Two synchronous primary mesenteric neuroendocrine tumors in a patient: a case report.

Primary mesenteric neuroendocrine tumors represent a rare clinical entity, challenging to manage, while a combination of imaging is demanded in order to differentiate it from metastatic disease, and set the diagnosis. If the tumor is resectable, surgery is the fundament of the therapeutic approach. The appearance of a second primary mesenteric tumor suggests an unacquainted scenario. The current article presents a case of a 40-year-old woman, who underwent laparoscopic excision of a mesenteric tumor located close to the left pararenal space. Pathology with immunohistochemistry examination reported neuroendocrine tumor grade 2. No further treatment was necessary. Seven months later, 68-Gallium DOTATATE detected another primary neuroendocrine tumor located at the right retroperitoneal space without other lesions. The second tumor was also resected laparoscopically, and the pathology confirmed the diagnosis of another neuroendocrine tumor G2. The postoperative course was uneventful, and six months later the patient is disease-free. The adequacy of 68-Gallium DOTATATE for the preoperative diagnosis of primary mesenteric tumors, the role of the laparoscopic approach, and the extent of lymph node resection are matters addressed in this article.

The prognostic value of two histopathologic classification models of ANCA-associated glomerulonephritis: a prospective study.

BACKGROUND: Berden Classification and anti-neutrophil cytoplasmic antibody (ANCA) Renal Risk Score are classification models for rating renal histology and predicting outcome in patients with ANCA-associated Vasculitis/Glomerulonephritis (AAV/GN). In the present study we compare their ability to predict renal function outcome in short- and long-term follow up. METHODS: Patients with an initial diagnosis of AAV/GN based on kidney biopsy were classified according to Berden and Renal Risk Score, started on the same treatment protocol, and were followed prospectively for up to 60 months. Renal function was recorded at 3mo(T3), 6mo(T6) and 60mo(T60), and results were compared to both classification systems. RESULTS: Ninety four AAV/GN patients, M/F = 36/58, age = 60.05 (18-82)yrs were included. Based on Berden classification, patients grouped as Focal (n = 24), Crescentic (n = 35), Mixed (n = 21) and Sclerotic (n = 14), had significant differences in estimated glomerular filtration rate (eGFR) only at T3, while the percentage of those requiring hemodialysis differed at T0, T3, T6 but not at T60. According to the Renal Risk Score, patients were classified as Low (n = 8), Medium (n = 47) and High (n = 39) risk, and showed significant differences in both eGFR levels, proportion of hemodialysis, at T0, T3, T6 and end-stage kidney disease (ESKD) at T60. Even patients classified as Mixed (Berden) and as Medium or High risk (Renal Risk Score) had significant improvement from T0 to T6. Relapse could not be predicted by either system. CONCLUSION: Both methods were able to predict short-term renal function outcome and need for hemodialysis, but the Renal Risk Score showed significant superiority in predicting renal function outcome and ESKD after long-term follow up.

The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats.

Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann-Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.

Dermatoscopic shiny white structures in benign cutaneous tumours.

The dermatoscopic characteristics of shiny white structures (SWS) in malignant skin tumours are well described, but data on benign skin neoplasms are scarce. To evaluate dermatoscopic features of SWS in common benign tumours, we reviewed our database for histopathologically confirmed cases. The dermatoscopic images were evaluated for the presence of any type of SWS. Those images with SWS were further analyzed for their quantity, distribution and shape. Of 2420 evaluated benign tumours, 357 (14.8%) displayed SWS. The highest frequencies were observed in pyogenic granuloma (62/100, 62.0%), angioma (63/113, 55.8%) and adnexal tumours (42/84, 50.0%). The lowest frequency was found in common nevi (16/1032, 1.6%) and solar lentigo (0%). The presence of SWS was not associated with sex or anatomic location. SWS were usually diffuse and multiple. SWS may be present in a broad spectrum of benign tumours. Therefore, they should not be considered as de-facto indicators of malignancy.

Cutaneous lesions in a COVID-19 patient leading to a surprising diagnosis.

Differential diagnosis of skin lesions is broad. Cutaneous metastases should always be considered in the appropriate clinical and laboratory context to ensure accurate diagnosis. https://bit.ly/400Msre.

A patient with dialysis-dependent acute kidney injury due to hantavirus complicated with SARS-CoV-2 infection.

