Interstitial Inflammatory Infiltration Research Articles

S2774 Sweet Syndrome as One of the Manifesting Symptoms of Inflammatory Bowel Disease

Introduction: Sweet's syndrome (SS), a subtype of neutrophilic dermatosis (ND), is an uncommon skin disorder characterized by the abrupt appearance of painful erythematous skin lesions, fever, and neutrophilia. Diagnosis of SS is made via biopsy showing a dense neutrophilic infiltrate of the dermis and epidermal sparing. SS is associated with hematologic malignancies or drug reactions and less commonly with inflammatory bowel disease (IBD). Treatment of SS, and other NDs, mirrors treatment of the underlying condition and is typically steroid responsive. Identification is important as SS is an extra systemic manifestation of underlying disease and indicates a poor prognosis. We present an 18 year old male with SS as a manifesting symptom of IBD. Case Description/Methods: An 18 year old male presented with 1 month of abdominal pain, oral ulcerations, hematochezia, and a left lower extremity lesion. He had a diffusely tender abdomen, multiple ulcers bilaterally on his buccal mucosa, cheilitis, and a 1 cm ulcerated lesion on his left leg. He was febrile and blood tests revealed anemia, thrombocytosis, neutrophilia, elevated inflammatory markers, and a positive C-ANCA. His leg and oral lesions were biopsied as well as a cratered esophageal ulcer found during endoscopy. Sigmoidoscopy demonstrated a circular ulceration of the anal mucosa and severe patchy inflammation in the descending and sigmoid colon. He was started on methylprednisolone for empiric treatment of presumed IBD. The skin biopsy showed ND with an interstitial and perivascular inflammatory infiltrate with epidermal necrosis without vasculitis most consistent with SS. He was diagnosed with Crohn’s Disease and has seen improvement of his skin lesions, oral lesions, and abdominal symptoms after a prolonged steroid taper. (Figure) Discussion: While NDs are well described in association with IBD, SS is not a subtype of ND that commonly occurs with less than 100 cases described. Biopsy is the definitive diagnostic study and should be done promptly as ND’s differential includes drug-reaction, malignancy, and the skin lesions may appear similar to infectious lesions. The two former conditions will respond to treatment though may relapse if not identified, and the latter will be exacerbated by immunosuppression. For Physicians treating IBD, knowledge of the appearance of ND can ensure prompt biopsy and initiation, or withdrawal, of appropriate therapies.Figure 1.: Top Row: Mucocutaneous findings in the Mouth and Left Lower Extremity Bottom Row: Perivascular mixed inflammatory infiltrate primarily composed of neutrophils with a few eosinophils present with no evidence of vasculitis. The infiltrate is primarily limited to the dermis.

Histopathological Changes in the Liver, Heart and Kidneys Following Malayan Pit Viper (Calloselasma rhodostoma) Envenoming and the Neutralising Effects of Hemato Polyvalent Snake Antivenom.

Calloselasma rhodostoma (Malayan pit viper) is a medically important snake species that is widely distributed across Southeast Asia. Systemic coagulopathy causing severe haemorrhage and local tissue injury is commonly observed following C. rhodostoma envenoming. However, nephrotoxicity and congestive heart failure were previously reported in a patient who had a long length of hospital stay. In this study, we determined the effect of C. rhodostoma envenoming on cardiovascular disturbances and the associated morphological changes in the liver, heart and kidneys using animal models. We also evaluated the efficacy of Hemato polyvalent antivenom (HPAV; Queen Saovabha Memorial Institute (QSMI) of the Thai Red Cross Society, Thailand) in neutralising the histopathological effects of C. rhodostoma venom. The intravenous (i.v.) administration of C. rhodostoma venom (1000 µg/kg) caused a rapid decrease in mean arterial pressure (MAP) followed by complete cardiac collapse in anaesthetized rats. Moreover, the intraperitoneal (i.p.) administration of C. rhodostoma venom (11.1 mg/kg; 3 × LD50) for 24 h caused cellular lesions in the liver and heart tissues. C. rhodostoma venom also induced nephrotoxicity, as indicated by the presence of tubular injury, interstitial vascular congestion and inflammatory infiltration in the whole area of the kidney. The administration of HPAV, at manufacturer-recommended doses, 15 min prior to or after the addition of C. rhodostoma venom reduced the extent of the morphological changes in the liver, heart and kidneys. This study found that experimental C. rhodostoma envenoming induced cardiovascular disturbances, hepatotoxicity and nephrotoxicity. We also highlighted the potential broad utility of HPAV to neutralise the histopathological effects of C. rhodostoma venom. The early delivery of antivenom appears capable of preventing envenoming outcomes.

Misdiagnosis of neutrophilic erythema of infancy as leukocytoclastic vasculitis: A potential diagnostic pitfall in an infantile inflammatory dermatosis.

