Chronic Inflammatory Infiltrate Research Articles

DESI-MSI-guided exploration of metabolic-phenotypic relationships reveals a correlation between PI 38:3 and proliferating cells in clear cell renal cell carcinoma via single-section co-registration of multimodal imaging.

A workflow has been evaluated that utilizes a single tissue section to obtain spatially co-registered, molecular, and phenotypical information suitable for AI-enabled image analysis. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to obtain molecular information followed by conventional histological staining and immunolabelling. The impact of varying DESI-MSI conditions (e.g., heated transfer line (HTL) temperature, scan rate, acquisition time) on the detection of small molecules and lipids as well as on tissue integrity crucial for integration into typical clinical pathology workflows was assessed in human kidney. Increasing the heated transfer line temperature from 150 to 450°C resulted in a 1.8-fold enhancement in lipid signal at a scan rate of 10 scans/s, while preserving histological features. Moreover, increasing the acquisition speed to 30 scans/s yielded superior lipid signal when compared to 10 scans/s at 150°C. Tissue morphology and protein epitopes remained intact allowing full histological assessment and further multiplex phenotyping by immunofluorescence (mIF) and immunohistochemistry (mIHC) of the same section. The successful integration of the workflow incorporating DESI-MSI, H&E, and immunolabelling on a single tissue section revealed an accumulation of ascorbic acid in regions of focal chronic inflammatory cell infiltrate within non-cancerous kidney tissue. Additionally, a strong positive correlation between PI 38:3 and proliferating cells was observed in clear cell renal cell carcinoma (ccRCC) showing the utility of this approach in uncovering molecular associations in disease pathology.

Urinary liver-type fatty acid-binding protein level as a prognostic indicator of acute kidney injury secondary to severe falciparum malaria.

Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria.

Ameloblastic Carcinoma in a Young Adult Male Patient - A Case Report

ABSTRACT Ameloblastic carcinoma is a rare malignant odontogenic tumor that is further classified into being primary or secondary arising from a preexisting benign ameloblastoma. It affects the mandible in two thirds of the patients. There is no standard treatment protocol for this lesion but radicalsurgical excision with or without radiotherapy is reported in the majority of cases. In this paper, we present a case of a 22 year old male diagnosed with Ameloblastic carcinoma of the mandible with a clinical course of typical aggressiveness and extensive destruction. Histopathological examination of the incised biopsy showed a parakeratinized stratified squamous epithelium with underlying fibrous connective tissue stroma. The stroma is highly myxomatous and exhibits islands of odontogenic epithelium and chronic inflammatory cell infiltrates. Interlacing strands of odontogenic epithelium shows stellate reticulum-like cells and occasional areas of squamous metaplasia with cellular and nuclear pleomorphism. In addition, mitotic figures were noted. With the correlation of clinical, radiographic, and histological features, the lesion is diagnosed as ameloblastic carcinoma. The lesion was surgical excised and post-treatment follow-up for 6 months revealed no recurrence of the malignancy.

Hepatobiliary Ascariasis in a Piglet

PurposeAscariasis caused by the helminth Ascaris suum is the most common parasitosis of swine worldwide and it may involve all age categories of pigs. The present study reports an unusual localization of A.suum worms in the biliary system of a piglet slaughtered for human consumption.MethodsThe liver was subjected to ultrasound scan and pathological examination. The isolated worms were morphologically examined and the DNA was extracted for the molecular identification of the species involved.ResultsA total of 43 preadult nematodes were found within the gallbladder and the bile ducts. Parasites were morphologically identified as belonging to the genus Ascaris and molecularly as A. suum. At gross examination, the liver was moderately enlarged, with the bile ducts severely dilated. A chronic inflammatory infiltrate was noted, often centered around ectatic bile ducts (up to 5 mm in diameter), lined by hyperplastic epithelium and filled with sections of nematodes. The worm sections showed smooth cuticle, coelomyarian musculature, and an intestinal tract lined by columnar, uninucleated cells within a pseudocoelom. The ex vivo ultrasonographic examination of the liver allowed the visualization of several nematodes in the bile duct lumen and could be suggested for in vivo diagnosis. Unfortunately, the absence of the intestine did not allow to define the pathogenesis of the infection.ConclusionAlthough, given the unusual nature of this finding, it is difficult to identify predisposing factors for this A. suum localization, it suggests that ascariasis should be considered in the differential diagnosis of pigs with hepatobiliary disease.

