Signs Of Dysplasia Research Articles

Changes in the Cellular Composition of the Rat Thymus 90 Days After Urethane Injection Against the Background of Selenium Intake

The aim of the study is to assess the cellular composition of rat thymus when isolated administration of selenium, urethane and combined exposure to two factors. Material and methods. The study was performed on 34 male Wistar rats, which were divided into 4 groups: 1 – intact, 2 – rats, which received selenium only for 1 month, 3 – animals, which were injected once intraperitoneal urethane, 4 – rats with combined selenium and urethane action. Histological preparations of the thymus were prepared according to generally accepted methods and further evaluated by the method of review microscopy, morphometry, immunohistochemical reactions, electron microscopy, statistical processing of data. Results. Ninety days after selenium, the rat thymus structure is slightly different from intact animals. The introduction of urethane leads to the development of excitation involution of the thymus, which is characterized by morphological changes, and manifests itself in a change in the shape of the organ lobes, in the expansion of the intercole gaps and in the fat tissue thereof, hyperplasia of the cortical substance of the thymus by increasing the number of mature lymphocytes, epithelial cells positive to pancytokeratin. At the ultramicroscopic level, the thymus lymphocyte decreases its nuclear-cytoplasmic index, and increases the number of mitochondria that have a light matrix with a small amount of crystal. Apoptotic bodies and a large number of electron-transparent vacuoles are visualized. When combined, the thymus structure differs from the intact group by an enlarged brain substance, but the number of epithelial cells that are positive to pancytokeratin and Ki67+-cells, as well as cells that express apoptosisregulating protein, decreases. Electron microscopy also indicates a large amount of mitochondria, but with welldefined crystals, when combined with selenium and urethane. There are a small number of electron-transparent vacuoles. Conclusion. The obtained data make it possible to draw a conclusion about the positive influence of the exchange rate of selenium on the T-cell link of immunity, at least for this period of study. In the course of the experiment, it was found that, against the background of the development of the adenoma of the lung caused by the introduction of urethane, at the stage of alveolar epithelium dysplasia signs of excitant thymus involution were detected. When selenium and urethane are combined, less pronounced changes are observed in the examined organ than in the isolated administration of urethane.

Diagnosis of Columnar Metaplasia of the Esophageal Mucosa in Patients with Complicated Gastroesophageal Reflux Disease

Aim: to improve methods of diagnostics of esophageal mucosal forms of metaplasia and dysplasia in patients with complicated forms of gastroesophageal reflux disease (GERD) using multidisciplinary approach.Material and methods. Overall, 131 patients aged 18 to 84 years (mean age — 55.8 ± 16.7 years) with confirmed diagnosis of GERD complicated by development of metaplasia of mucosa of distal esophagus were included in retroand prospective study. At the prehospital stage the patients' complaints were estimated, anamnesis was taken. At the first stage of the diagnostic program all patients underwent detailed esophagogastroduodenoscopy in high resolution with white light. The region of esophageal mucosa with signs of metaplasia and determination of its prevalence was examined and evaluated with special attention. Ultrashort segment was revealed in 26 patients, short segment — in 47 patients, long segment of mucosal metaplasia was revealed in 58 patients. Then to reveal the signs of dysplasia we used specifying endoscopic methods: the structure of pitted and microvascular pattern was estimated in narrow spectral mode using BING classification system. If an irregular type of metaplasized epithelium structure was detected in the process of BING assessment, the areas suspicious for dysplasia were marked, followed by aim forceps biopsy from them. The next stage was staining of the metaplasized segment with 1.5 % ethanic acid solution — acetowhitening. PREDICT classification system was used to evaluate the stained mucosal sections with metaplasia. Targeted forceps biopsy was performed from the altered areas that most quickly lost their coloring. The final stage of the diagnostic program in all patients was a forceps biopsy of the mucosa of the metaplasic segment according to the Seattle protocol, which requires increasing the number of fragments as the metaplasic segment lengthens in a “blind” biopsy. The biopsy material was stained with hematoxylin and eosin, and periodic acid Schiff reaction was performed in combination with alcyanine blue according to the standard technique.Results. Endoscopic examination in white light and evaluation of metaplasia extent revealed ultrashort segment (<1 cm) in 26/131 (19.9 %) patients; short segment (1–3 cm) — in 47/131 (35.9 %); long segment (> 3 cm) — in 58/131 (44.3 %) patients. Among the diagnostic techniques used, the BING and PREDICT classifications had the highest accuracy, sensitivity, and specificity (accuracy — 88.9 and 95.3 %, sensitivity — 90.5 and 91.3 %, and specificity — 86.7 and 100 %, respectively), which significantly exceeded the Seattle protocol also used in this work. The results showed a low level of specificity (31.2 %), accuracy (54.5 %), and sensitivity (76.8 %) of the Seattle protocol. The use of BING and PREDICT classifications provided marking of compromised zones, allowing targeted histological sampling.Conclusions. The original study demonstrated the greatest sensitivity, specificity, and accuracy of PREDICT and BING methods in the diagnosis of metaplasia with signs of dysplasia in patients with complicated GERD. It is also important that the use of BING and PREDICT classification systems allows to reduce the number of biopsy samples in comparison with their unreasonably large number according to the Seattle protocol, thereby reducing mucosal and submucosal trauma of the esophagus and the risk of complications.

