Pharmaceutical Effects on Placental Morphology in Women with Gestational Diabetes Mellitus

Objective: The purpose of this study was to see how food organization and Metformin affected placental morphology in women with GDM. Methods: 66 GDMs were registered after providing informed consent permission. 35 patients of GDM through blood sugar levels 140 mg/dl remained allocated Set B (2500-3000Kcal/day and 30-minute walk three times a week). They remained reserved on diet control, while 34 patients of GDM through blood sugar levels >140 mg/dl have been delegated Set C and remained reserved on diet with tablet Metformin (550mg TDS). Lastly, 28 healthy pregnant women remained retained in Set A as controls. Placentas were stored and analyzed for morphology after delivery. Results: Heavy placentae thru extensive villous immature, charangoists, and syncytial knots were observed in set B, while fibrinoid necrosis and calcification were observed in set C. Placental and cord width were significant in Set B against A, but only cord width was relevant in Set C against A in gross morphology. In light microscopy, charangoists, infarction, and syncytial loops showed detected in sample 2 against with a villous maturity; moreover, charangoists and syncytial knots have been found in appendix B versus C placental width, but C versus A results were negligible. Conclusion: In comparison to the diet group, metformin exhibited beneficial benefits on placental morphology that were equivalent to normal controls.

Methimazole-Induced ANCA Vasculitis: A Case Report

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves’ disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m2), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm3, platelets 238,000/mm3, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m2) and negative p-ANCA.

Bartonella quintana Infection Manifesting as Leucocytoclastic Vasculitis Rash

We present the first case described in the literature of leucocytoclastic vasculitis due to Bartonella quintana infection. A 73-year-old woman presented to the hospital with persistent fevers, retro-orbital headache, generalized weakness, and left lower thigh pain for one week. She was found to have truncal and proximal lower extremity papules and small plaques. Serology revealed Bartonella quintana IgM titer of 1:256 with undetectable Bartonella quintana IgG and undetectable Bartonella henselae IgG and IgM. Skin biopsy of an abdominal lesion revealed fibrinoid necrosis of vessel walls in the superficial and mid-dermis consistent with leucocytoclastic vasculitis. Doxycycline 100 mg orally twice daily was initiated, after which she had defervescence within 36 hours and rapid improvement of other presenting symptoms.

Charcot–Bouchard aneurysms revisited: clinicopathologic correlations

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Hypertension and cerebral amyloid angiopathy (CAA) are the most common causes of primary ICH, but the mechanism of hemorrhage in both conditions is unclear. Although fibrinoid necrosis and Charcot–Bouchard aneurysms (CBAs) have been postulated to underlie vessel rupture in ICH, the role and significance of CBAs in ICH has been controversial. First described as the source of bleeding in hypertensive hemorrhage, they are also one of the CAA-associated microangiopathies along with fibrinoid necrosis, fibrosis and “lumen within a lumen appearance.” We describe clinicopathologic findings of CBAs found in 12 patients out of over 2700 routine autopsies at a tertiary academic medical center. CBAs were rare and predominantly seen in elderly individuals, many of whom had multiple systemic and cerebrovascular comorbidities including hypertension, myocardial and cerebral infarcts, and CAA. Only one of the 12 subjects with CBAs had a large ICH, and the etiology underlying the hemorrhage was likely multifactorial. Two CBAs in the basal ganglia demonstrated associated microhemorrhages, while three demonstrated infarcts in the vicinity. CBAs may not be a significant cause of ICH but are a manifestation of severe cerebral small vessel disease including both hypertensive arteriopathy and CAA.

MO308COULD THE PRESENCE OF ANCAS IN IGA NEPHROPATHY WITH CRESCENTS HAVE A CLINICAL IMPLICATION?

Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis. The presence of ANCAs in this pathology represents a rare coincidence. However, it is not clear if the presence of IgA or IgG ANCAs in these patients could have clinical significance. We aim to describe the presence of IgA and IgG ANCAs in patients diagnosed with IgAN with crescents, and its possible clinical implications. Method Retrospective study from 2013 to 2020, it included all patients diagnosed by kidney biopsy of IgAN with extracapillary proliferation. Outpatient follow-up time was up to 24 months. Demographics and clinicopathologic data, ANCAs subtype, characteristics of the biopsy and treatment at the time of diagnosis/follow up was recollected. Results From 2013 to 2020, 17 adults were diagnosed with IgAN and extracapillary proliferation. 5 patients presented ANCAs, 3 (17%) were IgA ANCAs and 2 (11%) were IgG ANCAs. At diagnosis, the median age was 48 years old (27-75 years, sd. 15), with 9 women (52%). At the time of diagnosis, the most common clinical presentation was hypertension (71%). The laboratory analysis showed that median hemoglobin was 11.7 mg/dl (8.4-14.9 mg/dL, sd. 1.5), median creatinine was 2.2 mg/dL (0.55-5.7 mg/dL, sd. 1.4) and median proteinuria was 3.5 g/mgCr (0.1-12 g/mgCr, sd. 3.5). 7 patients (41%) presented extracapillary proliferation less than 25%, 7 patients presented it between 25% and 50%, and 3 patients (17%) had it in more than 50%. 5 (30%) patients presented fibrinoid necrosis. 1 (6%) patient needed renal replacement therapy upon admission. In terms of treatment, all patients with ANCAs IgAN received endovenous steroids and cyclophosphamide. The mean follow-up time was 6 months. Oral steroids (59%) and mycophenolate (41%) were the most frequent treatments. At six months, the median creatinine was 1.9 mg/dL (0.4-7, sd. 1.78) and the median proteinuria was 1.45 g/gCr (0.12-5.9, sd. 1.84 g/gCr). 3 patients developed end-stage chronic kidney disease and requiring substitute renal therapy; 4 patients died. Statistical analysis did not show differences in clinical characteristics, demographics, kidney function, proteinuria, need for renal therapy replacement or mortality according to the presence or subtype of ANCA. ANCA negative patients presented less than 25% of extracapillary proliferation in renal biopsy (p = 0.04). ANCA positive patients presented more fibrinoid necrosis than ANCA negative patients (p=0.01). Conclusion Given the limited size of our sample, our results do not allow us to be conclusive, showing no significant differences between the ANCA subtypes. However, from the point of renal biopsy, it is observed that patients with negative ANCAs present less extracapillary proliferation; and that patients ANCA positive presented more fibrinoid necrosis.

MO080HISTOLOGIC CLASSIFICATION OF ANCA-ASSOCIATED GLOMERULONEPHRITIS – ARE THERE OTHER MORPHOLOGICAL FEATURES THAT CAN BETTER DESCRIBE MIXED GROUP?

Background and Aims In 2010 a new histopatological classification for ANCA-associated GN (ANCA GN) was developed – the Berden classification. It is composed of four categories – focal, crescentic, sclerotic and mixed - based on the predominance (≥50%) of normal glomeruli, cellular crescents, and globally sclerotic glomeruli, respectively. The mixed category, related to an intermediate renal outcome, has no glomerular feature predominating. Our aim was to evaluate other histopathological characteristics that could be significant in the mixed group and their impact on survival and renal outcome. Method This is a multi-center retrospective observational study which included patients with ANCA GN who were submitted to kidney biopsy at the time of clinical diagnosis, between 2013 and 2018. Several histopathological data were analysed, including percentage of cellular, fibrocellular and fibrous crescents; presence of fibrinoid necrosis, interstitial hemorrhage, tubular atrophy ant interstitial fibrosis. Clinical data such as need of dialysis at presentation and death, during a 2 year follow up period, were also examined. The patients were classified accordingly to the histopathological Berden classification. For statistical analysis purposes they were divided in two groups: mixed and non-mixed. Categorical variables are presented as frequencies and percentages, continuous variables as means and standard deviations, or medians and interquartile ranges (IQR) for variables with skewed distributions. Statistical analysis was performed using SPSS version 25 for Windows. Results We observed 51 ANCA GN kidney biopsies: 68.5% (n=35) from mixed, 11.8% (n=6) from crescentic and sclerotic and 7.8% (n=4) from focal category. In average, the biopsies contained 10.4±4.8 glomeruli. The percentage of fibrous crescents was significantly higher in mixed than non-mixed group (16.1±18.6% vs 7.2±17.9%; p=0.037). Although not statistically significant, the percentage of fibrocellular crescents was higher (10.3±20.9 vs 6.2±12.5; p=0.512) and the percentage of cellular crescents was lower (15.4±18.2 vs 34.3±37.7; p=0.072) in mixed group. The presence of fibrinoid necrosis (54.3% vs 87.5%; p=0.021) and fibrinoid necrosis with cellular crescents (34.3% vs 68.8%; p=0.022) were both lower in mixed category. There was no difference in the need of dialysis at presentation between both groups, but the percentage of fibrous crescents was a predictor of dialysis induction at admission in all cases [p=0.009; adjusted odds ratio (OR) 1.053 (CI: 1.013–1.096)]. Deaths were significantly higher in mixed group (34.3% vs 6.3%; p=0.033). Conclusion There are other morphological aspects that seem to be relevant in the characterization of different histological classes of ANCA GN. Having more chronic lesions, like the percentage of fibrous crescents, and a less frequency of acute lesions, such as fibrinoid necrosis, proved to be relevant in the mixed group and may be associated to the higher mortality in this class. Besides, the percentage of fibrous crescents was itself a predictor of the need of dialysis, which highlights the importance of assess other characteristics, in addition to those included in the current ANCA GN classification. However, further studies and larger samples are needed to evaluate better the importance of other morphological features in this classification and their influence on survival and renal outcome of these patients.