The authors declare no conflict of interest. The data that support the findings of this study are openly available in NFEI at https://pubmed.ncbi.nlm.nih.gov/. F IGURE 1 Annular erythematous plaques in an infant. Erythematous annular plaque on the right thigh (A) and progression after 3 weeks (B) F IGURE 2 Histopathology of annular erythematous plaque. Punch biopsy specimen from the right leg shows perivascular and interstitial dermal inflammatory infiltrate (A, ×100) primarily composed of neutrophils (B, ×400). Perivascular and interstitial inflammatory infiltrate with primarily neutrophilic inflammation with occasional admixed eosinophils (C, ×400). Leukocytoclasis is present (D, ×400) and definitive vessel wall damage is not observed (A–D)

Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model.

Acute lung injury (ALI) as a model of acute respiratory distress syndrome is characterized by inflammation, complex coagulation, and hematologic abnormalities which result in the formation of fibrin-platelet microthrombi in the pulmonary vessels with the rapid development of progressive respiratory dysfunction. We hypothesize that a nebulized fibrinolytic agent, non-immunogenic staphylokinase (nSta), may be useful for ALI therapy. First, the effect of the nebulized nSta (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg) on the coagulogram parameters was studied in healthy rats. ALI was induced in mice by nebulized administration of lipopolysaccharide (LPS) at a dose of 10 mg/kg. nSta (0.2 mg/kg, 0.4 mg/kg or 0.6 mg/kg) was nebulized 30 min, 24 h, and 48 h after LPS administration. The level of pro-inflammatory cytokines was determined in the blood on the 8th day after LPS and nSta administration. The assessment of lung damage was based on their weighing and microscopic analysis. Fibrin/fibrinogen deposition in the lungs was determined by immunohistochemistry. After nSta nebulization in healthy rats, the fibrinogen blood level as well as activated partial thromboplastin time and prothrombin time did not change. In the nebulized ALI model, the mice showed an increase in lung weight due to their edema and rising fibrin deposition. An imbalance of proinflammatory cytokines was also found. Forty percent of mice with ALI without nSta nebulization had died. Nebulized nSta at a dose of 0.2 mg/kg reduced the severity of ALI: a decrease in interstitial edema and inflammatory infiltration was noted. At a dose of 0.4 mg/kg of nebulized nSta, the animals showed no peribronchial edema and the bronchi had an open clear lumen. At a dose of 0.6 mg/kg of nebulized nSta, the manifestations of ALI were completely eliminated. A significant dose-dependent reduction of the fibrin-positive areas in the lungs of mice with ALI was established. Nebulized nSta had a normalizing effect on the proinflammatory cytokines in blood— interleukin (IL)-1α, IL-17A, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These data showed the effectiveness of nebulized nSta and the perspectives of its clinical usage in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Sacubitril/Valsartan Improves Progression of Early Diabetic Nephropathy in Rats Through Inhibition of NLRP3 Inflammasome Pathway.

PurposeDiabetic nephropathy (DN), a global disease, is the leading cause of end-stage renal disease. There is a lack of specific treatment for this disease, and early intervention in disease progression is essential. In this paper, we used a rat model of early diabetic nephropathy to explore the therapeutic mechanism of sacubitril/valsartan in rats with early diabetic nephropathy.Materials and MethodsRats were grouped into 1 normal group; 2. Model group (DN group): STZ (45 mg/kg/d) induced early diabetic nephropathy rats; 3. Sac group: DN rats + Sac group (orally, 60 mg/kg/d) for 6 weeks. After 6 weeks, the levels of serum albumin (ALB), glucose (GLU), creatinine (Cr), urea nitrogen (BUN) and 24-h urinary protein excretion were measured. In renal tissue homogenates, NLRP3 inflammasome, proinflammatory factors IL1-β and TNF-α, oxidative stress MDA and pro-fibrotic cytokine TGF-β1 were performed. Histological analysis of kidneys by hematoxylin and eosin (HE), PAS and Masson trichrome staining.Results1. Sacubitril/valsartan (Sac) significantly improved renal hypertrophy, proteinuria and serum albumin levels in rats with early diabetic nephropathy (P < 0.001), and decreased GLU, Scr (P<0.001), and BUN levels (P < 0.01).2. Light microscopy of renal tissues showed glomerular hypertrophy and interstitial inflammatory cell infiltration, and mean glomerular area (MGA) and mean glomerular volume (MGV) were crucially increased in early diabetic nephropathy (P < 0.001), and the Sac group showed reduced renal pathology and improved MGA and MGV (P < 0.001).3. Kidney tissue homogenate levels of NLRP3, Caspase-1, IL1-β, TNF-α, MDA and TGF-β1 were critically, increased in DN rats (P < 0.001), and SOD was significantly decreased. All these indicators above were improved after treatment (P < 0.0001).ConclusionNlrp3-inflammasome promote progression of diabetic nephropathy through inflammation, fibrosis and oxidative stress; sacubitril/valsartan ameliorated early diabetes-induced renal damage by inhibiting NLRP3 pathway activation.

Exposure to particulate matter 2.5 leading to lung microbiome disorder and the alleviation effect of Auricularia auricular-judae polysaccharide.

