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Cytotherapy Aug 2023The most clinically trialed cells, mesenchymal stromal cells (MSCs), are now known to mainly exert their therapeutic activity through paracrine secretions, which include...
The most clinically trialed cells, mesenchymal stromal cells (MSCs), are now known to mainly exert their therapeutic activity through paracrine secretions, which include exosomes. To mitigate potential regulatory concerns on the scalability and reproducibility in the preparations of MSC exosomes, MSC exosomes were produced using a highly characterized MYC-immortalized monoclonal cell line. These cells do not form tumors in athymic nude mice or exhibit anchorage-independent growth, and their exosomes do not carry MYC protein or promote tumor growth. Unlike intra-peritoneal injections, topical applications of MSC exosomes in a mouse model of IMQ-induced psoriasis alleviate interleukin (IL)-17, IL-23 and terminal complement complex, C5b9 in psoriatic skin. When applied on human skin explants, fluorescence from covalently labeled fluorescent MSC exosomes permeated and persisted in the stratum corneum for about 24 hours with negligible exit out of the stratum corneum into the underlying epidermis. As psoriatic stratum corneums are uniquely characterized by activated complements and Munro microabscesses, we postulated that topically applied exosomes permeate the psoriatic stratum corneum to inhibit C5b9 complement complex through CD59, and this inhibition attenuated neutrophil secretion of IL-17. Consistent with this, we demonstrated that assembly of C5b9 on purified human neutrophils induced IL-17 secretion and this induction was abrogated by MSC exosomes, which was in turn abrogated by a neutralizing anti-CD 59 antibody. We thus established the mechanism of action for the alleviation of psoriatic IL-17 by topically applied exosomes.
Topics: Animals; Mice; Humans; Exosomes; Interleukin-17; Mice, Nude; Reproducibility of Results; Psoriasis; Mesenchymal Stem Cells
PubMed: 37115163
DOI: 10.1016/j.jcyt.2023.03.015 -
Head and Neck Pathology Mar 2022Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth... (Review)
Review
Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth pattern resembling rabbit burrows (cuniculi). With less than 75 cases reported in the head and neck, the clinical and pathologic spectrum of this entity remains poorly understood. A retrospective review of the clinical and pathologic features of archival cases of oral CC was performed. A total of six cases of oral CC were identified. Age ranged from 25-77 years; the male-to-female ratio was 5:1. All patients had a long-standing history of tobacco and betel-quid consumption. The tumors were distributed in the gingivobuccal sulcus (n = 2), the tongue (n = 2), buccal mucosa (n = 1), and the palate (n = 1). Histology in all cases typically revealed a tumor composed of well-differentiated squamous epithelium, devoid of atypia, lining deeply infiltrative, large-sized, branching, keratin-filled cavities, resembling rabbit-burrows. Dense lymphocytic infiltrates and discharging micro-abscesses were regular features. Underlying bone invasion and lymph node metastasis were observed in 1 patient. One patient with a tongue tumor developed locoregional recurrence at 10 months while none developed distant metastasis. Oral CC is a rare and under-recognized variant of SCC with locally aggressive behavior. Lack of familiarity with this variant exacerbated by the absence of cytologic anaplasia makes CC susceptible to multiple negative biopsies and erroneous diagnoses. Awareness of this clinicopathologic entity is essential to allow its accurate diagnosis and optimal management.
Topics: Animals; Bone Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Female; Humans; Male; Mouth Neoplasms; Neoplasm Recurrence, Local; Rabbits; Tongue Neoplasms
PubMed: 34076846
DOI: 10.1007/s12105-021-01340-6 -
The American Journal of Surgical... Oct 2021Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and...
Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.
Topics: Adult; Aged; Anti-Bacterial Agents; Diagnosis, Differential; Female; Granuloma, Plasma Cell; Humans; Liver; Liver Abscess; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Treatment Outcome; Young Adult
PubMed: 34334689
DOI: 10.1097/PAS.0000000000001767 -
Journal of Education & Teaching in... Jan 2023Small bowel diverticulitis is an uncommon subset of acute diverticulitis and can mimic many other intra-abdominal processes. As a result, imaging modalities such as...