Morphological Peculiarities of Trophic Ulcers of Venous Etiology after Cord Blood Stem Cell Transplantation

The aim. The research deals with analysis of the degree of regenerative processes activity in patients with trophic venous ulcers of the lower extremities that do not heal for a long time on the background of cell transplantation of cord blood stem cells and without. The study involved 32 patients with long-term non-healing trophic venous ulcers of venous etiology. Results and discussion. The study results showed that the healing process of the main group patients began in the first days after transplantation to reduce pericellular edema and inflammatory hyperemia of the soft tissues around the ulcer. When examining the histological features of the central skin ulcers of patients in the control group on the fifth day after treatment, we found out that the bottom surface of the ulcers was covered with homogeneous masses of the type of fibrinoid necrosis. Ulcers had a variable depth, in some places reached the fiber, with sweat and sebaceous glands, hair follicles in the course of defects were completely destroyed, in these places there were hemorrhages and young granulation tissue. In patients of the main group, the surface of the bottom of the ulcer was covered with homogeneous masses of fibrinoid necrosis, but the masses of fibrinoid necrosis were visually expressed three times less than in the control group, but the most important was that they always alternated with "veins" consisting of cells type of lymphoid. Immunohistochemical analysis for Willebrand factor in patients of the main group revealed unevenly scattered small compact groups of positively stained cells, which should be evaluated as foci of neoplasms of blood vessels more evenly distributed among the blood vessels of granulation tissue, in contrast to the control group. On the 14th day of the clinical study at the bottom of the ulcer in the main group there were morphological signs of better maturation of granulation tissue, as seen by more uniform and intensive processes of collagen fiber formation (increase in specific volume of collagen fibers) and blood vessels (decrease in specific volume of blood vessels) and the maturation of lymphoid (polypotent) cells into fibroblasts with more complete production of vimentin in them and endothelial cells with more complete production of Willebrand factor in them. It should be noted that there was a more complete resorption of fibrinoid necrosis masses in the main observation group compared to the control group of patients, which should also contribute to faster and more complete healing of the ulcer

Multiple myeloma characterized by synovial fibrinoid necrosis: a case report

A number of patients with multiple myeloma (MM) have joint lesions with the main feature of amyloidosis or tumor cell infiltration. We report a case of MM that presented as synovial fibrinoid necrosis. The rarity of this condition and the difficulty diagnosing the disease are discussed. In addition, we discussed the characteristics of amyloid arthropathy and the findings in this case.

Pulmonary artery thrombosis as one of the crucial pathonorphological signs of COVID-19: results of 7 autopsies and literature review

Pulmonary artery thrombosis is one of the crucial mechanisms of severe COVID-19 development. Histological examination reveals widespread microvascular thrombosis in 87 % and large branches pulmonary artery thrombosis in 13 % of deceased patients. Caused by viral and immune cytotoxic effect thrombotic lung vasculopathy appears to be the main trigger of pulmonary artery thrombosis. In this study we examined 7 lungs obtained from patients who died from COVID-19. Thrombotic lung vasculopathy was typical sign of all 7 lungs. Endothelial cell destruction, media fibrinoid necrosis, neutrophil and lymphocytic infiltrates of the arterial wall and perivascular tissues were the basic histological changes in the lung arteries of different diameters. All this fatal changes developed independently of the therapeutic and prophylactic anticoagulation.