The aim of the paper is to explore the role of lung microbiome disorder in lung tissue injury induced by exposure to particulate matter with a maximum diameter of 2.5 μm (PM2.5) and the alleviation effect of Auricularia auricular-judae polysaccharide (AAP). Sprague Dawley rats were given PM2.5 suspension at a dose of 20 mg/l twice a week for 8 weeks. Then, 100 mg/kg or 200 mg/kg of AAP was administered to the rats after PM2.5 exposure. The bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at the end of the experiment. The BALF was meant to detect changes in lung microbiome by 16S sequences and cluster analysis, with the application of the principal component analysis and the partial least squares discriminant analysis. The levels of interferon-γ (IFN-γ), and interleukin (IL)-4, IL-8, and IL-10 in lung tissue were detected by the enzyme-linked immunosorbent assay method. The pathological changes in lung tissue were observed by hematoxylin and eosin staining. After PM2.5 exposure, the alveolar septum was widened, and the structures of alveolar walls were destroyed. There was inflammatory cells infiltration in the alveolar space and the interstitial space. Alpha diversity in BALF showed that the Chao1, ACE, Simpson, and Shannon values were increased, and the lung microbiome analysis revealed that the relative abundance of Firmicutes and Clostridium increased, while the relative abundance of Bacteroidetes and Akkermansia decreased. The contents of IFN-γ and IL-8 in lung tissue increased while the content of IL-10 decreased. After the administration of AAP, the alveolar structure damage was alleviated, and the interstitial hemorrhage, edema, and inflammatory cells infiltration were reduced. The Chao1 and ACE values decreased, and the taxonomic abundance values of Akkermansia were much higher. Simultaneously, the contents of IFN-γ, IL-4, and IL-8 decreased, and the content of IL-10 increased. It was found that PM2.5 resulted in lung microbiome disorder, which might lead to the inflammation of lung tissue. It was also revealed that AAP could alleviate the inflammatory damage of lung tissue induced by PM2.5. Int J Occup Med Environ Health. 2022;35(6):651-64.

Predictive prognostic value of glomerular C3 deposition in IgA nephropathy.

IgAN is the most common primary glomerulonephritis worldwide. However, the pathogenesis of IgAN remains unknown. Currently, there is evidence that C3 deposition plays a role in disease development. This study aimed to investigate clinical, pathological features, and prognosis of adult IgAN patients with C3 deposition, as well as explore the role of complement activation in disease progression. A total of 821 patients with biopsy-proven IgAN were included in this study. Patients were divided into three different groups according to their C3 deposition intensity. Clinical and pathological characteristics were compared between groups. Logistic analysis was used to estimate the relationship between C3 deposition and the Oxford scoring system. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of the presence ofC3 deposits on the prognosis of patients with IgA nephropathy. Kaplan-Meier survival analysis was used to evaluate the cumulative incidence of renal progression between groups. Patients with C3 deposition exhibited more severe clinical and pathological features and had a higher score according to the Oxford scoring system. With the increasing intensity of C3 deposition, patients present more hematuria, crescents, heavier interstitial inflammatory cell infiltration and a higher score on segmental sclerosis lesions. Logistic regression identified a positive relationship between C3 deposition and histopathology. Univariate and multivariate Cox regression indicated thatC3 deposition was an independent risk factor for IgANseverity. The Kaplan-Meier survival curves indicated that patients with positive C3 deposition had a worse prognosis compared to those without C3 deposition. Patients with positive glomerular C3 deposition presented with more severe clinical and histopathological characteristics and a higher score on the Oxford scoring system. With the increasing intensity of C3 deposition, IgAN patients were more likely to present with high level ofmicroscopic hematuria, fibrous crescents, interstitial inflammatory cell infiltration, and a higher score on segmental sclerosis lesions. C3 deposition at the time of renal biopsy is likely an independent risk factor for IgA nephropathyseverity and progression.

Multiple skin-colored facial papules in a child

Multiple skin-colored facial papules in a child

The Significance of Crescents on the Clinical Features and Outcomes of Primary Immunoglobin A Nephropathy

