Mild Lymphocytic Infiltration Research Articles

Candida causes recurrent vulvovaginal candidiasis by forming morphologically disparate biofilms on the human vaginal epithelium

BackgroundRecurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC. MethodsVaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida-specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated. ResultsCandida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole. ConclusionsIn summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence.

P14 A rare adverse event of eosinophilic fasciitis secondary to immune checkpoint inhibitor therapy

P14 A rare adverse event of eosinophilic fasciitis secondary to immune checkpoint inhibitor therapy

Histological findings of thyroid cancer after lenvatinib therapy.

Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in-vivo changes in patients who underwent thyroidectomy after lenvatinib therapy. We screened 167 patients with thyroid cancer [papillary thyroid cancer (PTC), n = 102; follicular thyroid cancer (FTC), n = 26; anaplastic thyroid cancer (ATC), n = 39] who underwent lenvatinib therapy. Among these patients, six underwent thyroidectomy (lenvatinib-treated group: PTC, n = 3; FTC, n = 1; ATC, n = 2), and the specimens were examined. Five patients with PTC who did not receive lenvatinib therapy were included for comparison (untreated group). Microvessel density (MVD) was evaluated in both groups. The PTC and FTC specimens showed relatively more ischaemic changes than ATC specimens. Coagulative necrosis and ischaemic changes in cancer cells were frequently observed. ATC specimens showed fibrosis and mild cell damage. As hypothyroidism is a common side effect of lenvatinib therapy, non-cancerous thyroid tissues were also examined. Histological findings included mild lymphocytic infiltration, lymphoid follicular formation, histiocytic reaction and follicular epithelial destruction. The MVD in lenvatinib-treated tissues was significantly lower than that in untreated tissues. Lenvatinib therapy probably induces relatively specific ischaemic changes in thyroid cancer cells. Moreover, inflammatory cell infiltration and decreased MVD occur to varying degrees in non-cancerous thyroid tissue and may be related to hypothyroidism, a side effect of lenvatinib.

Large acrochordon of labium majora: an unusual location

Background: Acrochordon is a soft, round or oval, pedunculated papilloma that can be tan or brown in color. Although acrochordons most commonly appear in the neck, axilla, and groin, they can also appear in unusual sites, such as penis, vulva, and perineum. Most of the lesions are small pedunculated papules or nodules approximately 2–6 mm, but rarely, particularly on the lower section of the trunk, large pedunculated acrochordons can be found. Here we present a large acrochordon on the labium majora.
 Case Description: A 25 years old woman came to an outpatient clinic because there was a mass on her right labium majora ever since she gave birth three years prior. The size of the mass started off relatively small but has grown significantly over time. From dermatological examination in external genitalia region, there was a solitary, pedunculated, skin-colored mass measuring 10 × 3 cm, attached to right labium majora. There was no redness, ulceration, bleeding or discharge. Cautery excision with local anesthetic was performed to removed the mass. The histopathological examination of the specimen revealed polypoidal tissue lined by epidermal layer, there are proliferation and dilation of capillaries containing erythrocytes in the dermis layer, mild infiltration of lymphocytes and histiocytes. No evidence of malignancy.
 Conclusion: We report an unusual location of acrochordon presenting with large size. Due to its atypical presentation, it may be confused with a malignancy, necessitating a pathological test. Total excision of the mass is recommended.

Classic Kaposi Sarcoma: An Unusual Presentation in an HIV-Negative Man

Kaposi sarcoma (KS) is a type of cancer that develops in blood vessels of the mouth, lymph nodes, and lungs. Our case report is about a 66-year-old man with purple patches and plaques, as well as nodules distributed in the legs and arms. Biopsy of the skin lesions showed angiomatous proliferation of small vessels with mild perivascular lymphocytic infiltration with plasma cells. We started chemotherapy for this disseminated form of Kaposi sarcoma.