UNLABELLED
Small bowel diverticulitis is an uncommon subset of acute diverticulitis and can mimic many other intra-abdominal processes. As a result, imaging modalities such as ultrasound and computed tomography (CT) scan are especially important for timely recognition of diverticulitis and can expedite diagnosis and treatment and reduce complications. In the case described in this report, an 81-year-old male with history of esophageal cancer and recurrent diverticulitis with history of multiple bowel resections presented to the emergency department (ED) with right lower quadrant abdominal pain and constipation. Findings on ultrasound were suggestive of diverticulitis, and findings on CT of the abdomen and pelvis showed ileitis with phlegmon and micro-abscess suspicious for small bowel diverticulitis. ED providers should familiarize themselves with ultrasound findings of diverticulitis and be aware that diverticulitis can also present in the small bowel. Treatment of small bowel diverticulitis is similar to colonic diverticulitis.
TOPICS
Ileitis, small bowel diverticulitis, abdominal ultrasound.
PubMed: 37465035
DOI: 10.21980/J8F078 -
Biomedical Optics Express Apr 2022A technology capable of high-resolution, label-free imaging of subtle pathology during colonoscopy is imperative for the early detection of disease and the performance...
A technology capable of high-resolution, label-free imaging of subtle pathology during colonoscopy is imperative for the early detection of disease and the performance of accurate biopsies. While colonoscopic OCT has been developed to visualize colonic microstructures beyond the mucosal surface, its clinical potential remains limited by sub-optimal resolution (∼6.5 µm in tissue), inadequate imaging contrast, and a lack of high-resolution OCT criteria for lesion detection. In this study, we developed an ultrahigh-resolution (UHR) colonoscopic OCT and evaluated its ability to volumetrically visualize and identify the pathological features of inflammatory bowel disease (IBD) in a rat model. Owing to its improved resolution (∼1.7 µm in tissue) and enhanced contrast, UHR colonoscopic OCT can accurately delineate fine colonic microstructures and identify the pathophysiological characteristics of IBD in vivo. By using a quantitative optical attenuation map, UHR colonoscopic OCT is able to differentiate diseased tissue (such as crypt distortion and microabscess) from normal colonic mucosa over a large field of view in vivo. Our results suggest the clinical potential of UHR colonoscopic OCT for in vivo assessment of IBD pathology.
PubMed: 35519259
DOI: 10.1364/BOE.453396 -
Oncology Letters Jan 2020Granulomatous lobular mastitis (GLM) and mammary duct ectasia (MDE) are inflammatory diseases. However, only a limited number of studies have focused on characterizing...
Granulomatous lobular mastitis (GLM) and mammary duct ectasia (MDE) are inflammatory diseases. However, only a limited number of studies have focused on characterizing their clinicopathological features. The aim of the present study was to investigate the etiology, clinicopathological characteristics and diagnosis of GLM and MDE. The clinical information and treatment of 118 female patients with pathologically-proven GLM or MDE were retrospectively analyzed in the present study. A total of 29 cases had GLM, 77 had MDE and 12 had GLM accompanied by MDE. GLM tends to occur in patients who have had their last birth within 5 years and are usually <40 years of age. GLM masses were usually larger than MDE masses and suppurated or ulcerated more easily. Histopathologically, GLM was characterized by a significant granulomatous inflammatory reaction centered on lobules. Compared with MDE, GLM had a higher incidence of granuloma and microabscess formation within the lobules and surrounding tissue. More multinucleated giant cells within granuloma were observed in patients with GLM than in those with MDE, while MDE was characterized by significant dilatation of the duct terminals and inflammatory changes in the duct wall and periductal tissues. When compared with patients with GLM, foam cells within the duct epithelium or surrounding stroma were more common in patients with MDE. The present study demonstrated that GLM and MDE had distinct clinicopathological characteristics. Further research is required in order to identify more appropriate treatment strategies for these specific types of breast inflammation.
PubMed: 31885718
DOI: 10.3892/ol.2019.11156 -
Journal of Clinical and Experimental... Jan 2023Sporotrichosis is an uncommon subacute or chronic infection caused by Sporothrix spp. In some urban areas of Latin America, sporotrichosis has been considered an...
Sporotrichosis is an uncommon subacute or chronic infection caused by Sporothrix spp. In some urban areas of Latin America, sporotrichosis has been considered an emergent cosmopolitan disease of zoonotic transmission by domestic cats. There are four different clinical forms of the disease: fixed cutaneous, lymphocutaneous, multifocal or disseminated cutaneous, and extracutaneous. The oral mucosa is rarely involved, usually as unspecified chronic ulcers in the context of multifocal or disseminated cutaneous form of systemic sporotrichosis. Microscopical features include chronic granulomatous inflammation containing microabscesses and fungal hyphae positive for Periodic acid Schiff and silver-based stains. The diagnosis of sporotrichosis is usually based on culture detection and strict correlation of clinical, microscopical and laboratorial data. We herein contribute with two additional illustrative cases of oral manifestation of sporotrichosis in immunocompromised patients from an endemic urban area from Rio de Janeiro-Brazil. Sporotrichosis, ulcer, oral cavity, immunosuppression.