BackgroundIt is still controversial whether the proportion of crescents below 50% can be an independent predictive risk factor for poor prognosis in IgAN patients. We reported the significance of different proportions of crescents on the clinical features and the cut-off value of crescents in predicting the occurrence of end-stage kidney disease (ESKD) in patients with IgAN.MethodsWe retrospectively analyzed biopsy-proven primary IgAN patients in Sichuan Provincial People’s Hospital from 2007 to 2019. The patients were divided into 5 groups on the basis of crescent proportion as follows: 0 (n = 647), < 10% (n = 221), 10 to 24% (n = 272), 25 to 49% (n = 80), and ≥50% (n = 22). The primary endpoint was defined as ESKD, and the secondary endpoint was the combined renal endpoint (≥50% reduction in eGFR or ESKD). A validation cohort of 346 patients were enrolled from Affiliated Hospital of Southwest Medical University. Cox regression model and Kaplan-Meier survival analysis were performed.ResultsA total of 1242 eligible patients with biopsy-proven IgAN were recorded in the database, compared with the non-crescent group, patients in the crescent group had lower levels of hemoglobin (Hb) and albumin (Alb), higher levels of blood urea nitrogen (BUN), 24h urinary protein and hematuria, a higher proportion of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubular atrophy/interstitial fibrosis (T1/T2) (p < 0.05). A higher crescent proportion was associated with lower levels of Hb, ALB, eGFR and serum IgG (p < 0.05), higher levels of SCr, BUN, increasing amounts of 24 h urinary protein, increasing proportion of M1 and E1, and increasing severity of interstitial inflammatory infiltration. During the median follow-up of 43 months (range 6-151), 63 individuals (7.0%) reached the primary outcome of ESKD and 99 patients (11.1%) reached the combined renal endpoint. 34(7.5%), 21 (13.3%), 24(12.2%), 14(21.5%) and 6(31.6%) patients reached the combined renal endpoint in the above five groups in crescents 0, <10%, 10∼24%, 25∼49% and ≥50%, respectively. A total of 274(62.6%) cases in the crescent group and 254 (55.7%) cases in the non-crescent group received immunosuppressive therapy. Multivariate Cox regression showed that crescents ≥50% was an independent risk factor for the progression of ESKD (p = 0.003) and crescents ≥25% was an independent risk factor for the combined renal endpoint(p < 0.001). The receiver operating characteristic curve showed that IgAN patients with crescents ≥43.7% had a higher risk of ESKD, even with immunosuppressants (Sensitivity = 75.7%,specificity = 89.6%,p < 0.001). This discovery cohort and the validation cohort further confirmed that patients with crescents <43.7% had better renal prognosis than those with crescents ≥43.7% in the whole group and those with immunosuppressants (p < 0.001).ConclusionIgAN patients with crescents had more severe clinicopathological features and poorer prognosis. Crescents ≥50% was an independent risk factor for the progression of ESKD and crescents ≥25% was an independent risk factor for ≥50% reduction in eGFR or ESKD in treated and untreated IgAN patients. Crescents ≥43.7% was an independent risk factor for ESKD in those with immunosuppressants.

Telmisartan ameliorates LPS-induced pneumonia in rats through regulation of the PPARγ/NF-κB pathway.

Pneumonia is a common disorder of the respiratory system associated with inflammation. Telmisartan (TEL) has been reported to treat inflammatory-related diseases. The current study aimed to investigate the possible role and action mechanism of telmisartan on lipopolysaccharide (LPS)-induced pneumonia in rats. Forty male Sprague Dawley rats aged 8 weeks were assigned into four groups ad libitum: a control group received saline only, an experimental group received LPS, a group received telmisartan (5 mg/kg), followed by LPS treatment, and a group received telmisartan (10 mg/kg), followed by LPS treatment. The LPS (2 mg/kg) and equal saline were administered intratracheally. Telmisartan was administered orally 5 days before LPS. After LPS treatment for 24 hr, bronchoalveolar lavage fluid (BALF) and serum were collected for the analysis of cell counts and/or cytokines. Lung tissues were used to perform histological examination, to assess oxidative stress levels, and to determine the levels of PPARγ/NF-κB pathway-related proteins. Rats that received LPS treatment exhibited high levels of lung wet/dry ratio, alkaline phosphatase, lactate dehydrogenase, BALF polymorphonuclear leukocytes count, inflammatory cytokines, and oxidative stress. Meanwhile, LPS also resulted in severe interstitial edema and inflammatory cell infiltration. Interestingly, telmisartan by oral administration markedly ameliorated the adverse effects of pneumonia in rats caused by LPS. In addition, western blotting further revealed that telmisartan could activate PPARγ and repress NF-κB (p65). Telmisartan is protective against pneumonia through inhibition of the inflammation and oxidative stress via the PPARγ/NF-κB pathway.