Helicobacter pylori Increasing Spread of An Inflammation Cells and Gastric Mucosal Atrophy in Gastritis Patients

Background Helicobacter pylori (H. pylori) is a bacterium which could reason chronic gastritis and then has the capability to purpose gastric mucosal atrophy. The modifications within the degree of gastric mucosal atrophy have been appreciably correlated with the degree of risk of gastric cancer. The purpose of the observe turned into to research the relationship among H. pylori and the spread of inflammatory cellular infiltration and gastric mucosal atrophy in gastritis patients in Banjarmasin. Method The study was carried out in September-November 2021 using a cross-sectional method with purposive sampling, that is as many as 87 samples of histopathological slides of gastritis patients in the anatomical pathology laboratory of Sari Mulia Hospital, Banjarmasin for the period 2019. Research analysis used Kolmogorov-Smirnov. Slide preparations were stained with immunohistochemistry (IHC) and hematoxylin-eosin (HE). Inflammatory cellular clearance was measured the use of a scale from revised Sydney system and gastric mucosal atrophy become measured the use of the OLGA staging system. Results The results showed as many as 40 (45.98%) H.pylori-positive patients with the most chronic inflammatory cell infiltration in 24 (60%) patients at grade 3 (p<0.001) and for gastric mucosal atrophy as many as 29 (72, 50%) of patients at various stages (p<0.001). Conclusion H. pylori has a significant relationship with inflammatory cell infiltration and gastric mucosal atrophy. H. pylori-positive causes a growth within the severity of inflammatory cellular irritation and mucosal atrophy in gastritis patients.

Evaluation of calcium hydroxide mixed with propolis by ultrasonic activation as root canal dressing in delayed tooth replantation.

In cases of tooth avulsion, in which the neurovascular bundle responsible for nourishing the dental pulp is break, endodontic treatment is necessary before proceeding with tooth replantation. In this process, various substances have been tested in combination with calcium hydroxide Ca(OH)2 in an attempt to improve its effectiveness. This study aimed to examine the effects of using a mixture of Ca(OH)2 and 10% propolis, with subsequent application of ultrasonic treatment, on the delayed replantation of teeth in rats. Twenty-four rats underwent a surgical procedure to extract the upper right incisor, leaving it on a surface to dry for one hour. The pulp and periodontal ligament were removed and the teeth were submerged in a 2% sodium fluoride acidulated phosphate solution. The canals were dehydrated using paper cones and the teeth were divided into four groups, according to the type of intracanal dressing: Ca(OH)2 group, Ca(OH)2 group with ultrasonic agitation, Ca(OH)2 and propolis group, Ca(OH)2 and propolis group with ultrasonic agitation. The root canals were irrigated with saline solution and the teeth were reimplanted. Sixty days after reimplantation, the animals were euthanized. With regard to the presence of acute and chronic inflammatory infiltrate in the periodontal ligament, there was no statistically significant difference among some of the groups. Root resorption was identified in all groups, and there was no significant difference between them. It is concluded that the application of intracanal dressing containing Ca(OH)2 associated with 10% propolis, followed by ultrasonic agitation, did not prove to be more effective than the use of Ca(OH)2 alone in the repair process in the delayed replantation of rat teeth. Key words:Tooth replantation, Calcium hydroxide, Propolis, Ultrasound, Intracanal dressing.

Case of Ray Fungus Presenting with Abdominal Distension

Actinomycosis is a rare infection caused by filamentous, non acid fast staining and gram positive bacteria. The diagnosis is rarely made preoperatively, and only histopathological examination can confirm it, as the condition presents with varied clinical manifestations, often resembling a malignant lesion on radiographic images. Hereby, the authors present a case of a 67-year-old female, who was admitted for evaluation of an abdominal mass. Radiologically, the mass resembled a desmoplastic fibroma, and clinically, it was suspected to be the same. The mass was excised and sent for histopathological examination. Grossly, two specimens were received. The first consisted of adherent bowel loops, including the ileum, appendix, caecum and descending colon, with the mass arising from mesentery involving the bowel, measuring 11.5x9.5x6 cm. The second specimen was a partial cystectomy specimen, with the abdominal wall mass infiltrating the bladder anteroposteriorly, measuring 11x10x8 cm. Microscopic examination revealed extensive areas of inflammation with actinomycotic organisms exhibiting the Splendore-Hoeppli phenomenon, along with numerous multinucleated giant cells and acute on chronic inflammatory infiltrate. Surrounding areas showed dense collagen bundles. The prognosis after complete surgical resection is good, along with the administration of broad spectrum intravenous antibiotics.