Loss of SMARCA4 Leads to an Impaired Hematopoiesis in Mice

SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a) is the central ATPase containing enzyme in the SWI/SNF- (switch/sucrose non-fermentable) complex, which regulates chromatin accessibility and thereby influences gene transcription. By acting as a transcriptional activator or repressor in different cell types, SMARCA4 and the SWI/SNF complex have various functions. Our aim was to understand the function of SMARCA4 in healthy hematopoiesis in order to then apply our findings to different hematologic diseases in a second step. To investigate the role of SMARCA4 in haematopoiesis and hematopoietic stem cells, we created a transgenic Smarca4 knockout mouse model. An inducible knockout system was chosen since early embryonic knockout of SMARCA4, which is crucially involved in embryonic development leads to a lethal phenotype. The Cre/loxP system was used to induce homozygous Smarca4 knockout under the control of the hematopoiesis-specific promotor Mx-1. We then performed blood counts, bone marrow smears and RNA sequencing, including analysis of RNA signature of the different cell types in the bone marrow to decipher the composition of the bone marrow of Smarca 4 deficient mice. Blood count analysis showed that Smarca4 knockout mice have significantly lower leukocyte, reticulocyte, and thrombocyte counts. In addition, bone marrow showed lower colony forming capacity in colony formation assays compared to healthy cre-negative control mice. Bone marrow smears displayed aplasia of all cell lines in Smarca4 knockout mice with additional signs of dysplasia as hypolobulatedmegakaryocytes or nuclear blasts. RNA-sequencing revealed 749 upregulated and 520 downregulated genes with a log fold change ≥ +/- 1 in the bone marrow of Smarca4 knockout mice compared to cre-negative control mice. Relevant over represented pathways according to REACTOME data base included genes of generation of second messenger molecules, cell surface interactions at the vascular wall, and immunoregulatory interactions between lymphoid and non-lymphoid cells. Through cell type deconvolution (CIBERSORTx) of the bulk microarray gene expression data we estimated abundances for different cell types. Results revealed a decrease in granulocyte and macrophage progenitors (statistically significant) as well as in eosinophil progenitor cells, and in erythroid pre-colony forming units. Interestingly, both common myeloid and common lymphoid progenitors were increased. It seems as if the progenitor cells accumulate and take a different path when Smarca4 is knocked out in these cells (figure 2). We conclude that SMARCA4 is crucial for cell growth and differentiation of progenitor cells in the bone marrow during hematopoiesis since a Smarca4 knockout leads to differentiation arrest and accumulation of distinct progenitor cells and pancytopenia in peripheral blood. Figure 1: Abundances for 23 cell populations in Smarca4 knockout (KO) and wildtype (WT) samples were estimated using CIBERSORTx. Bubble plot showing Log2 fold changes of average abundances in KO vs WT with accumulation of distinct progenitor cells in the bone marrow of Smarca4 deficient mice. As underlying signature-matrix the haemopedia gene set was used. Bubbles with black borders indicate significance of difference between samples.

THU169 Role Of Growth Hormone (GH) Therapy In Short Children With Skeletal Dysplasias And Pathogenic Variants In The COL2A1 Gene

Abstract Disclosure: L.D. Cellin: None. K.G. Guimaraes: None. N.L. Menezes De Andrade: None. G.A. Vasques: None. E.D. Goiano: None. M. Akkari: None. C. Santili: None. A.A. Jorge: None. A.C. Malaquias: None. Introduction: COL2A1 is the primary collagen synthesized by chondrocytes and plays a critical structural role in regulating cell growth, differentiation, and migration. Mutations in the COL2A1 gene may cause heterogeneous phenotypes ranging from skeletal dysplasia to nonsyndromic short stature. Clinical characteristics in COL2A1-related disorders are abnormalities in the ocular, skeletal, oro-facial, and audiological systems. Unfortunately, data were scarce about GH treatment in short children with pathogenic variants in COL2A1.Objective: To evaluate recombinant growth hormone (GH) treatment in short children carrying mutations in the COL2A1 gene. Methods: Retrospectively, we selected 8 prepubertal patients with short stature and pathogenic variants in the COL2A1 gene who were treated with GH (mean dose of 45.8 ± 7.9 µg/kg/d at the start). The primary outcomes were changes in height SDS and growth velocity in the 1st year and at the end of treatment. Results: Five patients were male; 3 were disproportionate, and 5 showed skeletal dysplasia signs. Two had familial short stature. At the start of the treatment, the mean calendar age was 8.1 ± 3.9 yr, and bone age was 6.9 ± 4.2 yr. The mean height SDS was -4.0 ± 0.9 for the CDC reference. In the 1st year of therapy, the growth velocity (GV) increased from baseline values of 5.2 ± 1.9 cm/yr to 7.4 ± 1.4cm/yr, an increment of 2.2 ± 2.2cm (p=0.02). GV SDS increased from -1.2 ± 1.5 to 1.2 ± 1.8 in the whole cohort during the 1st year of treatment (p=0.02). Height SDS showed a modest improvement after one year of therapy (from -4.0 ± 0.9 to -3.5 ± 0.9; p=0.005). To improve adult height, we treated two patients with GnRH analogs associated with GH. After a mean duration of therapy of 5.5 ± 2.5 years, 5 patients ended the treatment with rhGH (one prematurely stopped therapy due to poor growth response). No increment was observed in height SDS at the end of treatment (from -3.8 ± 0.9 to -3.4 ± 1.3; p=0.2). Four patients achieved adult height after 6.4 ± 1.7 years of therapy (height SDS ranging from -3.4 ± 0.4 to -2.9 ± 0.8; p=0.08). The mean gain in adult height SDS was 0.5 ± 0.4 (ranging from zero to 0,97). Conclusions: Our patients with COL2A1-associated disorders showed no response to GH therapy to improve adult height as a group. However, we need more studies to determine which patient will benefit from this treatment once there is considerable phenotype heterogeneity. GnRH analogs may help to improve adult height in association with GH. Also, alternative therapies might be evaluated to treat short children with these disorders. Presentation: Thursday, June 15, 2023