MO054: Histological Findings in Drug-Induced Acute Interstitial Nephritis

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) represents an important cause of acute kidney injury. The most common etiology of AIN is drug-induced disease. Definitive diagnosis of AIN requires renal biopsy. Despite this, there is a lack of consensus regarding precise histological diagnostic criteria, and the clinical significance of common histological findings is uncertain. The aim of this study was to explore the histological characteristics of drug-induced AIN and to evaluate their impact on the renal outcome. METHOD We conducted a retrospective study that included patients with biopsy proven drug-induced AIN, followed in the department of nephrology of Charles Nicolle hospital in Tunis during the period between 1990 and 2019. Histological diagnosis of AIN was based on the presence of an interstitial inflammatory cell infiltrate with or without fibrosis. RESULTS During the period of the study, we collected 69 cases of biopsy proven AIN. The diagnosis of drug-induced AIN was performed in 23 patients (33%), with a medium age of 35 years. In eight patients (35%), nonsteroidal anti-inflammatory drugs were the culprit, followed by antibiotics in six patients (26%) and other drugs in three cases (13%). In six patients (26%), no single drug could be identified as the culprit, and these were classified as multidrug causes. The presence of acute kidney disease was the main indication for the kidney biopsy. All cases were characterized by a prominent tubulointerstitial inflammatory cell infiltrate. Interstitial infiltration was mild in three cases (13%), moderate in five cases (17%) and severe in 15 cases (65%). The interstitial infiltrate consisted predominantly of lymphocytes. The presence of eosinophils has been noted in 10 cases (43%). Interstitial granulomas were noted in two patients (8%). Interstitial edema and tubulitis were observed in 13 (56%) and 6 cases (26%), respectively. In seven patients (30%) interstitial fibrosis was present, and four patients (17%) had mild-to-moderate tubular atrophy, whereas tubular necrosis was present in seven cases (30%). After a mean follow up of 24 months, eight patients (35%) progressed to chronic kidney disease. Histological factors associated with poor renal outcome, were interstitial fibrosis (P ˂ 0.001) and tubular atrophy (P = 0.01). Patients with interstitial edema (P ˂ 0.001) or tubulitis (P = 0.005) had a better renal prognosis. CONCLUSION Renal biopsy is required to establish a definitive diagnosis of drug-induced AIN. Nevertheless, it is not carried out in a systematic way. The composition of cells in the interstitial infiltrate may at times be helpful in determining the etiology of AIN. In particular, the presence of a considerable proportion of eosinophils favors a diagnosis of drug-induced AIN. Moreover, during drug-induced AIN, histological data have a great prognostic value. In our study, the main histological prognostic factors were interstitial fibrosis, tubular atrophy, interstitial edema and tubulits. Further studies are needed to validate these results and establish a score based on histological data in order to predict renal outcome during drug-induced AIN.

MO194: A Rare Case of Secondary Haemolytic Uremic Syndrome after ANTI-SARS-COV-2 Vaccination

Abstract BACKGROUND AND AIMS Haemolytic uremic syndrome (HUS) is a rare disease characterized by macroangiopathic haemolytic anaemia, thrombocytopaenia and severe AKI, belonging to the thrombotic microangiopathies (TMAs). It is divided into typical and atypical HUS: the first one occurs most frequently in children within the first 5 years of life and it is associated with Shiga-like toxin producing Escherichiacoli infection; the second one (aHUS) is less common (10%) and it is due to complement abnormalities with coexisting disease or trigger such as autoimmunity, transplantation, cancer, infection, certain cytotoxic drugs or pregnancy. There is an increasing interest in SARS-CoV-2 infection as new trigger for complement activation. Nine cases of aHUS were recently associated with COVID-19, most of them occurring within 1 month from the infection. Available data suggest that SARS-CoV-2 is a potential trigger for aHUS: it can induce an over inflammatory state and to activate coagulation and complement pathway. Likewise, mRNA-based vaccines against COVID-19 inducing the expression of SARS-CoV-2 spike protein to stimulate immune recognition and antibody response could be a suitable trigger for HUS. METHOD We report the case of a 17-year-old woman, who presented at our emergency department with fever, dyspnoea, acute kidney injury AKI III with anuria, hypertension, severe anaemia, no diarrhoea, severe thrombocytopaenia and myocarditis, about 2 weeks after the first administration of SARS-CoV-2 vaccine (Comirnaty) and recent exposition to SARS-CoV-2 positive individual. SARS-CoV-2 nasal PCR swab was negative (as well as successive ones) and she was immediately admitted to paediatric intensive care unit and treated with transfusions and haemodialysis. Laboratory exams suggested a thrombotic microangiopathy with normal ADAMTS-13 activity and no E. coli infection. She underwent a renal biopsy that confirmed our hypothesis of aHUS: wrinkled capillaries, subendothelial expansion, mesangiolysis and rare thrombi in capillaries lumen. Arterioles had intimal proliferation with mucoid oedema who gave rise to onionskin like lesion that obliterates lumens. One glomerulus showed extracapillary proliferation (crescent), and there was interstitial lymphomonocytic inflammatory infiltration in the nearby. Also signs of acute tubular injury and atrophy were reported. Positive stain to fibrinogen in the arterioles at immunohistology was noted. She immediately performed genetic exams for aHUS-related complement mutations and she started immunosuppression with corticosteroids and eculizumab infusions. After 2 months of eculizumab, she was still oliguric, requiring renal replacement therapy. Genetic analysis showed no mutations. Therefore, she was examined for other genetic causes of thrombotic microangiopathies. RESULTS Finally, came to light that she had high levels of homocysteine, and she was diagnosed with secondary HUS associated with cobalamin C deficiency, which manifests with methylmalonic aciduria and homocystinuria due to a recessive mutation in the MMACHC gene, causing a cobalamin C type deficiency, which is the common functional variant of vitamin B12. After metabolic therapy with hydroxocobalamin, she gradually recovered diuresis and partially renal function without need for replacement therapy. CONCLUSION Reports from immunization programs show as myocarditis and thrombotic thrombocytopaenia are considered among main serious complications caused by COVID-19 vaccines, representing 12.6 cases per million doses and 0.73 cases per 100 000, respectively. This interesting case probably supports data about the role of mRNA-based anti-SARS-CoV-2 vaccines like a precipitant factor for TMAs. Moreover, our patient turned out to be an extremely rare case of HUS secondary to cobalamin C deficiency, that is generally diagnosed in early infancy and show typically neurological symptoms (absent in our case). Probably, the mRNA-based vaccine acted like ‘a second hit’, but existing predisposition should always be investigated including also the less frequent forms.