In this case, we report a 64-year-old man presenting with anorexia, nausea and vomiting, mild abdominal pain, and oligoanuria for a few hours. His previous medical history included diabetes, hypertension, and chronic kidney disease (CKD) stage 3. Upon arrival, laboratory results revealed stage III acute kidney injury (AKI) with hyperkalemia requiring dialysis treatment. During hospitalization, both pre-renal and post-renal causes of AKI were excluded, and a careful diagnostic evaluation, including kidney biopsy and serology testing, revealed acute interstitial nephritis and positive IgM for hantavirus. The patient was started on steroid treatment, which led to complete recovery of kidney function over 3 months. Moreover, during his hospitalization, the patient was also diagnosed with SARS-CoV-2 infection, possibly due to intra-hospital transmission and was hospitalized at the COVID-19 Department for 14 days, eventually with no further complications. Hantavirus nephropathy should be at the differential diagnosis of AKI, even in the absence of typical symptoms. Steroid treatment may be helpful in reversal of kidney injury.

ANCA-Associated Vasculitis May Result as a Complication to Both SARS-CoV-2 Infection and Vaccination.

In the last two years, our world experienced one of the most devastating and fast-exploding pandemic, due to the wide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The scientific community managed to develop effective vaccines, the main weapons to shield the immune system and protect people. Nevertheless, both SARS-CoV-2 infection and the vaccination against it have been associated with the stimulation of inflammatory cells such as T and B lymphocytes that results in a cytokine storm, endothelial inflammation and vascular injury, which can lead to different types of vasculitis. We present the first case of de novo MPO-ANCA-associated vasculitis, which developed shortly after SARS-CoV-2 vaccination, adequately responded to treatment, and subsequently relapsed after COVID-19 infection. With this case, we indicate an etiological connection between viral infection and disease development, as well as the possibility of a common immune mechanism between SARS-CoV-2 infection and vaccination, that can stimulate vascular events and lead to vasculitis. There have been several case reports of de novo vasculitis, affecting large, medium, or small vessels, following either infection or vaccination against COVID-19, during the pandemic outbreak. We summarize previous reports and also analyze proposed pathogenic mechanisms between SARS-CoV-2 and vasculitis.

CYLD expression in endometrial carcinoma and correlation with clinicohistopathological parameters.

OBJECTIVE: Endometrial cancer is a threat to women health worldwide. Cylindromatosis (CYLD) enzyme is a tumour suppressor, considered an effective prognostic marker in various malignancies, but its role in endometrial carcinoma is not fully elucidated. Here, we sought to estimate the prognostic value of CYLD expression in endometrial carcinoma. MATERIALS AND METHODS: CYLD levels were immunohistochemically evaluated in 65 patients with endometrial carcinoma and inferential statistics were applied. RESULTS: Low or negative CYLD expression significantly correlates with older ages, non-endometrioid and invasive carcinomas, tumours with moderate or poor differentiation and advanced stages. Moreover, non-endometrioid and invasive carcinomas are independent risk factors for weaker CYLD expression. Kaplan-Meier analysis illustrated that negative or low CYLD expression is statistically significantly associated with increased death risk, compared to moderate or high expression. CONCLUSION: This study demonstrates for the first time a clear correlation between CYLD expression and clinicohistopathological parameters of endometrial carcinoma patients, suggesting its use as a potential prognostic/predictive marker for Endometrial Carcinoma.

De novo Minimal Change Disease in an Adolescent after Pfizer-BioNTech COVID-19 Vaccination: A Case Report.

This is the first report in an adolescent of minimal change disease (MCD) after the first injection of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) with complete remission following steroid treatment. An 18-year-old white male with no prior medical history complained of gastrointestinal symptoms 11 days after his vaccination. Ascites and lower extremity edema were observed a few days later. He was admitted to a hospital as laboratory testing revealed proteinuria of 10.5 g/24 h, normal creatinine levels, and serum albumin of 1.8 g/dL, confirming the presence of nephrotic syndrome. Immunology and serology tests were unremarkable. A diagnostic kidney biopsy showed no significant glomerular or tubular abnormalities in light microscopy with negative immunofluorescence. Treatment with methylprednisolone 48 mg daily was initiated. A week after discharge, proteinuria declined to 1.2 g/24 h, and edema had disappeared, and 6 weeks later, complete remission was evident. As COVID-19 vaccination has been associated with the development of de novo and relapsing MCD, and this case provides additional support for this possible correlation.

Preoperative Hyponatremia Indicates Complicated Acute Appendicitis.