Compositional and surface changes of retrieved stainless-steel hardware and its effects on surrounding soft tissues: A prospective study.

To evaluate the surface, compositional, and histological changes in the overlying soft tissues of retrieved stainless-steel mini-plates and screws used for rigid internal fixation in the maxillofacial skeleton. A prospective study was conducted comprising 60 patients who sustained maxillofacial trauma and underwent ORIF in our unit previously and who required hardware retrieval in the post-operative phase. The retrieved hardware was evaluated for surface and compositional changes with the help of a scanning electron microscope for surface roughness and corrosion changes. Energy-dispersive X-ray study was done to know the composition and metal release from the hardware. The data obtained from these results were compared with a control unused and a sterile stainless-steel mini-plate and screw. The effects of the corrosion changes of this hardware on the adjacent soft tissues were evaluated histologically to assess the cellular changes of the soft tissue cover overlying the stainless-steel mini-plates and screws. A total of 96 stainless-steel mini-plates and 380 stainless-steel screws were retrieved from 60 patients. The control plate was smooth without any surface and corrosion defects, while the retrieved mini-plates irrespective of the reason for removal have shown surface roughness. Fe and Ni ions were found to be significantly reduced in the retrieved mini-plates. The presence of CrC in the retrieved plates indicates corrosion, which was seen only in hardware retrieved from symptomatic patients. The histological study revealed chronic inflammatory cell infiltrate with hyalinized connective tissue in all the samples irrespective of the reason for the removal of the plate. Stainless-steel mini-plates and screws act as a potent foreign body material and initiate a localized inflammatory reaction due to its corrosive products with longer duration of stay. Hence, the authors advocate the overall shift in the use of stainless-steel hardware to titanium hardware for ORIF.

Xanthogranulomatous Osteomyelitis: Two Rare Cases Report

INTRODUCTION: Xanthogranulomatous osteomyelitis (XO) is a rare chronic inflammatory lesion that is histologically characterized by the presence of foamy histiocytes and plasma cells (1-8). Radiologic and gross examinations can mimic malignancy (9), so carful workup and definitive diagnosis should be made by histopathologic evaluation. Case Report: There are two rare cases being reported here; the first one is a 21-year-old male who presented with chronic pain and swelling of upper leg for one year. He has history of healed traumatic fracture of fibula 7 years ago. Radiological examination revealed highly suspicious radio opaque lesions of upper fibula. The second case is a 30 years old female, presented with pain and swelling of wrist for six months with clinical suspicion of Ewing sarcoma. Radiological examination revealed highly suspicious radio opaque, lytic lesions of lower radius. Biopsy of both lesions were done. Microscopic examination showed marked chronic inflammatory cells infiltration mainly foamy histiocytes and lymphoid cells with many foreign body giant cells. No evidence of tuberculosis or malignancy. Conclusion: As these lesions were clinically highly suspicious of malignancy or associated with other diseases, so proper diagnostic roles in xanthogranulomatous osteomyelitis should include histopathological examination in order to rule out any malignant conditions of the bone.

Congenital Pulmonary Airway Malformation Type 1 with Pulmonary Neuroendocrine Cell Hyperplasia in an Adult Male: a Rare Case Report