#4488 OLD BIOPSY IS ALWAYS GOLD, REVISING MEMBRANOPROLIFERATIVE GN DIAGNOSIS IN A RENAL TRANSPLANT PATIENT

Abstract Background and Aims MPGN resulting from hepatitis C virus (HCV) infection typically shows granular deposition of immunoglobulin M (IgM), C3, and both kappa and lambda light chains. Immunoglobulin G (IgG) may or may not be present, and C1q is typically negative, the same pathology can be found in other viral infections. The recurrence rate post-transplantation is high, with 33% of immune-complex MPGN. Graft loss is even higher 65%, especially among patients with idiopathic MPGN. Treatment of a patient with significant proteinuria can be tricky, as no proven treatment is described yet, but plasmapheresis and induction with cyclophosphamide were described for heavy proteinuria >3.5 g/day. Method 79 year old female patient, known case of live unrelated renal transplantation in December 2013, primary renal disease is unknown. She had a history of equivocal hepatitis C virus antibodies, but Hepatitis C virus RNA was not detected. She is also known to have Type II Diabetes Mellitus and hypertension. The patient had baseline creatinine of 100-120 micromol/L. 24 hr urine protein was 0.8 g/Day but started rising quickly to reach a peak of 9.2 g/g seven months post-transplantation to nephrotic range proteinuria but her serum albumin level was always above 35 g/L. Serum protein electrophoresis showed no M band, a kappa/ Lambda ratio 1.21 within a normal range (0.260-1.65). Anti- nuclear antibody (ANA), P-ANCA, C-ANCA, and Double-stranded DNA all were negative. Complements were within normal range C3 1.39 g/L (0.79 -1.52), C4 0.44 g/L(0.17-0.57)m rheumatoid factor and Anti- citrullinated peptide antibodies were negative. Hepatitis b Virus surface antigen and core antibodies were not reactive, HIV screening was negative. Urine analysis showed RBCs but no RBC casts. Renal biopsy showed mild mesangial expansion and mild l increase in mesangial cells and matrix. Some glomeruli show increased lobulation with increase in mesangial cells and matrix with segmental endocapillary proliferation There is double contour of the glomerular basement membrane with scattered spikes and holes within the basement membrane seen best with silver stain. There is mild increase in the thickness of glomerular basement membrane. There is focal mild lymphocytic infiltration. Tubulitis is not seen in the examined material. One Focal area of mild interstitial fibrosis. Sampled blood vessels are unremarkable. The stain for C4d is negative. Immunofluorescence showed granular capillary wall immunoreactivity to IgM (+2), C4 (+1), C1q (+1), and Lambda light chain (+2). The glomeruli show no immunoreactivity to IgG, IgA, C3, Kappa and fibrin. The glomeruli show (+) staining for albumin. Tubular protein reabsorption droplets showed immunoreactivity for albumin, IgG, IgM, C3, kappa and lambda light chains. Electron microscopy showed many subendothelial, and mesangial electron-dense deposits. The patient was on maintenance immunosuppression medications inform of mycophenolic acid 720 mg, cyclosporine; 250mg BID, and Prednisolone 5 mg daily.Revisiting the new classification of membranoproliferative glomerulonephritis is challenging in this patient, since there is the dominance of IgM deposition by immunofluorescence and C4 but not C3 makes it challenging, the negative monoclonal band in serum electrophoresis and negative autoimmune workup excludes immune complex mediate MPGN, leave idiopathic MPGN a possibility, keeping in mind that hepatitis C virus infection was never confirmed. On the other hand, IF showed IgM with C4 subendothelial and mesangial dense deposits that excludes away the C4 glomerulopathy. Results Whether this is a recurrence of glomerular disease early on post-transplantation or denovo membranoproliferative disease, she responded well to the addition of losartan 100 mg daily, with a reduction of her urinary protein to less than 1 g/g. the patient never received treatment for the hepatitis C virus. Conclusion In our patient, it is difficult to conclude if the cause of MPGN is recurrence or denovo GN, especially with severe proteinuria that responded well to ACEi treatment. The pathological findings can be tricky.

Nailfold Videocapillaroscopic Alterations as Markers of Microangiopathy in COVID-19 Patients.

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, United States. All COVID-19 patients studied with videocapillaroscopy showed alterations rarely seen in healthy individuals consistent with microangiopathy, such as hemosiderin deposits (sign of microthrombosis and microhemorrhages) and enlarged loops (sign of endotheliopathy). The number of hemosiderin deposits correlated both with ferritin and CRP levels (r = 0.67, p = 0.008 for both) and the number of enlarged loops significantly correlated with the levels of VWF (r = 0.67, p = 0.006). Ferritin levels were higher in non-O groups, determined by the rs657152 C > A cluster, (median 619, min-max 551-3266 mg/dL) than in the O group (373, 44-581 mg/dL, p = 0.006). Nailfold histology revealed microvascular damage, i.e., mild perivascular lymphocyte and macrophage infiltration and microvascular ectasia in the dermal vessels of all cases, and microthrombi within vessels in five cases. Alterations in nailfold videocapillaroscopy and elevated biomarkers of endothelial perturbation that match histopathologic findings open new perspectives in the possibility of non-invasively demonstrating microangiopathy in COVID-19.