A young patient at a neurologist’s appointment: features of diagnostics and therapy

Outpatient neurological appointments in most cases consist of patients older than 45 years. The novel coronavirus pandemic has changed this statistic. Young patients began to turn to polyclinics more often with complaints of headache, feeling of weakness, decreased physical activity, forgetfulness, and changes in concentration. COVID-1 9 provoked the development of coagulopathy in patients with genetic mutations and signs of dysplasia. The percentage of patients with acquired or congenital thrombophilia has increased. Most of them had certain manifestations of undifferentiated dysplasia, with signs of impaired venous outflow with a characteristic cephalgic syndrome. The peculiarity of which is polymorphism, inconstancy, the absence, in most cases, of connection with specific vascular and hemodynamic factors (excluding headache in venous thrombosis), a decrease in the frequency of occurrence as the disease progresses. The presence of certain complaints (headache, asthenia, cognitive impairment) requires the appointment of specific therapy. Monotherapy with one drug, even if it has a pleiotropic effect, does not always achieve therapeutic goals, since one or another mechanism of pharmacological action prevails, and the rest are secondary, requiring enhancement or other drugs, or non-drug methods. Given the poor adherence of young patients to treatment, the way out of this situation is the use of combined drugs. Combination drugs can be used as multifunctional drugs, potentiating or summarizing their effects, while reducing the risk of polypharmacy and unwanted side reactions. One of the most promising combinations is Picamilon Ginkgo (Ginkgo biloba leaf extract + Nicotinoyl gamma-a minobutyric acid), which has established itself as an effective corrector of asthenia and cognitive impairment in patients of any age.

Identifying sex-specific injury predictors as a key factor in maintaining optimal physical activity levels.

Optimal physical activity is known to reduce cardiovascular, respiratory and endocrine system diseases and, as a consequence, improve quality of life. An important risk factor for reinjuries during normal exercise is the initial connective tissue pathology. The variety of clinical dysplastic manifestations significantly complicate the timely diagnosis of this comorbidity. To establish pathognomonic sex-specific dysplasia phenotypes that indicate a particular sensitivity to physical exertion. The study involved 117 participants with recurrent musculoskeletal injuries that occurred during normal exercise. There were 67 women (57.26%) and 50 men (42.74%), which made it possible to compare the presence of the identified signs between sexes. A validated questionnaire was used to screen their connective tissue status. Ranking the most commonly revealed dysplasia signs depending on their clinical significance made it possible to establish pathognomonic sex-specific phenotypes that indicated a particular susceptibility to injuries. Individualized programs of optimal physical activity are necessary for men with chest deformities, flat-valgus feet, dolichostenomelia, arachnodactylia, hemorrhoids, abdominal muscle diastasis and recurrent hernias. In women, special sensitivity to physical exertion was associated with a combination of signs such as asthenic body, joint hypermobility, overly soft auricles, thin hyperelastic skin, atrophic striae, telangiectasias and varicose veins. Of particular importance were universal signs such as gothic palate, scoliosis, kyphosis, leg deformities, temporomandibular joint crunching, and moderate to high myopia. Participants' connective tissue condition should be considered when designing optimal physical activity programs. Identifying the established sex-specific dysplasia phenotypes will allow timely optimization of training loads, thus reducing the risk of injury.

With Phenotypic Signs of Connective Tissue Dysplasia: Cross-Sectional Clinical Study

Background. The dental health is an integral part of a person's well-being. Students of higher educational institutions comprise a health risk group, since they experience extensive physiological changes and personal socialization. The impact of connective tissue dysplasia on dental health is a relevant research task.Objective. To analyze the correlation between dental pathology and phenotypic signs of connective tissue dysplasia in first-year students.Methods. A cross-sectional clinical study of the dental health and phenotypic signs of connective tissue dysplasia was conducted as part of routine dental examination of 263 first-year students of KubSMU, aged 18–23. All participants were divided into 2 groups: group 1 – participants with 0-2 signs of connective tissue dysplasia (n = 108); group 2 – participants with 3 or more signs of dysplasia (n = 155). Statistical analysis of the results was carried out using Microsoft Excel 2010 and Statistica 6.0.Results. Unsatisfactory and poor oral hygiene levels in the group of participants with connective tissue dysplasia outnumber these levels in the control group by 30% and 22%, with very poor level in the second group 2.3 times higher (p ≤ 0.05). The incidence of noncarious tooth pathology in individuals with dysplasia is 26% higher than in the control group. The caries intensity index in group 2 is almost 20% bigger than in the control group. As expected, the group of participants with no signs of dysplasia revealed better periodontal health, namely 51.85% versus 45.81% (p ≤ 0.05). In terms of mucosal pathology, a statistical significant difference between groups 1 and 2 was noted for traumatic injuries (16.35% and 19.35%, respectively). Dentofacial abnormalities were observed more often in individuals with 3 or more phenotypic signs of connective tissue dysplasia.Conclusion. Higher morbidity rate of caries and noncarious pathology in the group of first-year students with 3 or more phenotypic signs of connective tissue dysplasia, compared to the group with 0–2 phenotypic manifestations of dysplasia, indicated the need to create a database of the dentofacial profiles of students, develop an algorithm for regular medical check-up of students, as well as provide differentiated preventive and therapeutic measures for students with dysplasia.