MO306: Pharmacologic versus Immunologic Acute Interstitial Nephritis Long Term Outcome. Are There any Differences

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) is a common cause of acute renal failure affecting between 5% and 27%. It is characterized by the presence of interstitial inflammatory infiltrate, tubulitis and edema. A considerable number of cases develop chronic kidney disease (CKD), with a linear relationship observed with the diagnosis delay. There are different etiologies, most importantly those secondary to drug exposure and those related to immunological diseases. To the date, there are few studies comparing both etiologies. In this regard, the aim of this study is to determine difference between both etiologies by comparing clinical, histological and renal prognosis. METHOD A retrospective, observational, single-center study was performed. Clinical and histological characteristics of patients with a first episode of pharmacological or immunological AIN, confirmed by renal biopsy between 1998 and 2020, were compared. Histological analysis was measured by semi-quantitative methods. RESULTS A total of 67 patients have been described, with a mean age of 68 ± 13 years, 56% were women. The baseline creatinine was 93.8 umol/L with an eGFR (CKD-EPI) of 67 mL/min/1.73 m2; mean follow-up time was 63 ± 55 months. A total of 46 patients presented pharmacological AIN, being NSAIDs and antibiotics the most frequent agents, 21 patients with AIN associated to immunological diseases, being Sjögren’s syndrome the most frequent. Previous CKD was present in both groups, with 42% in immunological AIN versus 32% in pharmacological AIN, of which stage 3a CKD was more frequent in drug-mediated AIN (69% versus 33%) as opposed to stage 3b CKD was more frequent in immunological AIN (67% versus 19%). However, no significant differences were observed in the estimated glomerular filtration rate when comparing both groups. A longer diagnostic delay was observed in patients with immunological, defined as the elapsed time from renal function deterioration to the performance of renal biopsy, 93 ± 210 versus 13 ± 15 days (P = .021). However, creatinine at the time of diagnosis was higher in patients with pharmacological cause (380 ± 199 versus 252 ± 246 umol/L; P = .0002), leukocyturia was more frequent in the pharmacological AIN group without differences in the percentage of hematuria or proteinuria. In histological analysis, there were no significant differences in interstitial infiltrate, renal fibrosis or tubular atrophy. Once the biopsy was performed, treatment was started in all patients before the 5th day. In pharmacological AIN, the causative drug was withdrawn and corticosteroids were administered to the majority of patients. Out of 46 patients, 7 (15%) patients of the pharmacological AIN group, the drug was withdrawn with no additional treatment, 4 of them progressed to end-stage kidney disease (ESKD). In the immunological AIN group, most of patients were treated with corticosteroids or immunosuppressants. Out of 21 patients, 3 patients (14%) were not treated and progressed to ESKD. Treatment time was longer in patients with immunologic AIN (290 ± 195 versus 141 ± 168 days; P = .004). No differences were observed in creatinine or glomerular filtration rate at 6, 12 months, end of treatment or last control. The recovery of renal function was also analyzed, observing a higher percentage of complete recovery in patients with AIN associated with immunological diseases at 6 months (43% versus 24%) and at 12 months of follow-up (58% versus 29%); however, did not reach statistical significance. During follow-up, 2/46 (4%) recurrences were recorded in patients with pharmacological AIN and 6/21 (28%) in the immunological AIN group. CONCLUSION Despite the fact that patients with AIN associated with immunologic disease have a higher rate of previous CKD related to diagnostic delay and a higher rate of relapses, we observed that the evolution/progression of renal function was similar to the patients with pharmacological AIN. This could suggest that immunological AIN has a more favorable clinical course or better response to the treatment.

In vivo study of cardioprotective effect of bay leaf (Syzygium polyanthum) extract

Background: The excessive use of chemotherapy drugs such as doxorubicin might induce cardiovascular diseases. Heart-specific biomarker enzymes such as LDH and BNP indicated the early signs of cardiotoxicity. However, there is no report on the effect of bay leaf on LDH and BNP nor its bioactive compounds and histopathology analysis.Objective: This study aims to determine the cardioprotective effect of Ethanol Extract of Bay Leaf (EEBL) based on phytochemical analysis, LDH and BNP levels, and cardiac histology of rats administered with doxorubicin.Methods: About 24 Wistar rats were divided into six groups treated with 100 mg/kg BW, 300 mg/kg BW, and 500 mg/kg BW of EEBL with CMC-Na 0.5 %, vitamin E, and doxorubicin. Preconditioning was 14 days, followed by 21 days of intraperitoneal administration. LDH and BNP parameters were measured on days 1st, 7th, 14th, and 20th. Histology analysis was conducted on day 21st.Results: Dark green EEBL showed sufficient physical quality and properties for practical application in pharmacy. EEBL has significantly affected LDH, BNP, and cardio recovery dose-dependent. The most effective doses were observed at 500 mg/kg BW, and its performance is not statistically different from those of the commercial vitamin E. The histopathological images revealed significant improvements in interstitial edema, wavy fibers, hemorrhage, intracellular vacuole, and inflammatory cell infiltration. Here we report six bioactive compounds obtained from EEBL have cardioprotective effects; Neophytadiene, squalane, phytol, methyl palmitate, stigmasterol, and 9,12-Octadecanoic acid methyl ester.Conclusion: This study has shown the promising potential of bay leaf extract as a cardioprotector with sufficient quality pharmacological standards.

