, biliary tree, salivary and lacrimal glands, retroperitoneum and aorta, kidneys, and lymph nodes. Several organ manifestations can develop simultaneously or metachronously in the same patient. Clinical and radiological presentation is usually pseudotumoral with mass-forming lesions, requiring rigorous clinicopathological examination and exclusion of alternative diagnoses, especially cancer. Histopathological abnormalities include polyclonal lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. Immunohistology shows tissue infiltration by numerous IgG4-positive plasma cells. Steroids are usually dramatically effective in this condition, but relapses are frequent and second-line treatments are often necessary. An overview on main clinical and therapeutic aspects of the disease is proposed in this chapter.