Severe anemia and neutrophilic leukocytosis resembling Sweet’s syndrome in a dog

Sweet’s syndrome is a rare inflammatory condition characterized by the presence of neutrophilic infiltrate of the skin. We describe a case of severe anemia and neutrophilia with post-mortem findings resembling Sweet's syndrome in a five-years-old female Labrador Retriever with bilateral epistaxis, hematemesis, hyporexia, pale oral mucosa, and fever. Laboratory analysis evidenced severe unresponsive anemia, thrombocytopenia, and leukocytosis. Biochemistry showed hypoalbuminemia and increased ALT and SAP activities. The patient was transfused and received doxycycline and prednisone for one week without improvement. Two further blood transfusions were administered. Bone marrow analysis showed a mild erythroid hypoplasia, granulocytic hyperplasia, myeloid to erythroid ratio of 6.01:1 (reference: 0.9:1 – 1.76:1) without dysplasia, mild megakaryocytic hyperplasia, and increased iron stores. Macrophages were slightly increased in number with erythrophagocytosis, and immune-mediated anemia was considered. Immunosuppressive treatment was prescribed to reduce red blood cell destruction, but no improvement after one week was observed, and euthanasia was performed. Necroscopic findings resembled those described for the systemic form of Sweet's Syndrome. Bone marrow histopathology showed remarkably increased granulopoiesis and destruction of platelets and erythrocytes. Sweet's syndrome is frequently associated with hematologic malignancy or drug exposure. Leukemia was excluded after bone marrow analysis because no increase in blast population was seen as well as no signs of dysplasia. Previous treatment could be related to the development of Sweet's syndrome, which might be the primary event. Although rare, this syndrome should be considered in the differential diagnosis of dermatosis and leukocytosis when infectious agents are not identified.

Rare case of myelodysplastic syndrome with near-tetraploidy and TP53 mutation

Introduction. Chromosomal numerical aberrations are very common in hematological malignancies, but near-tetraploidy (80?104 chromosomes) is rare in myeloid lineage malignancies, with only a few cases reported in myelodysplastic syndrome (MDS). Due to a small number of cases with this rare cytogenetic abnormality, clinicopathological significance of near-tetraploidy in MDS is still unknown. In this case report we present a case of de novo MDS patient with near-tetraploidy in association with TP53 mutation, and we aimed to elucidate the prognostic significance of this rare genetic feature. Case outline. In August of 2018, a 71-year-old male presented with severe anemia, thrombocytopenia, leucopenia, and enlarged spleen. Laboratory data were as follows: hemoglobin (Hb) 93 g/L, white blood cells 2.8 ? 109/L and platelets 23 ? 109/L. The bone marrow aspirate was hypercellular, megakaryocytes were not found, 15% of granulocytic cells were with signs of dysplasia, and 16% of blast cells without Auer rods. The finding was in correlation with diagnosis of MDS, type refractory anemia with excess blasts 2 which was also confirmed by immunophenotyping. Cytogenetic finding was near-tetraploidy (48,XY+mar[10]/92,XXYY[10]), and TP53 mutational analysis showed the presence of mutation in exon 8 (p.D281A; c.842 A > C). The patient received from time to time packed red blood cells and platelets, and died four months after initial diagnosis. Conclusion. Near-tetraploidy associated with TP53 mutation has been described in only a few MDS cases. Results of these reports including ours suggest that the association of TP53 mutation and near-tetra polyploidy is a poor prognostic factor.

Is oral lichen planus a potentially malignant disorder?: A critical appraisal; a commentary on the letter to the editor.

Is oral lichen planus a potentially malignant disorder?: A critical appraisal; a commentary on the letter to the editor.

Comparison of CEA and IgG serum levels in oral lichenoid lesions before and after treatment with topical corticosteroids.