Cardiac arrest with successful cardiopulmonary resuscitation and survival induce histologic changes that correlate with survival time and lead to misdiagnosis in sudden arrhythmic death syndrome

BackgroundSudden arrhythmic death syndrome (SADS), defined as sudden cardiac death (SCD) with a morphologically normal heart, is an important cause of sudden death. Hypoperfusion due to cardiac arrest followed by successful cardiopulmonary resuscitation (CPR) may induce histologic changes that mimic pathologic conditions. Detailed characterisation of such features and whether they could confound SADS diagnosis are not described. MethodsRetrospective observational study analysing all consecutive cases of sudden death prospectively referred to a UK national cardiac pathology centre between 2017 and 2021. Cases showing hypoperfusion features were identified after review of clinical information and examination by expert cardiac pathologists. ResultsOut of 2,568 SCD cases, 126 (4.9%) were identified with hypoperfusion changes. Macroscopically, the commonest finding was left ventricular focal or diffuse subendocardial haemorrhage (13.5%). Microscopically, haemorrhage and contraction band necrosis (n = 50, 37.7%), subendocardial acute infarction (n = 44, 34.1%), interstitial mixed inflammatory cell infiltrates (n = 31, 24.9%), healing granulation tissue (n = 9, 7.1%) and subendocardial fibrosis (n = 1, 0.7%) were observed. These changes correlated to duration of survival following resuscitation. In a subcohort of 41 cases, autopsy pathologists misinterpreted such changes as ischaemic myocardial infarction (n = 7; 17%), myocarditis (n = 5; 12.1%), or other pathologies (n = 2; 4.8%) in 14 SADS cases. ConclusionWe provide a comprehensive characterisation of hypoperfusion-related changes in the heart following successful CPR with survival, which are time related. These features can lead to diagnostic confusion among pathologists but knowledge of history of resuscitation with survival should help with general and expert pathology assessment and improve SADS diagnostic yield, prompting genetic screening of decedents’ relatives.

Effect of olive oil on the stomach of adult male albino rats with induced liver fibrosis

Background Liver fibrosis proceeds to portal hypertension, and portal hypertensive gastropathy is considered its main complication. Olive oil is associated with human health benefits. Aim To study the effect of olive oil on the stomach after induction of liver fibrosis. Materials and methods A total of 50 healthy adult male albino rats were randomly divided into two groups, including group I (control group) and group II (experimental group), which were subdivided into four subgroups: olive oil-treated subgroup IIa received 5 ml/kg body weight olive oil daily by an orogastric tube for 4 weeks, subgroup IIb received 0.1 ml/100 g body weight carbon tetrachloride (CCL4) by intraperitoneal injection twice per week for 4 weeks, subgroup IIc received both olive oil and CCL4 at the same dose of subgroups IIa and IIb for the same period, and subgroup IId received CCL4 for 4 weeks and then olive oil was given alone for another 4 weeks as the same dose in subgroups IIa and IIb. Stomach specimens were processed for histological and immunohistochemical study. Results Subgroup IIb showed disorganized and atrophic gastric glands with severe interstitial hemorrhage and diffuse inflammatory infiltrates. The parietal cells had vacuolated cytoplasm with irregular nuclei, and others had karyolitic nuclei with vacuolization of the cytoplasm of some chief cells. Subgroup IIc showed significant improvement, and subgroup IId showed nonsignificant improvement. Conclusion The use of olive oil partially improved the histological changes in the stomach as a result of liver fibrosis.

POS-028 A CASE REPORT OF ACUTE INTERSTITIAL NEPHRITIS AFTER HERBAL SUPPLEMENT INTAKE IN A 45-YEAR-OLD FEMALE

Acute Interstitial Nephritis (AIN) is a major cause of acute kidney injury that remains underdiagnosed. AIN is characterized by interstitial inflammatory infiltrates and presents with fever, rash, eosinophilia, and renal failure. Etiologies include drugs, systemic diseases, and infections. Herbal and supplement usage have also increased over the past years but very little evidence associating its usage with AIN, especially in the Philippines. The case reports a patient who developed AIN after intake of herbal supplement.

Bacteriological and pathological investigations on the preputial glands of one-year-old C57BL/6NCrl mice maintained in individually ventilated cages.