Abstract Introduction/Objective Congenital pulmonary airway malformations (CPAM) is rare, usually diagnosed in the pediatric population, and may occur in adults. Pulmonary neuroendocrine cell hyperplasia (PNECH) mimicking diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) associated with CPAM has not been described previously. We report a case of CPAM Type 1 with PNECH. Methods/Case Report A 33-year-old male, with past medical history of latent tuberculosis (TB) by Quantiferon blood testing, recurrent pneumonia, recurrent lung abscesses, and lung cavitary lesion for three years, presented with fever, cough with hemoptysis, shortness of breath, and left-sided chest pain. Computerized tomography of chest displayed a 10.8 cm cavitary lesion in the left lower lobe of the lung. The patient underwent left lower lobectomy of the lung. Grossly, the lobectomy specimen revealed a 10.5 cm irregular cavity communicating to the superior segmental bronchus of the left lower lobe. Microscopically, the dominant large cyst was surrounded by lung parenchyma and small cystically dilated spaces resembling bronchioles under the fibrotic pleura. The large cyst was lined by respiratory epithelium with rare pathognomonic mucous cells in clusters. Cyst walls contained smooth muscle, small islands of cartilage, and focal intense acute and chronic inflammatory cell infiltrates with hemorrhage. There were multiple foci of proliferation of pulmonary neuroendocrine cells centered around bronchioles surrounding the large cyst. The neuroendocrine cells were arranged from individual cells and cellular aggregates to larger tumorlets, highlighted by Synaptophysin and Chromogranin immunostains. No granuloma or necrosis was present. No acid-fast bacilli or fungal microorganisms were identified by special stains. The findings are consistent with CPAM type 1, with PNECH. Results (if a Case Study enter NA) NA Conclusion Our study demonstrates a histologically diagnosed adult congenital pulmonary airway malformations type 1 with an incidental pulmonary neuroendocrine cell hyperplasia, which mimics diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. To the best of our knowledge, this is the first report of such an association.

Nasal Gouty Tophus

A 48-year-old, non-hypertensive, non diabetic man with uncontrolled gouty arthritis presented with a four-day swollen nasal mass. He was assessed to have a nasal abscess at the emergency room and was admitted for urgent management. Paranasal computed tomography (CT) scans showed a heterogeneously enhancing focus with areas of hypodensities in the nasal apex and dorsum extending into the right ala measuring 1.5 x 2.8 x 3.4 cm. with associated erosion of the cartilaginous part of the anterior nasal septum, soft tissue swelling and skin thickening in the nasal dorsum, nasal tip and right zygomatic region that was suspected to relate to an aggressive etiology. Tissue correlation was therefore recommended, and he underwent endoscopic-guided incision and drainage with biopsy and debridement of the nasal mass. The specimen submitted consisted of red to white, irregular, soft tissue fragments with an aggregate measurement of 1.5 x 1.5 x 0.5 cm. Microsections showed deposits of amorphous white to pink material with surrounding fibrosis and acute and chronic inflammatory cell infiltrates and foreign body giant cells. (Figures 1 and 2) Also seen in the background were fragments of sclerotic bone and bacterial colonies. These findings were consistent with gouty tophus with acute and chronic inflammation and bacterial colonization. The culture and sensitivity test of the nasal discharge showed growth of Enterobacter aerogenes (currently named Klebsiella aerogenes) which was identified by an automated mass spectrometry microbial identification system (VITEK® MS). Work-up also included uric acid levels which were within the reference interval at that time (6.57 mg/dL).

A CRITICAL REVIEW ON KAPHAJ YONIVYAPADA W.S.R CHRONIC CERVICITIS

In Ayurvedic classics, almost all gynecological disorders come under the big heading of Yonivyapada. This also includes menstrual disorders, abortions or stillbirths and diseases of uterus, cervix and vagina. Chronic cervicitis is judged by the presence of a heavy mixed chronic inflammatory cell infiltrate. This condition causes congestion and fibrosis of cervix and is characterized by mucopurulent vaginal discharge with foul smelling, pruritus vulvae, dyspareunia, failure of conception etc. The disease chronic cervicitis can be put parallel to kaphaj yoni vyapada on the basis of signs and symptoms. Here an attempt has been made to correlate chronic cervicitis with kaphaj yoni vyapada describes in Ayurvedic classics.

Morphologic alterations in the mucosa of the denture site in patients with full removable dentures from acrylic plastics