Background. Lichen planus is considered a potentially malignant condition with an unknown etiology. This study aimed to determine the carcinoembryonic antigen (CEA) and IgG serum levels in different oral lichenoid lesions before and after treatment with local corticosteroids. Methods. Two groups of 23 individuals, including oral ulcerative lichenoid lesions patients and healthy ones, were evaluated. Toluidine blue staining and biopsy examinations were carried out while visual analog scale (VAS) was used to evaluate symptoms. By applying corticosteroids, CEA and IgG serum levels were determined before and three weeks after intervention and at the end of the study (9 weeks) with ELISA and turbidimetry methods, respectively. Results. Before the intervention, there was no significant difference in CEA serum levels between the control and case groups (P=0.19). Moreover, the CEA serum levels indicated no significant difference before and after treatment in the case group (P=0.30). While IgG serum level was significantly higher before the intervention (P=0.01), it decreased significantly in the case group after treatment (P=0.02). In addition, pain intensity reduced significantly in the case group (P=0.05). According to statistics, 8.2% out of 21.7% of patients with positive staining results exhibited dysplasia signs. Conclusion. However, neither CEA nor IgG serum levels were different in patients diagnosed with or without dysplasia and positive or negative staining results (P>0.05). IgG serum levels and pain severity effectively decreased in the oral ulcerative lichenoid lesions patients treated with local corticosteroids. Therefore, this treatment can be considered an effective and low-complication treatment modality for lichenoid lesions.

Ectodysplasin A1 Deficiency Leads to Osteopetrosis-like Changes in Bones of the Skull Associated with Diminished Osteoclastic Activity.

Pathogenic variants of the gene Eda cause X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by structural abnormalities or lack of ectodermal appendages. Signs of dysplasia are not restricted to derivatives of the ectodermal layer, but mesodermal abnormalities, such as craniofacial dysmorphism, are also frequently observed, suggesting close reciprocal interactions between the ectoderm and mesoderm; however, a causal link has remained unsubstantiated. We investigated the functional impact of defective ectodysplasin A1 (Eda1) signaling on postnatal bone homeostasis in Eda1-deficient Tabby mice. Interestingly, Eda1 was detected in wild-type mouse calvariae throughout postnatal lifetime. In calvariae, bone-lining Osterix (Osx)+ osteoblasts stained positive for Eda1, and osteoclasts were revealed as Eda receptor (Edar)-positive. Moreover, adult Eda1-deficient calvarial bone showed osteopetrosis-like changes with significantly diminished marrow space, which was maintained during adulthood. Concomitantly with osteopetrosis-like changes, Tabby calvarial bone and Tabby bone marrow-derived osteoclasts had far less osteoclastic activity-associated co-enzymes including cathepsin K, Mmp9, Trap, and Tcirg1 (V-type proton ATPase a3 subunit) compared with wild-type calvariae in vivo or osteoclasts in vitro, indicating that Eda1 deficiency may affect the activity of osteoclasts. Finally, we confirmed that nuclear Nfatc1-positive osteoclasts were strongly diminished during mature osteoclastic differentiation under M-CSF and RANKL in the Tabby model, while Fc-EDA treatment of Tabby-derived osteoclasts significantly increased nuclear translocation of Nfatc1. Furthermore, we identified enhanced Nfatc1 and NF-κB transcriptional activity following Fc-EDA treatment in vitro using luciferase assays. Overall, the results indicate that diminished expressions of osteoclastic activity-associated co-enzymes may lead to disturbed bone homeostasis in Tabby calvariae postnatally.

S1987 Cap Polyposis: A Rare Condition in a Pediatric Patient Successfully Treated With Endoscopic Treatment

Introduction: Cap polyposis is a rare condition of the rectum or sigmoid colon manifested by inflammatory polyps covered by a thick layer of fibrinopurulent mucus. This condition typically presents as mucoid diarrhea and rectal bleeding, and patients are often prescribed antibiotics (such as those for Helicobacter pylori), steroids, infliximab, or aminosalicylates. Surgical management is an option for unresponsive disease, but endoscopic management has been rarely reported. Case Description/Methods: A 16-year-old boy had a 10-year history of mucoid diarrhea and occasional rectal bleeding and incontinence. Previous endoscopy revealed pseudopolyps in the rectum that appeared inflammatory with granulation tissue. Initial laboratory evaluation revealed mild iron deficiency, anemia, and hypoalbuminemia. The patient was treated with limited polypectomy, topical steroids, and diphenoxylate-atropine, which did not resolve his symptoms. A full workup for inflammatory bowel disease with an upper endoscopy, colonoscopy, and magnetic resonance enterography showed indications of marked polyposis in the rectum that was suggestive of “cap polyposis”. Tests for H. pylori were negative. There was no improvement with metronidazole or with treatments to reduce straining during bowel movements. Repeat sigmoidoscopy showed diffuse 1–4-cm multilobulated polypoid lesions in the rectum. Initially ESD was considered but deemed unsuitable due to poor lifting of the lesions. Thus, wide field endoscopic mucosal resection (WEMR) was performed, Approximately 40 band ligations with snare endoscopic submucosal resection were performed with near complete removal of all of the lesions. There was no post-procedure bleeding, pain, or other adverse effects. The resected tissue specimen had signs of high-grade dysplasia away from the resection margins. The patient’s symptoms resolved, and a second-look procedure 3.5 months later revealed only a slightly nodular area with no signs of dysplasia or cap polyposis. Discussion: Patients with cap polyposis typically report mucoid stools and rectal bleeding, and evaluations reveal a characteristic pattern on colonoscopy and pathology. For cases of cap polyposis in which conservative medical management fails, wide-field endoscopic mucosal resection is a viable option.