Cytotoxicity, biocompatibility and osteoinductive profile of an MTA-hydrogel-based cement: An in vitro and animal study.

This study aimed to evaluate the cytotoxicity, biocompatibility and osteoinductive profile of a mineral trioxide aggregate (MTA)-hydrogel-based material (MTA Flow) in comparison with MTA Angelus. Cell viability was evaluated in human periodontal ligament stem cells (hPDLSCs) using the methyl-thiazol-tetrazolium (MTT) colourimetric assay. Polyethylene tubes containing the tested materials and empty polyethylene tubes (control) were implanted in the subcutaneous tissue of Wistar rats. Cellular (lymphocyte infiltration) and extracellular events (ECM; collagen fibres) were analysed in histological sections. Immunohistochemical (collagen I, osteopontin, bone sialoprotein, bone morphogenetic protein4) analyses were also performed. At 24, 48 and 72 h, all tested groups showed cell viability similar to control (p > .05). Regarding biocompatibility, all groups showed similar cellular events represented by a slight inflammatory reaction characterized by hyperaemia and a mild lymphocytic inflammatory infiltrate. The analysis of lymphocytes during the time showed a decrease in these cells in the control group and a significant interaction between MTA Angelus and control (p < .001), with MTA Angelus showing a more extensive inflammatory infiltrate. Regarding fibres, an increase in content was observed in all groups during the experimental time (7, 30 and 60 days), however, no difference was detected among the experimental groups (p = .063). After 60 days, the immunoexpression of bone matrix proteins in the MTA Flow group was similar to or higher than that observed in the MTA Angelus and in the control group. MTA Flow showed a non-cytotoxic behaviour, biocompatibility and ability to stimulate tissue mineralization.

T-cell Lymphoma in the Nasal Cavity in Goat

Background: Lymphomas are considered uncommon in goats, being the multicentric form with the highest number of cases for the species. Primary intranasal lymphomas are often diagnosed in dogs, cats, and humans. In the literature, there is only a description of a multicentric case involving the frontal sinuses and mucosa of the nasal cavity in a goat; therefore, it is important to describe unusual cases of this disease for the inclusion of new clinical and pathological characteristics in the ruminant clinic medicine. The objective of this work is to describe a case of T-cell lymphoma in the nasal cavity of a young goat.Case: The animal had dyspnea and respiratory noise for 15 days. Clinical examination showed nodulation in the right nasal cavity associated with serosanguinous secretion. Tracheostomy was performed; however, after 30 days the animal was euthanized. A sagittal plane of the head showed a pinkish-gray mass in the right and left nasal cavity, with a smooth, multilobulated surface, smooth adhering to the rostral portion of the dorsal concha and occluding the dorsal nasal meatus. Submandibular lymph nodes were slightly enlarged. Histopathological examination of the nasal cavity revealed a non-encapsulated, poorly delimited and ulcerated tumor composed of round cells arranged in a mantle supported by a discrete fibrovascular stroma extending the mucosa and lamina propria. Cells were round with sparse, eosinophilic and poorly delimited cytoplasm. Nuclei varied from round to elongated with condensed chromatin and evident nucleoli. Occasionally, aberrant nuclei, reniform shape and multinucleated cells were seen. Pleomorphism was moderate characterized by anisocytosis and anisocariosis. Typical and atypical mitosis were frequent (0-4 per field of highest magnification [400x]). Amidst the neoplasm, there were multifocal areas of necrosis and hemorrhage associated with a mild lymphocytic inflammatory infiltrate. Immunohistochemistry showed positive immunostaining for Vimentin antibodies and CD3, and negative for pan CK and CD20.Discussion: The lymphomas immunophenotyping is little used when it comes to farm animals, and there are few studies that use this technique for the definitive diagnosis of these neoplasms for small ruminants. The use of this technique must be considered in each case, in order to determine the pathogenesis, the accurate diagnosis and the origin of the neoplastic lymphocytes. In goats, T-cell lymphomas are the most diagnosed, although cases of multicentric B-cell lymphomas with ocular involvement have been diagnosed. In view of the clinical picture of the case described, infectious rhinitis already described in goats, such as aspergillosis and protothecosis, should be included as differential diagnoses. However, the anatomopathological findings facilitate the direction of the diagnosis, since infectious rhinitis presents as nodules / ulcerated masses or focal areas of necrosis associated with purulent secretion and in the histopathological examination it is possible to observe the intralesional etiological agents. In addition, the enzootic ethmoidal tumor must be included, as it has similar clinical signs and affects young animals, but they are adenomas/adenocarcinomas that affect the ethmoidal nasal shells induced by a retrovirus. Lymphomas in the caprine species are rare in the Northeastern semi-arid, but that in the present diagnostic routine occasionally occurs, being important the first description of its nasal shape for its inclusion in the differential diagnoses of diseases that present with clinical obstruction and dyspnea for the species. Keywords: hematopoietic neoplasia, immunophenotyping, lymphocytes, dyspnea.Descritores: neoplasia hematopoietica, imunofenotipagem, linfócitos, dispneia.Título: Linfoma de células T na cavidade nasal de caprino.