Relevance. Currently, many new agents have appeared on the market for users of removable dentures to improve adhesion, i.e. fixation and stabilization of dentures. It is important to evaluate the effect of such agents on the denture bed mucosa.Objective. Morphological substantiation of the effectiveness of the use of adhesive cream for fixation of prostheses Asepta Рarodontalu patients with removable dentures made of acrylic plastic.Materials and methods. The study involved 49 patients (12 men and 37 women) of elderly age (62–75 years) who suffered complete loss of teeth on both jaws. All patients were divided into 3 study groups: 1 (control) group, who had previously refused to have full removable acrylic dentures made for them; 2 (comparison) group, patients to whom removable acrylic dentures were made and who did not use any means to improvetheir fixation; 3 (main) group, patients to whom full removable acrylic dentures were made and who during the adaptation period and subsequently for a year used a domestic adhesive cream for fixation; 3 (main) group, patients to whom full removable acrylic dentures were made. In order to solve the realization of the set goal of the study, a number of clinical and histological studies with the use of immunohistochemical method were carried out, outpatient charts of dental patients were analyzed.Results. It was found that dystrophic and chronic inflammatory changes in the soft tissues of the denture bed were most pronounced in the case of using dentures without means to improve their fixation. At use of domestic adhesive cream for fixation of dentures Asepta Рarodontal the process of keratinization of the oral mucous membrane epithelium was minimal, there was no fibrosis of the own lamina of the mucous membrane, scattered infiltration was less expressed than in people not using acrylic dentures or using them without adhesive means, and was represented at the expense of lymphocytes, single neutrophilic granulocytes on the background of single leukostases. The immunohistochemical study showed that T-lymphocytes and mast cells were predominant in the preparations of group 2 patients, and they appeared in the preparations of this group of patients comparatively more than in the 1st control and 3rd main groups of the study, which confirmed the presence of the most pronounced chronic inflammatory infiltration in group 2 patients.Conclusion. The most optimal condition of the denture bed mucosa was observed in patients who used removable acrylic dentures for a year and simultaneously applied an adhesive agent for their fixation (domestic adhesive cream for denture fixation Asepta Рarodontal). It is obviously connected with the protection of the mucous membrane of the prosthetic bed by the adhesive cream from the mechanical impact of a dense acrylic plastic prosthesis, as well as with the reduction of contact with food products aggressive in temperature and structure.

Cytological changes in respiratory epithelium in association with marijuana smoking

Marijuana is one of the commonly used illicit drugs in Nigeria. This study evaluated the cytological changes in the respiratory epithelium associated with marijuana smoking in Calabar Municipality, Cross River State, Nigeria. This study was a cross- sectional study involving 100 marijuana smokers and 50 marijuana non-smokers, aged 15 years and above. Sputum samples were aseptically collected, and smears prepared. The smears were fixed in ethyl alcohol and were stained using Giemsa and Papanicolaou staining techniques. The stained smears were examined using x10 and x40 objectives of light microscope. Photomicrographs of stained smears were obtained. Data were represented in percentages in tables. Chi-square was used to determine statistical difference between two categorical variables. P-values < 0.05 were considered significant. Marital status, level of education and age of subjects significantly influenced the smoking of marijuana (p=0.001). There was a significant increase in the number of marijuana smokers between the age of 15 – 24(p=0.001) when compared with other age groups. There were also significant abnormalities (p=0.001) observed in the respiratory epithelium of marijuana smokers when compared with non-marijuana smokers. Respiratory cytology smears from marijuana smokers who have smoked for at least 10 years showed mild to moderate metaplasia, numerous acute and chronic inflammatory infiltrates while those who have smoked for more than 10 years showed giant epithelial cells, multinucleated cells and clumps of dysplastic cells. Data from this study showed that marijuana smoking causes inflammatory and dysplastic changes in the respiratory epithelium.

Concept «grade-stage» in morphological diagnostics of chronic colitis in inflammatory bowel disease

Purpose: to propose a new approach in the morphological diagnosis of colitis using the categories grade and stage to clarify and decipher the diagnosis of chronic colitis and improve the quality of biopsy diagnostics.Materials and methods. The study included 100 cases of inflammatory bowel disease (IBD) diagnosed between 2017 and 2021 (70 cases of ulcerative colitis and 30 cases of Crohn's disease). The age of the patients ranged from 19 to 53 years. In all cases, the diagnosis was established on the basis of a complex of clinical, laboratory and instrumental diagnostic methods. Multiple biopsies were obtained in all patients during colonoscopy. The processing of the biopsy material was carried out according to the generally accepted method. To evaluate plasma cells, an IHC study with antibodies to CD138 (syndecan-1) (Dako RTU) was additionally performed.Results. In the course of the study, a gradation of morphological criteria was carried out, which are decisive in the diagnosis of chronic colitis in patients with IBD. The concept of chronic colitis as a process characterized by the grade of severity and stage of chronic inflammation has been revised and re-formulated. Criteria of structural disorders (stage of colitis from 0 to 3) and criteria of severity of chronic inflammatory infiltrate (grade of colitis from 0 to 3) were identified and graded. Additionally, an attempt was made to objectify the selected criteria using an IHC study using antibodies to CD138 plasma cells (syndecan-1). Based on the material of colonobiopsies, the proposed degree-stage approach was tested in the group of colitis in patients with IBD, which showed the possibility of its practical application.Conclusion. The proposed concept will be able to improve the quality of biopsy diagnostics and avoid unjustified use of the term "chronic colitis" without further elaboration and, accordingly, its frequent unjustified use existing at the moment.