Spontaneous infections of the preputial glands represent overlooked health problems in mice that could raise welfare concerns and potentially confound scientific experiments. Agents involved in preputial gland infections have rarely been investigated, with opportunistic pathogens of laboratory animals usually detected in inflamed preputial glands. The aim of this study was to investigate the prevalence of bacterial infection in the preputial glands and the relationship between haematological and pathological changes and infection status. We analysed 40 preputial glands from 20 one-year-old C57BL/6NCrl male mice by using bacteriology, haematology and pathology. Bacteria were isolated from 16/20 (80%) mice, for a total of 32/40 (80%) examined preputial glands. Enterobacter cloacae, Pasteurella spp., Klebsiella spp. and Staphylococcus aureus were identified in 35%, 17.5%, 15% and 12.5% of the examined glands, respectively. Preputial gland inflammation was identified in 29/40 (72.5%) glands and was classified as chronic interstitial adenitis in 27 cases and suppurative adenitis in the remaining two glands. No haematological changes were found in mice with infected glands. Histologically, the presence of intralesional bacteria, intraluminal necrotic material, intraluminal keratin accumulation, interstitial inflammatory cell infiltrate and granulocytes (intraluminal and/or interstitial), along with total inflammatory score and total histopathological score, were significantly increased in infected glands and correlated with the bacterial load. Most severe inflammatory changes were identified after S. aureus infection, while ductal hyperkeratosis was significantly increased in glands infected with Klebsiella spp. In conclusion, preputial gland infection was a common event in one-year-old C57BL/6NCrl mice, and bacterial load correlated with pathological findings, while systemic effects were not highlighted by haematology.

In Vitro, In Vivo, and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection.

The sesquiterpene lactones cumanin, helenalin, and hymenin and their semisynthetic derivatives were evaluated against Trypanosoma cruzi epimastigotes. The cytotoxicity of the compounds was evaluated on murine splenocytes. Cumanin diacetate was one of the most active and selective compounds [IC50 = 3.20 ± 0.52 μg/mL, selectivity index (SI) = 26.0]. This sesquiterpene lactone was selected for its evaluation on trypomastigote and amastigote forms of the parasite. The diacetylated derivative of cumanin showed moderate activity on trypomastigotes (IC50 = 32.4 ± 5.8 μg/mL). However, this compound was able to efficiently inhibit parasite replication with an IC50 value of 2.2 ± 0.05 μg/mL against the amastigote forms. Cumanin diacetate showed selectivity against the intracellular forms of Trypanosoma cruzi with an SI value of 52.7. This cumanin analogue was also active on an in vivo model of Chagas disease, leading to a reduction in the parasitemia levels in comparison with nontreated animals. Histopathological analysis of skeletal muscular tissues from treated mice showed only focal interstitial lymphocyte inflammatory infiltrates with slight myocyte necrosis; in contrast, nontreated animals showed severe lymphocyte inflammatory infiltrates with necrosis of the myocytes. A molecular docking study of cumanin and its derivatives on trypanothione reductase from T. cruzi (TcTR) was performed. The results of ΔG docking achieved let the identification of diacetylated and O-alkylated derivatives of cumanin as good inhibitors of TcTR. Cumanin diacetate could be considered a potential candidate for further studies for the development of new therapies against Chagas disease.

Abstract 11186: A Case for Exercise-Induced Arrhythmogenic Right Ventricular Cardiomyopathy

Introduction: Sudden cardiac arrest has been documented in athletes, often secondary to left ventricular (LV) hypertrophy or previously undetected genetic conditions. Some athletes, however, experience these events without evidence of either LV or genetic disease. A hypothetical exercise-induced arrhythmogenic right ventricular cardiomyopathy (ARVC) has been previously described by La Gerche and colleagues, acquired through repeated, intense endurance exercise and associated cardiac remodeling rather than genetic inheritance. We present a case report of an endurance athlete presenting with ventricular tachycardia (VT), suspected to be secondary to exercise-induced ARVC. Results: A 40 year-old male endurance athlete was brought to the emergency department when he collapsed following a race in 2006. Upon arrival, he was in sustained wide-complex tachycardia at a rate of 200-220 BPM. Following conversion with IV amiodarone, left heart catheterization was performed, showing no significant coronary disease and LV ejection fraction (EF) measured 30-35%. He then underwent right ventricular outflow tract ablation. Cardiac MRI was inconclusive for ARVC. Biopsy was performed, negative for amyloidosis but with “focal mild to moderate chronic interstitial inflammatory infiltrates associated with focal muscle fiber necrosis.” Genetic testing was negative for pathologic variants or mutations associated with ARVC. Echocardiogram from 2020 showed EF 40-44% with significant RV enlargement and dysfunction. He required repeat VT ablation in 2010, 2014, and 2017. Arrhythmogenic scar was identified by electrophysiology mapping to be located at the sub-tricuspid RV. In combination with the prior RV outflow tract ablation, this is suggestive of the theoretical exercise-induced ARVC. Conclusions: There is still debate regarding right ventricular remodeling in endurance athletes. Increased volume and pressure in response to demand for cardiac output associated with this intense exercise has been proposed as a possible etiology of RV cardiomyopathy in athletes without identifiable genetic predisposition. Our case report supports this hypothesis.