A292 ACUTE PANCREATITIS AS THE FIRST PRESENTATION OF GRANULOMATOSIS WITH POLYANGIITIS (GPA): A CASE REPORT

Abstract Background Granulomatosis with Polyangiitis (GPA) is a rare necrotizing ANCA-associated vasculitis characterized by inflammation in small-sized arteries. GPA often presents with a triad of a) upper (nasal obstruction, sinusitis, crusting rhinitis) and lower respiratory tract (lung nodules, alveolar hemorrhage) b) systemic vasculitis and c) kidney involvement (necrotizing glomerulonephritis). However, gastrointestinal involvement is exceedingly rare and only occurs in about 5-11% of GPA cases. Specifically, recurrent acute pancreatitis is even more uncommon. Purpose To raise awareness about systemic vasculitides in cases of idiopathic acute pancreatitis Method A 48-year-old female was seen in an outpatient gastroenterology clinic for recurrent idiopathic pancreatitis. She reported a six-month history of intermittent sharp epigastric pain associated with a rise in lipase. The patient noted having episodes of acute sinusitis shortly prior to the onset of her epigastric pain. Her initial labwork revealed normal creatinine and liver enzymes, elevated total bilirubin 24, lipase 316 and mildly high CRP 16.1 and ESR 27 which normalized on repeat blood work. Abdominal US was unremarkable with no gallstones, intra- or extrahepatic duct dilatation. An abdominal MRI revealed segmental enlargement of the distal tail/body of the pancreas consistent with resolving focal pancreatitis. A follow-up MRI 5 weeks later revealed progression of pancreatic swelling and intermittent narrowing of the pancreatic duct. These findings were suspicious for an inflammatory process such as autoimmune pancreatitis. The patient then underwent EUS-guided examination and FNA of her pancreas. Pathology revealed focal chronic pancreatitis with fibrosis and mild lymphocytic infiltrate, but was not suggestive of autoimmune pancreatitis. She was then treated empirically with a 3-month course of prednisone and had significant improvement in her symptoms and interval resolution of pancreatic inflammation on repeat MRI. After discontinuation of her steroids, her symptoms recurred with intermittent epigastric pain, facial pain and sinusitis. She was then seen by rheumatology and an autoimmune panel was ordered. Result(s) Autoimmune work-up revelead positive anti-PR3 (27 RU/ml), negative anti-MPO and normal IgG-4 levels. Ultimately a diagnosis of limited GPA, which spares the kidneys, was made given the patient’s clinical presentation and positive anti-PR3 antibody. Since there was no life-threatening organ involvement, she was elected to start methotrexate therapy and had significant improvement in her symptoms. The plan is to stay on methotrexate for at least 24 months and have regular follow-up to ensure clinical stability. Conclusion(s) Acute pancreatitis is a rare initial presentation of GPA vasculitis. It is important to consider autoimmune disease and systemic vasculitides in cases of idiopathic pancreatitis after ruling out common causes. Early diagnosis and therapy allow for high rates of remission and improved survival rates. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