A case-control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S-100 and toluidine blue stain and its therapeutic implications.

The pathogenesis of prurigo nodularis (PN) is considered to be multifactorial, with numerous cells and cytokines confabulating to produce an aberrant immune response. A cross-sectional observational study was done in cases of untreated primary prurigo nodularis cases with histopathological assessment in 49 cases from lesional and nonlesional skin with assessment of epidermal and dermal changes, dermal infiltrate, S-100 andtoluidine blue staining to assess the expression of nerve and mast cells. The most common histological changes seen in lesional skin were hyperkeratosis (98%), irregular hyperplasia (69.4%), hypergranulosis (69.4%), subepidermal clefting (6%), vertical collagen bundles (51.0%), and dermal fibrosis (48.9%). Chronic inflammatory infiltrate was seen in all cases (100%) predominantly of lymphocytes (100%) followed by eosinophils (18.4%), plasma cells (8.2%), and neutrophils (2.0%). There was a marked increase in the expression of S-100 (6.92 ± 3.40 vs. 3.94 ± 2.15, P < 0.001) and toluidine blue (4.99 ± 4.47 vs. 1.22 ± 1.28, P < 0.001) in the lesional skin as compared to the nonlesional skin. We can infer that the epidermal and dermal pathology in PN is related to the infiltrate of lymphocytes, mast cells, and neural hyperplasia which perpetuate the pathogenesis by triggering the itch-inflammation cycle. Thus, apart from immunosuppressive agents that target lymphocytes and their cytokines, therapy targeted at mast cells and neural proliferation may be needed to treat prurigo nodularis.

Common Diagnostic Challenges and Pitfalls in Segmental Colitis Associated with Diverticulosis (SCAD).

Segmental colitis associated with diverticulosis (SCAD) is characterized by inflammation involving the sigmoid inter-diverticular mucosa, sparing the proximal colon and rectum. Due to the heterogeneity of clinical manifestations and endoscopic and histological findings, SCAD diagnosis might be challenging in clinical practice. This narrative review aimed to report the SCAD diagnostic criteria adopted in different studies, highlighting the current challenges and main pitfalls in its diagnosis. We analysed fourteen studies, mainly prospective observational studies. Haematochezia and rectal bleeding were the main complaints leading to diagnosis, followed by diarrhoea. An accurate endoscopic description was performed in 86% of studies, while a standardised biopsy sampling protocol (sigma, proximal colon and rectum) was scarcely adopted, being complete only in 28.5% of studies. The evaluation of concomitant drugs potentially inducing colitis was carried out in only 57% of studies. Great heterogeneity in sigmoid endoscopic (edema, erythema, erosions, ulcers, mucosal friability) and histological findings (chronic and/or acute inflammatory infiltrate) was observed. We showed that SCAD diagnosis is often based on not fully adequate macroscopic colonic description and scant biopsy protocol sampling. An accurate clinical and endoscopic evaluation, with an adequate sampling biopsy protocol, with attention to differential diagnosis, seemed to be crucial for a prompt SCAD diagnosis.

Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner

Hepatosteatosis is characterized by abnormal accumulation of triglycerides (TG), leading to prolonged and chronic inflammatory infiltration. To date, there is still a lack of effective and economical therapies for hepatosteatosis. Oridonin (ORI) is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens. In this paper, we showed that ORI exerted significant protective effects against hepatic steatosis, inflammation and fibrosis, which was dependent on LXRα signaling. It is reported that LXRα regulated lipid homeostasis between triglyceride (TG) and phosphatidylethanolamine (PE) by promoting ATGL and EPT1 expression. Therefore, we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner, and the results showed the TG reduction and PE elevation. In detail, hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes, respectively. Taken together, the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

Otosclerosis under the magnifying glass.