S3497 Tubulo-Villous Adenoma of the Distal Ileum Presenting With Small Bowel Obstruction-Like Symptoms

Introduction: Small bowel tumors (SBT) are rare and account for < 3% of all gastrointestinal tumors in the United States. Given their insidious presentation with non-specific symptoms, they can evade detection and cause delays in diagnosis. Case Description/Methods: A 74-year-old lady came to the ER with abdominal pain, nausea, vomiting and abdominal distention since two days. Past medical history included esophageal spasm, GERD, achalasia, hypertension, CKD with anemia and fibromyalgia and had undergone total abdominal hysterectomy. At her last colonoscopy 10 years ago a 5 cm tubular adenoma was excised and a repeat was advised after 5 years, which she did not follow up with. EGD 8 years ago showed grade 1 reflux esophagitis, normal stomach and small bowel. Pulse was 100/minute and BP was 132/77. Abdomen was soft and distended, with tenderness in the right upper quadrant and epigastrium. Hb was 9.2 g/dL, consistent with her baseline. Though abdominal CT suggested SBO with a transition point just proximal to the ileocecal valve, a small bowel series ruled out an SBO. The patient was made NPO and NGT was placed. Colonoscopy revealed a partially obstructing, medium-sized, fungating, friable, infiltrative, circumferential, villous mass, 8-10 cm away from the ileocecal valve. Histopathology confirmed tubulovillous (TV) adenoma with no signs of dysplasia or malignancy. The patient underwent robotic-assisted ileocecectomy and recovered well. Follow up colonoscopy 4 months later showed healing ileocolonic anastomosis, with no stricture or ulceration. (Figure) Discussion: Though the small bowel constitutes 90% of the surface area of the GI tract, it contributes to < 2% of GI malignancies. Reasons for this include the more liquid contents causing less mucosal irritation than solid colonic contents and rapid transit. Adenomatous polyps, the most common benign SBTs, have an epithelial origin. Histological types include tubular, villous and tubulovillous. Villous components, atypia or large size increase the risk for malignancy. Presenting symptoms are nonspecific and they are commonly found unexpectedly during surgery in patients with SBO. Evaluation in symptomatic patients includes endoscopy with biopsies. Push, double-balloon, or video capsule endoscopy may be needed. Diagnostic laparoscopy or surgical exploration can help establish a definitive diagnosis. Given their potential for malignant transformation, TV adenomas must be removed, and patients should be monitored for recurrence.Figure 1.: A: XR small bowel with oral contrast suggestive of mucosal irregularity with narrowing around distal ileum. B: Colonoscopy showing partially obstructing, circumferential villous mass, 8-10 cm from the ileocecal valve. C: Histo-pathology showing epithelial finger-like projections away from the muscularis mucosae, lined by dysplastic epithelium.

ALENTUZUMAB AS THIRD LINE TREATMENT IN PURE RED SERIE APLASIA - A SUCCESSFUL CASE REPORT

Pure red cell aplasia (PRCA) is a rare hematologic disorder characterized by reticulocytopenic, normocytic anemia with absence of red cell precursors in bone marrow, normal granulopoiesis, and megakaryopoiesis. The disease may be associated with viral infections, large granular lymphocytic leukemia, chronic lymphocytic leukemia, or thymoma, but the most common form is idiopathic. Refractory PRCA may respond to more profound immunosuppression with anti-CD52. To describe a refractory PRCA patient treated with anti-CD52 humanized monoclonal antibody, alemtuzumab, with good response. A 52-year-old male patient with hemophilia A, previously treated with cryoprecipitate and currently using prophylactic Factor VIII, presents to healthcare with severe asthenia, no bleeding episodes during the period. Laboratory evaluation: Hb 3.4 g/dL; Ht 10.6% VCM 95; WBC 6.490 × 10 9 /L; Platelets 196 × 10 9 /L, intense reticulocytopenia (25 × 10 9 /L). He had normal renal function, liver function, LDH, vitamin B12, folic acid, iron profile; serology with positive anti-HCV. Bone marrow evaluation showed 50-60% cellularity with intense hypoplasia of the erythroid series, granulocytic series with no changes in morphology or maturation pattern, and normal megakaryocytes with no signs of dysplasia. After investigation with immunoglobulin dosing, chest CT, flow cytometry for LGL, and serology for parvovirus, all normal, the diagnosis of constitutional APSV was confirmed. Treatment with cyclosporine (CSA) at a dose of 6mg/kg was initiated, with no reticulocyte response. In addition, he evolved with progressively increasing bilirubin levels (BT 7.4 BD 5.6) concomitant with a significant increase in Hepatitis C viral load (380,667 IU/mL Log: 5.58). Immunosuppression was discontinued, treatment with sofosbuvir and simeprevir was initiated, with good viral response. However, he required red blood cell transfusions every 2-3 weeks; new therapy was restarted with CSA and prednisone. The patient did not tolerate this treatment and developed severe thrombocytopenia and no improvement in hemoglobin levels. Considering the high risk of bleeding, CSA was discontinued. Platelet count normalized but he continued to require mensal RBC transfusion. At this point, second-line therapy with IV Alentuzumab, 3 mg dose followed by 6 weekly 15 mg doses (total 96 mg), coupled with infectious prophylaxis, has been proposed. Response occurred as early as the third infusion, as documented by a rapid increase in reticulocyte count. Within seven weeks the patient had a complete response (Hb 12.4 g/dL, Vg 35.3% and reticulocytes 170 × 10 9 /L). He had no toxicity-related intercurrences and remained with a complete response after six months of treatment. Unfortunately, a further progressive drop in hemoglobin after nine months from the end of the first treatment was observed. We opted to restart Alentuzumab at a dose of 15 mg/month, and follow with this maintenance dose. After the third application, the patient again showed a complete response (Hb 14.3 g/dL and VG 40.5%). Currently, the patient continues to use the medication every 45 days with a maintained hemoglobin level. Small case series cite Alentuzumab for refractory APSV as a treatment possibility with 63% overall response. We suggest use in refractory cases, followed by maintenance dosing to avoid relapse in long-term follow-up.