In Graves’ disease, thyroid autoantibodies and ultrasound features correlate with distinctive histological features

PurposeLaboratory, imaging, and pathological features of Graves’ disease (GD), although well characterized, have been barely correlated each other. Aim of the study was to link laboratory and ultrasound characteristics of GD with its pathological features.MethodsWe correlated laboratory and ultrasound data at the time of diagnosis in 28 consecutive GD patients who underwent thyroidectomy with their pathological features, i.e., lymphocytic infiltration and follicular hyperplasia (both classified as mild or severe).ResultsThyroid volume correlated positively with the levels of FT4 (P = 0.002, r2 = 0.42), FT3 (P = 0.011, r2 = 0.22), autoantibodies to thyroglobulin (TgAbs) (P = 0.016, r2 = 0.32), autoantibodies to thyroid peroxidase (TPOAbs) (P = 0.011, r2 = 0.34) and the extent of lymphocytic infiltration (P = 0.006 comparing mild to severe lymphocytic infiltration) but not with the levels of autoantibodies to the thyrotropin receptor (TRAbs) and to follicular hyperplasia. Compared to subjects with mild lymphocytic infiltration, those with severe lymphocytic infiltration showed higher levels of TgAbs (316 vs 0.0 IU/mL, P < 0.0001) and TPOAbs (295 IU/mL vs 14 IU/mL, P < 0.0001) and similar levels of TRAbs (7.5 vs 13 IU/mL, P = 0.68). Compared to patients with mild, those with severe follicular hyperplasia had similar levels of TgAbs (76 vs 30 IU/mL, P = 0.31) and TPOAbs (251 IU/mL vs 45 IU/mL, P = 0.26) but higher levels of TRAbs (39 vs 7.2 IU/mL, P < 0.001).ConclusionIn GD, TgAbs and TPOAbs levels correlate with the extent of lymphocytic infiltration, TRAbs levels with the degree of follicular hyperplasia. Thyroid volume, the main factor influencing the severity of hyperthyroidism, is related to lymphocytic infiltration and not to follicular hyperplasia.

Variants in the Gene Encoding Filaggrin Cause Autosomal-Dominant Symmetrical Acral Keratoderma

Variants in the Gene Encoding Filaggrin Cause Autosomal-Dominant Symmetrical Acral Keratoderma

Cecal Reduction of Brachyspira and Lesion Severity in Laying Hens Supplemented with Fermented Defatted ‘Alperujo’

Antimicrobial resistance demands the development of therapeutic alternatives such as prebiotics, probiotics, and nutraceuticals. The aim of this study was to assess the antimicrobial proprieties of the nutraceutical fermented defatted “alperujo”, derived from olive oil production, in a laying hen farm (n = 122,250) endemic with avian intestinal spirochetosis (Brachyspira spp.). Part of the batch (n = 1440) was divided into six groups of 240 hens each that included 80 or 108-week-old laying hens, supplemented with 0%, 2%, or 6% fermented defatted ‘alperujo’ for a month. At the end of the experiment, eight hens from each group were autopsied and cecal content was subjected to (i) Brachyspira culture and species identification by PCRs, and (ii) direct DNA extraction and Brachyspira qPCR. Furthermore, the ceca were processed for histopathology. Microbiological isolation revealed B. pilosicoli and B. hyodysenteriae co-infection in all groups. The 80-week-old hen group 2% supplemented showed a reduction in the cecal Brachyspira content (qPCR) compared with non-supplemented hens. Cecal histopathology showed a diffuse mild infiltration of lymphocytes, plasma cells, and heterophils; and hyperplasia of the gut-associated lymphoid tissue hyperplasia which decreased in severity in 80-week-old supplemented hens. The reduction in Brachyspira colonization and the severity of the lesions observed in supplemented hens highlights a potential protective function against avian intestinal spirochetosis.

S3315 Acute Cholestatic Hepatitis Following m-RNABNT162b2 SARS-CoV-2 Vaccination: Could It Be Genetic?