PubMed: 36755684
DOI: 10.4317/jced.59040 -
Journal of Inflammation Research 2024Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from...
PURPOSE
Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies.
PATIENTS AND METHODS
Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration.
RESULTS
PDM patients had a higher median age compared to GLM patients (38 vs 32, p<0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p<0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p<0.001), ductal wall thickening (47.93% vs 1.75%, p<0.001), and ductal rupture (44.63% vs 5.26%, p<0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p<0.001), microabscess (68.42% vs 28.93%, p<0.001), and lipid vacuole (40.35% vs 8.26%, p<0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy.
CONCLUSION
PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.
PubMed: 38895142
DOI: 10.2147/JIR.S464585 -
Respiratory Physiology & Neurobiology Mar 2023Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of... (Review)
Review
Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of standardized protocols assuming similarity to severe acute respiratory syndrome (SARS-CoV-2). Understanding the histopathological and functional patterns is essential to better understand the pathophysiology of COVID-19 and then develop new therapeutic strategies. Epithelial and endothelial cell damage can result from the virus attack, thus leading to immune-mediated response. Pulmonary histopathological findings show the presence of Mallory bodies, alveolar coating cells with nuclear atypia, reactive pneumocytes, reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates, micro-abscesses, microthrombus, hyaline membrane fragments, and emphysema-like lung areas. COVID-19 patients may present different respiratory stages from silent to critical hypoxemia, are associated with the degree of pulmonary parenchymal involvement, thus yielding alteration of ventilation and perfusion relationships. This review aims to: discuss the morphological (histopathological and radiological) and functional findings of COVID-19 compared to acute interstitial pneumonia, acute respiratory distress syndrome (ARDS), and high-altitude pulmonary edema (HAPE), four entities that share common clinical traits, but have peculiar pathophysiological features with potential implications to their clinical management.
Topics: Humans; COVID-19; SARS-CoV-2; Altitude; Pulmonary Edema; Pneumonia; Respiratory Distress Syndrome
PubMed: 36460252
DOI: 10.1016/j.resp.2022.104000 -
Tropical Medicine and Health 2020() is a facultative protozoan parasite implicated in amoebic liver abscesses (ALA), the most common extraintestinal manifestation of this infection. is endemic to... (Review)
Review
() is a facultative protozoan parasite implicated in amoebic liver abscesses (ALA), the most common extraintestinal manifestation of this infection. is endemic to sub-tropical and tropical countries and has been a major public health concern in northern Sri Lanka (SLK) for the last three decades. This has been attributed to a multitude of factors such as poor sanitation, hygiene, male sex, middle age, overcrowding, unsanitary practices in the production of indigenous alcoholic beverages, and alcohol consumption. Additionally, while rates of have declined substantially throughout the rest of the island, largely due to better infrastructure, it remains pervasive in the northern peninsula, which is generally less developed. Infection arises primarily from fecal-oral transmission through the consumption of contaminated drinking water containing cysts. Upon ingestion, cysts multiply into trophozoites and colonize the host colonic mucosa using lectin and cysteine proteases as virulence factors, leading to host invasion. Symptoms occur along a spectrum, from asymptomatology, to pyrexia, abdominal cramping, and amoebic dysentery. Colonization of the colon results in the formation of distinct flask-shaped ulcers along the epithelium, and eventual penetration of the lamina propria via the production of matrix metalloproteinases. ALA then develops through trophozoite migration via the mesenteric hepatic portal circulation, where microabscesses coalesce to form a single, large right-lobe abscess, commonly on the posterior aspect. The progression of infection to invasive disease is contingent on the unique interplay between host and pathogen factors, such as the strength of host-immunity to overcome infection and inherent pathogenicity of the species. As a preventable illness, complications such as ALA impose a significant burden on the healthcare system. This mini-review highlights epidemiological trends, risk factors, diagnostic modalities, treatment approaches, and opportunities for prevention of -induced ALA, to help address this endemic problem on the island of SLK.
PubMed: 31992948
DOI: 10.1186/s41182-020-0193-2