S1780 Immunoglobulin G4-Associated Cholangitis Mimicking Cholangiocarcinoma in Elderly

Introduction: Sclerosing cholangitis is a diffuse inflammation and fibrosis that progressively leads to stenosis and destruction of the bile ducts. It includes 3 types: primary sclerosing cholangitis (PSC), secondary cholangitis, and IgG4 sclerosing cholangitis (IgG4-SC). Usually they all present with cholestatic symptoms like pruritus and abdominal pain along with elevated ALP and GGT as well as bilirubin, however IgG4-SC has better outcomes, treatment response to steroids and less recurrence. We hereby presenting a case of IgG4-SC presenting as cholangiocarcinoma. Case Description/Methods: An 80 year-old male with a past medical history of bladder cancer was referred to the gastroenterology for EUS after blood work showed (ALT 320, AST 297, Bilirubin 1.4, GGT 2032), and CT abdomen with IV contrast revealed intra and extrahepatic biliary dilatation with an abrupt cutoff in mid CBD, suspicious for either a primary CBD mass or pancreatic mass (Figure). EUS showed an irregular mass in the CBD wall, suspicious for cholangiocarcinoma (Figure). The ERCP showed malignant appearing stricture of the extrahepatic bile duct consistent with cholangiocarcinoma, Bismuth 2 vs early 3B (Figure). Exploratory laparotomy was done and portal node biopsy came back benign; for which a repeat ERCP/Spyglass with direct visualization cholangioscopy, was done and showed diffusely dilated main bile duct with sludge and pus, single diffuse stenosis in right hepatic duct sludge with lining malignant appearing abnormal mucosa (nodularity and dilated vessels). IgG4 was elevated (931) consistent with IgG4 cholangitis (Figure). Biopsy and cytology brush showed no signs of dysplasia or neoplasia. Patient was then started on prednisone for a month and scheduled to repeat ERCP/Spyglass after. Discussion: IgG4-RD is a fibrous-inflammatory process related to immunomodulation, therefore IgG4-SC often co-presents with auto-immune pancreatitis, dacryoadenitis and sialadenitis. IgG4-SC is extremely challenging, as it’s frequently misdiagnosed on imaging as a pseudotumor, and can progress to liver cirrhosis if left untreated, however it comes with great response to steroids. In 2021, Mendoza criteria (tortuous vessels, irregular nodulations, raised intraductal lesions, irregular surface, and friability) was published and found to be accurate to differentiate malignant and benign causes of biliary stricture, with overall diagnostic accuracy of 77%. Our case didn’t meet the 5 criterias of Mendoza, which is consistent with IgG4-SC.Figure 1.: Top: CT of abdomen and ERCP. Bottom: Exploratory laparotomy.

Use of DNA image cytometry in conducting oral cancer screening in rural India

Oral cancer screening can assist in the early detection of oral potentially malignant lesions (OPMLs) and prevention of oral cancers. It can be challenging for clinicians to differentiate OPMLs from benign conditions. Adjunct screening tools such as fluorescence visualisation (FV) and DNA image cytometry (DNA-ICM) have shown success in identifying OPMLs in high-risk clinics. For the first time we aimed to assess these technologies in Indian rural settings and evaluate if these tools helped clinicians identify high-risk lesions during screening. Dental students and residents screened participants in five screening camps held in villages outside of Hyderabad, India, using extraoral, intraoral, and FV examinations. Lesion and normal tissue brushings were collected for DNA-ICM analysis and cytology. Of the 1116 participants screened, 184 lesions were observed in 152 participants. Based on white light examination (WLE), 45 lesions were recommended for biopsy. Thirty-five were completed on site; 25 (71%) were diagnosed with low-grade dysplasias (17 mild, 8 moderate) and the remaining 10 showed no signs of dysplasia. FV loss was noted in all but one dysplastic lesion and showed a sensitivity of 96% and specificity of 17%. Cytology combined with DNA-ICM had a sensitivity of 64% and specificity of 86% in detecting dysplasia. DNA-ICM combined with cytology identified the majority of dysplastic lesions and identified additional lesions, which were not considered high-risk during WLE and biopsy on site. Efforts to follow-up with these participants are ongoing. FV identified most high-risk lesions but added limited value over WLE.