Introduction: Given the morbidity and mortality of COVID-19, development of vaccines targeting SARs-CoV-2 was essential. Despite their overall safety and efficacy, atypical complications have been reported. We report a case of post-vaccination acute cholestatic hepatitis, consistent with drug-induced liver injury (DILI). Case Description/Methods: A 61-year-old man with no past medical history presented with 2 weeks of jaundice and pruritus, 1 month after his second dose of the m-RNABNT162b2 SARS-CoV-2 vaccine. He denied use of any medications, supplements, tobacco, alcohol, drugs, or family history of liver disease. Vital signs and physical exam were unremarkable. Admission labs included ALP 265 U/L, AST 50 U/L, ALT 68 U/L, total bilirubin 14.9 mg/dL, and direct bilirubin 12 mg/dL. Ultrasound revealed normal liver surface without ductal dilatation, confirmed by MRCP. Serologies (HIV, HAV IgM, HBV core IgM, HBV surface antigen, HCV antibody), autoimmune markers (ANA, anti-mitochondrial, anti-actin, anti-liver-kidney-microsomal), and respiratory viral panel (SARS-CoV-2, influenza A/B, RSV) were negative. Hemoglobin, platelets, INR, albumin, gamma-glutamyl transpeptidase (GGT), and immunoglobulins were normal. Percutaneous liver biopsy revealed cholestasis with mild portal lymphocytic infiltrates and lobular inflammation (Figure 1), without portal fibrosis, PAS+ globules, or iron deposition. Molecular genetic testing (Next Generation Sequencing, Prevention Genetics® 77 Gene Cholestasis Panel) was performed. No genetic variants were identified in 77 genes associated with cholestasis, though single copy variants of several autosomal recessive genes were detected. Symptoms resolved with supportive care. Labs one month later were notable for ALP 175 U/L, (AST hemolyzed), ALT 68 U/L, and total bilirubin 3.2 mg/dL. Discussion: Prior reports have described cholestasis due to immune-mediated hepatitis after COVID mRNA vaccination1, but these features were absent in this case. Given the patient’s normal GGT, we hypothesized that increased cytokine release led to cholestatic injury in an individual genetically predisposed to cholestasis by genetic variation in ATP8B1 or ABCB11. Future studies comparing genetic variants in patients with liver injury may provide insight into mechanisms of idiosyncratic DILI following mRNA vaccination against SARS-CoV-2.Figure 1.: Liver biopsy showing cholestasis in a patient who developed jaundice after COVID mRNA vaccination.

Nitazoxanide, Ivermectin, and Artemether effects against cryptosporidiosis in diabetic mice: parasitological, histopathological, and chemical studies.

Human cryptosporidiosis is one of the most significant causes of water borne epidemics of diarrhea worldwide. It is extremely important in immunocompromised hosts and malnourished children as it could cause severe life-threatening diarrhea. Despite the global burden of the disease, there are only few available therapies against cryptosporidiosis. Diabetes mellitus is a common metabolic disorder that impair both the innate and adaptive immune responses of the patient. This study aimed to test the effect of Nitazoxanide, Ivermectin, and Artemether against cryptosporidiosis in diabetic mice. Sixty white albino mice were categorized into 6 groups; 10 mice each: GI: normal non-infected non-treated (healthy- control), GII-GVI (diabetic groups), GII: non-infected non treated (diabetic control), GIII: infected non treated (infected control), GIV: infected and treated with Nitazoxanide (NTZ), GV: infected and treated with Ivermectin (IVC), GVI: infected and treated with Artemether (ART). Parasitological, histopathological, and chemical examinations were done to evaluate the effect of NTZ, IVC, and ART against cryptosporidiosis in diabetic mice. Parasitological examination revealed maximum reduction of oocyst shedding in GVI, while histopathological examination showed the least pathologic changes in GV with mild vascular wall fibrosis and moderate lymphocytic infiltration of islets of Langerhans. Measurement of blood glucose level showed the best results with GIV. Nitazoxanide is effective against cryptosporidiosis in diabetic patients with minimal hyperglycemia, Artemether is especially effective in reducing the oocyst shedding in stool, whereas Ivermectin is associated with the least pathological changes in pancreatic islets of Langerhans.Graphical abstract

Effect of fish meal substitution with dried bovine hemoglobin on the growth, blood hematology, antioxidant activity and related genes expression, and tissue histoarchitecture of Nile tilapia (Oreochromis niloticus)