Otosclerosis is a bone condition affecting the stapes bone within the otic capsule, and its exact cause is still unknown. It is characterized by a lack of proper remodeling of newly formed vascular and woven bone, leading to the development of abnormal osteons and the formation of sclerotic bone. Bilateral otosclerosis is seen in 80% of patients and 60% of otosclerosis patients have a family history of the condition. The etiology of this disease is still unknown, there are lots of theories to explain it. The histopathological (HP) studies of otosclerosis showed that osteoblasts, osteoclasts, vascular proliferation, fibroblasts, and histiocytes were observed in the stapes footplate. The onset of the symptoms occurs by the early third decade of life, usually it doesn't start later. In otosclerosis, the energy exerted by sound at the level of the tympanic membrane is reduced in the inner ear due to the fixation and rigidity of the ossicular chain, leading to hearing loss, especially for low frequencies. The primary clinical symptom of otosclerosis is conductive hearing loss but it is important to note that sensorineural hearing loss and mixed hearing loss can also occur as secondary symptoms of the condition. Another symptom present in patients with otosclerosis is tinnitus. The paper carried out a retrospective study of 70 patients diagnosed with otosclerosis in the Department of Otorhinolaryngology of Emergency City Hospital, Timişoara, Romania, between January 2021 to December 2022. Tissue fragments were processed at Service of Pathology by standard Hematoxylin-Eosin staining. The HP diagnosis was completed using Masson's trichrome staining, Giemsa histochemical staining, and immunohistochemical (IHC) reactions with anti-cluster of differentiation (CD)20, anti-CD3, anti-CD4, anti-CD8, anti-CD34, and anti-CD31 antibodies. The microscopic examination showed a chronic diffuse inflammatory infiltrate that consisted predominantly of mature T-lymphocytes, immunohistochemically positive for CD3, CD4 and CD8. There were also present rare CD20-positive B-lymphocytes. Among the lymphocytes, relatively numerous mast cells were identified, highlighted histochemically by the Giemsa staining. They had numerous purple-violet intracytoplasmic granules. In the connective tissue support, a relatively rich vascular network was identified, consisting of hyperemic capillaries, highlighted immunohistochemically with anti-CD31 and anti-CD34 antibodies. Bone tissues trabeculae showed extensive areas of fibrosis. The collagen fibers were highlighted by Masson's trichrome staining, being stained in green, blue, or bluish green.

BI26 Treatment-induced scleroderma in a patient with metastatic melanoma

Abstract We present a 71-year-old woman who presented with sclerodermoid plaques affecting the abdomen and lower limbs, following a single cycle of nivolumab and ipilimumab 20 months prior for BRAF-mutant metastatic melanoma (pulmonary and hepatic metastases). Immunotherapy was discontinued owing to iatrogenic colitis, confirmed on flexible sigmoidoscopy, and requiring oral prednisolone, infliximab and, later, modified-release beclomethasone dipropionate. Owing to the progression of hepatic disease, she was commenced on targeted therapy with dabrafenib and trametinib. A lesional punch biopsy was performed; histological analysis demonstrated a dense dermis with mild chronic inflammatory infiltrate, in keeping with a diagnosis of scleroderma. Treatment with a combination of topical corticosteroids and vitamin D analogues improved disease from 15% body surface area (BSA) to 3% after 4 months. We performed a literature search in PubMed for articles on immunotherapy-related scleroderma published up to August 2022 and identified 18 articles that met our inclusion criteria. Scleroderma was reported in patients with melanoma, non-small-cell lung cancer, renal cell carcinoma, rectal adenocarcinoma, adenocarcinoma of the lung and large-cell neuroendocrine lung cancer treated with pembrolizumab, nivolumab, atezolizumab and ipilimumab. Latency of onset ranged from 0 to 18 months, and treatment included topical and systemic corticosteroids, mycophenolate mofetil, hydroxychloroquine, cyclophosphamide, infliximab and immunoglobulins, with varying treatment outcomes. There was no clear relationship between cancer subtype, duration of treatment and response to treatment. Furthermore, the lack of documented quantitative or semiquantitative measurements for improvement such as BSA and modified Rodnan skin score is limiting. Our case report is important in promoting the awareness of localized scleroderma as a rare side-effect of immunotherapy and highlights the various treatment options available.