Results of cytological examination of bone marrow aspirates in patients with HIV infection and cytopenia in correlation with viral load

Aim determination of specific changes in the bone marrow in patients with HIV infection and cytopenia, depending on the viral load.&#x0D; Material and methods. We analysed myelograms of patients with HIV infection and cytopenia. All patients had bicytopenia or pancytopenia in the hemogram.&#x0D; Results. In patients with a viral load over 100 001 copies/ml, the hypocellularity of each of the hematopoietic cell line was significantly more often observed, hypercellularity was recorded only in the myelograms of patients with a viral load of less than 100 001 copies/ml. When assessing the signs of myelodysplasia in the bone marrow, changes in the megakaryocyte lineage (the formation of naked cells, dysmegakaryocytopoiesis) were typical for patients with a viral load of less than 10 000 copies/ml. Signs of dysplasia of the granulocytic lineage are more often determined in patients with a viral load of more than 100 001 copies/ml.

Особливості перебігу артеріальної гіпертензії, поєднаної з дисплазією сполучної тканини, у практиці сімейного лікаря

Актуальність. Поєднання артеріальної гіпертензії (АГ) та дисплазії сполучної тканини (ДСТ) є одним із недостатньо вивчених питань. ДСТ супроводжується порушеннями структури та функції судин, сприяє розвитку раннього атеросклерозу та серцево-судинних ускладнень. У хворих на АГ, поєднану з ДСТ, часто зустрічаються порушення ритму та провідності серця, значно поширені зміни з боку органів зору, внутрішніх органів та кістково-суглобової системи. Мета. Покращити діагностику та лікування АГ, поєднаної з ДСТ, на основі вивчення клінічного перебігу, вираженості зовнішніх і внутрішніх симптомів ДСТ, ліпідного спектра крові, гострофазових показників, сечової кислоти та інструментальних методів обстеження. Матеріали та методи. Проведено клінічне дослідження, в яке включено 75 хворих на АГ ІІ стадії 1–3-го ступеня з проявами ДСТ, середній вік яких становив 63,5 ± 4,2 року, які перебували на стаціонарному лікуванні в кардіологічному відділенні Комунальної міської клінічної лікарні швидкої медичної допомоги м. Львова. Методи дослідження включали клінічні (огляд, пальпація, перкусія, аускультація), лабораторні (ліпідний спектр крові, С-реактивний протеїн, серомукоїди та сечова кислота), інструментальні (електрокардіографія, ехокардіографія, добове моніторування артеріального тиску, езофагогастродуоденоскопія, ультразвукове дослідження (УЗД) внутрішніх органів і судин нижніх кінцівок, УЗ-дуплексне обстеження сонних і хребтових артерій, рентгенологічне дослідження кістково-суглобової системи), консультації офтальмолога, невропатолога, травматолога, стоматолога. Діагностика недиференційованої ДСТ визначалася за методикою Т.М. Кадуріної та співавт. (2009). Розрахунок діагностичного коефіцієнта для кожної ознаки дисплазії проводили за методикою, розробленою В.М. Яковлевим та співавт. (2008). Пацієнти були розподілені на 3 групи:1-ша група — 12 пацієнтів з АГ II стадії 1-го ступеня, 2-га група — 26 пацієнтів з АГ II стадії 2-го ступеня, 3-тя група — 30 пацієнтів з АГ II стадії 3-го ступеня. Контрольна група — 7 пацієнтів з АГ ІІ стадії 1–3-го ступеня без проявів ДСТ. Результати. При порівняльному аналізі хворих з АГ у 90,67 % спостерігався ряд зовнішніх і внутрішніх симптомів дисплазії сполучної тканини, у 9,33 % були відсутні прояви ДСТ. У 3-й групі хворих спостерігали більше зовнішніх і внутрішніх фенотипових ознак ДСТ та їх вираженість порівняно з 1-ю та 2-ю групами, що прогнозує тяжкість клінічного перебігу захворювання. Висновки. У хворих на АГ спостерігається значне поширення ДСТ: чим більше ознак ДСТ, тим тяжчий клінічний перебіг гіпертонії. У хворих з АГ, поєднаною з ДСТ, поширені зміни з боку серцево-судинної системи, органів зору, внутрішніх органів та кістково-суглобової системи порівняно з групою хворих без ДСТ. При порівнянні групи хворих з АГ і наявністю ДСТ відмічаються вищі показники активності запального процесу та ліпідного спектра крові, ніж у хворих без ДСТ. Своєчасне виявлення АГ, поєднаної з ДСТ, систематичний диспансерний нагляд за хворими, проведення комплексу заходів, спрямованих на покращення структури та функції сполучної тканини, корекція імунодефіциту дозволяють покращити результати перебігу даної патології.

ГЕНЕТИЧЕСКИЕ ОСНОВЫ РАЗВИТИЯ ДИСПЛАЗИЙ СОЕДИНИТЕЛЬНЫХ ТКАНЕЙ И РАСПРОСТРАНЁННОСТЬ ИХ ФЕНОТИПИЧЕСКИХ ПРИЗНАКОВ СРЕДИ ЧЛЕНОВ СБОРНЫХ КОМАНД РОССИИ

Phenotypic signs of connective tissue dysplasia are widely represented among the population. It is believed that the incidence of dysplasia among athletes is much higher than in the population, since changes in connective tissues lead to the formation of special anthropometric characteristics and predisposition to certain physical qualities, for example, fl exibility. However, the role of the genes responsible for the development of non-syndromic connective tissue dysplasia remains unclear. Also debatable is the question of the relationship between the presence of phenotypic signs of dysplasia and the development of complications from the cardiovascular system that occur under the infl uence of intense physical activity.