Our study was designed to highlight the efficacy of fish meal (FM) replacement with dried bovine hemoglobin (DBH) on the Oreochromis niloticus (O. niloticus) growth, health antioxidant activity, and antioxidant-related gene expression for 70 days. Fish (n = 225, average weight: 36.37 ± 0.05 g) were fed diets with different replacement percentage of FM with DBH: 0 % (DBH0), 2.5 % (DBH2.5), 5 % (DBH5), 7.5 % (DBH7.5) and 10 % (DBH10), where DBH0 was kept as control diet. At the end of the feeding trial, the fish were exposed to bacterial challenge with the pathogenic bacteria Aeromonas veronii (A. veronii). Compared to the DBH0 group, there was a notable increase in the growth parameters with a lower feed conversion ratio in all DBH groups, with DBH10 recording the highest growth. The DBH (0–5 %) diets did not alter the leukogram and erythrogram of O. niloticus, whist, the DBH (7.5–10 %) diets badly affected the leukogram and erythrogram of the fish. The DBH7.5 and DBH10 diets significantly increased (p < 0.05) the levels of hepato-renal function indicators. A significant increase (p < 0.05) in the hepatic antioxidant parameters and its related gene expression in the spleen with a lower level of malondialdehyde was detected in the DBH5 and DBH7.5 groups, followed by DBH10 then DBH2.5 compared to DBH0 group. Hepatic and renal tissue architecture showed normal histomorphological structure in DBH (0–10 %), except a mild interstitial lymphocytic infiltration and melano-macrophages proliferative activation could be observed in DBH7.5 to10 %. As a result, the DBH at a percentage up to 5 % could be used as a substitution for FM without affecting the fish growth, health, hematological parameters, the oxidant/antioxidant balance, and hepatic and renal tissue architecture, which serves the sustainable aquaculture industry.

A Connexin Gene (GJB3) Mutation in a Chinese Family With Erythrokeratodermia Variabilis, Ichthyosis and Nonsyndromic Hearing Loss: Case Report and Mutations Update.

Background: Gap junctions formed by connexins are channels on cytoplasm functioning in ion recycling and homeostasis. Some members of connexin family including connexin 31 are significant components in human skin and cochlea. In clinic, mutations of connexin 31 have been revealed as the cause of a rare hereditary skin disease called erythrokeratodermia variabilis (EKV) and non-syndromic hearing loss (NSHL). Objective: To determine the underlying genetic cause of EKV, ichthyosis and NSHL in three members of a Chinese pedigree and skin histologic characteristics of the EKV patient. Methods: By performing whole exome sequencing (WES), Sanger sequencing and skin biopsy, we demonstrate a Chinese pedigree carrying a mutation of GJB3 with three patients separately diagnosed with EKV, ichthyosis and NSHL. Results: The proband, a 6-year-old Chinese girl, presented with demarcated annular red-brown plaques and hyperkeratotic scaly patches on her trunk and limbs. Her mother has ichthyosis with hyperkeratosis and geographic tongue while her younger brother had NSHL since birth. Mutation analysis revealed all of them carried a heterozygous missense mutation c.293G>A of GJB3. Skin biopsy showed many grain cells with dyskeratosis in the granular layer. Acanthosis, papillomatosis, and a mild superficial perivascular lymphocytic infiltrate were observed. Conclusion: A mutation of GJB3 associated with EKV, ichthyosis and NSHL is reported in this case. The daughter with EKV and the son with NSHL in this Chinese family inherited the mutation from their mother with ichthyosis. The variation of clinical features may involve with genetic, epigenetic and environmental factors.

Tumoral and Parenchymal Morphological Assessment in Liver Metastases of Colorectal Carcinoma: Micrometastasis, Peritumoral Lymphocytes, Tumor Budding and Differentiation are Potential Prognostic Factors.

Introduction: Various potential prognostic histopathologic factors for colorectal carcinoma liver metastasis have been proposed. However, there is still no consensus on pathological reporting of colorectal carcinoma liver metastasis resection materials. The aim of this study was to investigate the relation between selected tumoral and parenchymal histopathologic features and prognostic factors for better characterization and prognostic prediction of the patients with colorectal carcinoma liver metastasis. Methods: Hematoxylin-eosin stained slides from 100 patients who underwent hepatic resection were evaluated. Pathologic characteristics; including number of tumor nodules, largest tumor size, status of surgical margin, tumor distance to closest margin, tumor necrosis, the presence of tumor capsule, tumor differentiation, perineural and lymphovascular invasion, micrometastasis, tumor budding, peritumoral lymphocytic infiltrate and parenchymal features including steatosis, steatohepatitis, lobular inflammation, confluent necrosis, hepatocyte ballooning, portal inflammation were assessed. For 49 patients who were treated with preoperative chemotherapy, tumor regression grade and chemotherapy-related parenchymal changes such as sinusoidal damage, venous obstruction, nodular regenerative hyperplasia, steatosis and steatohepatitis were also evaluated. Results: The presence of lymphovascular invasion (p < 0.001), micrometastasis (p=0.004), absent or mild peritumoral lymphocytic infiltration (p =0.013), high tumor budding score (p=0.033) and moderate/poor differentiation (p=0.022) were significantly associated with shorter overall survival. Lymphovascular invasion (p < 0.001) was an independent predictor of mortality in multivariate analysis. Conclusions: We conclude that tumor differentiation, lymphovascular invasion, micrometastasis, peritumoral lymphocytic reaction and tumor budding score are potential prognostic histopathological features and candidates for inclusion in pathology reports of colorectal carcinoma liver metastasis resections.

Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets.

Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (COVID-19). We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti-interleukin-1β (IL-1β), anti-IL-6, and anti-tumor necrosis factor α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19 revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, was detected in postmortem pancreatic tissues, suggestive of β-cell-altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.

P067 Covid- 19 infection as a trigger for immune inflammatory myositis

Abstract Background/Aims Increasing experience in managing patients with COVID-19 infection has demonstrated the development of autoimmune phenomena following infection. We describe a patient with preceding COVID-19 infection who presented with inflammatory immune myositis, positive myositis antibodies and a normal creatine kinase. Methods N/A Results A 61-year-old Caucasian female presented feeling generally unwell and with weakness. She had COVID-19 infection 4 months prior, which necessitated admission to the Intensive Care Unit (ITU), treatment with dexamethasone and oxygen and subsequent discharge with home continuous positive airway pressure (CPAP). Other co-morbidities included atrial fibrillation, chronic kidney disease stage three, hypertension, obesity, recent pulmonary embolism, obstructive sleep apnoea, chronic lymphoedema and hypercholesterolaemia on atorvastatin. Her mobility had been gradually reducing over the previous months to now requiring a wheelchair. Neurological examination demonstrated bilateral proximal lower limb weakness, power 3/5 and an unsafe swallow, for which a naso-gastric tube was inserted. A non-specific erythematous pruritic rash was noted on the arms. Full body Computerised tomography (CT) and Magnetic Resonance Imaging (MRI) of the brain and spine were unremarkable. Creatinine kinase (CK) was within normal limits at 81, and C-reactive protein (CRP) was mildly raised at 36. C3 was low at 0.67 and C4 low at 0.03. Cryoglobulins were not detected. She was positive for antinuclear antibody (ANA) (1:320 titre), Ro-52, PM-Scl75, and anti-La. Anti-dsDNA was negative. Electromyography could not be performed due to the presence of chronic lymphoedema. MRI showed symmetrical STIR hyperintense signal changes in the quadriceps muscles bilaterally. A muscle biopsy showed a small focus of mild lymphocyte infiltration in the endomysial connective tissue, mild increase in acid phosphatase expression in many fibres in dotlike pattern, overexpression of HLA-ABC with deposits of complement found in in endomysial capillaries, consistent with a diagnosis of inflammatory myopathy. Following commenced of 60 mg prednisolone daily, there was a marked improvement in swallowing and the NG tube was removed. A positron emission tomography (PET) scan showed non-specific marrow, splenic and adrenal hyperplasia. The patient was then started on mycophenolate mofetil (MMF), but was switched to azathioprine due to side effects. On review following discharge, the patient continues to require a wheelchair to mobilise, but there has been improvement in her swallow and she reports feeling better within herself. Conclusion Inflammatory myositis is a rare sequela of COVID-19 infection. The development of myositis-specific antibodies post infection has previously been described. This case highlights the significant dysphagia and debility despite a normal CK and the need for a high index of suspicion. Possible triggers of an inflammatory response predisposing to autoimmune phenomena include molecular mimicry, bystander activation, exposure of previously hidden epitopes to activated T cells, activation of Toll-like receptors and activation of the complement system. Disclosure G. Bartminski: None. A. Vijayan: None. K. Beharry: None. D. De Lord: None.