Introduction: Acute appendicitis is the most common surgical emergency. Early detection of patients with complicated appendicitis leads to prompt surgical management and better outcome. This study investigated the relationship between the severity of acute appendicitis and the presence of preoperative hyponatremia. Materials and Methods: We retrospectively reviewed the medical files of adult patients operated on for acute appendicitis over a 6-year period. Hyponatremia was defined as serum sodium level of ≤135 mEq/L. Patients were classified into complicated appendicitis and noncomplicated appendicitis according to operative findings and/or histopathology reports. Results: A total of 129 patients were identified and included in this study. Complicated appendicitis was found more frequently in female patients and older patients. Hyponatremia was found significantly more frequently in patients with complicated appendicitis (p < 0.001) and also in patients with perforation than without perforation (p=0.047). Conclusions: The present study demonstrated that preoperative hyponatremia is associated with complicated appendicitis. Serum sodium levels, a routine, low-cost laboratory test, could act as an accessory marker aiding surgeons in earlier identification of gangrenous or perforated acute appendicitis.

The Impact of COVID-19 on the Training of Surgical Residents in Greece: Results of a Survey Conducted One Year after the Onset of the Pandemic.

Background: The coronavirus disease (COVID-19) pandemic is an ongoing crisis. In light of mounting concerns about the training of surgical residents, we examined surgical residents perceptions regarding the pandemic's impact on their training. Methods: We developed an anonymous online questionnaire comprising 15 multiple-choice questions, which we sent via email to residents educated and employed in northern Greece hospitals. Our survey took place in January and February of 2021. Results: A total of 124 residents across a broad spectrum of surgical fields completed the questionnaire. The majority (51.6%) reported a significant decline in the number of operations performed weekly during the pandemic. Approximately 38% of the respondents stated that their surgical skills have been negatively affected to a significant extent, and 35.5% reported that their theoretical knowledge had deteriorated to a moderate extent. Almost half of them reported that they were satisfied with the online courses and a total of 67.7% affirmed the need to prolong their clinical training. Conclusions: The aims and scope of a surgical department include the provision of high-quality training to young surgeons. The impact of the pandemic on routine surgical activities has been dramatic. Our results clearly indicate that young surgeons have been significantly affected in terms of their training.

How to spot a basosquamous carcinoma: a study on demographics, clinical-dermatoscopic features and histopathological correlations.

Basosquamous carcinoma (BSC) is a relatively rare type of neoplasm originating from basal cell carcinoma with features of squamous differentiation. BSC has an aggressive local behaviour with a tendency for recurrence and a less frequent metastatic potential The primary objective was to describe the dermatoscopic features of the tumour. Secondary goals were to detect the morphological features of the tumour along with patients' characteristics and to evaluate possible dermatoscopic and histopathological correlations Twenty-two patients with 25 BSCs were enrolled. All tumours were surgically excised and diagnosis was based on histopathology. Clinical and dermatoscopic images were evaluated by two investigators based on pre-defined criteria, and a statistical analysis was performed The median age of the patients was 78 years old (range: 52-88) and the male/female ratio was 2.14. All patients reported history of either occupational (50%) or recreational (50%) intensive sun exposure and 72.73% had signs of actinic keratosis. The most common anatomical site of the tumours was the head/neck area (72%). Clinically, nodular (64%), ulcerated (88%) and non-pigmented (76%) lesions prevailed. Dermatoscopically, 92% had prominent vasculature and monomorphous arborizing vessels with a diffuse arrangement, representing the most frequently observed type. Ulceration (88%), SCC dermatoscopic criteria (56%), white strands/blotches (56%) and features of pigmentation (40%) were also detected We suggest that the most common prototype of BSC is an ulcerated, facial nodule in elderly males with photo-damaged skin, dermatoscopically displaying combined features of mostly nodular BCC and, to a less extent, SCC.

Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease.

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p < 0.0001, and, with intima-media thickness (IMT), the severity of RANKL expression R2 = 0.3, p < 0.0001. Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall.

Non-Operative Management of Delayed Splenic Rupture 4 Months Following Blunt Abdominal Trauma.

BACKGROUND Delayed splenic rupture is a rare complication of non-operative management of a primary splenic trauma which, without proper clinical vigilance, may result in life-threatening events. It usually occurs 4-8 days after injury and, in most cases, surgery is the treatment of choice. Since non-operative management of splenic trauma, which allows splenic salvage, has become increasingly popular, the same approach could also be applied in delayed splenic rupture. We herein present a case of delayed splenic rupture that occurred 4 months after the trauma and was successfully managed non-operatively. CASE REPORT A 32-year-old woman presented with diffuse abdominal pain, chest pain, and dyspnea 4 months after sustaining minor thoracoabdominal blunt trauma due to a car accident. That event was inadequately investigated and was not admitted for further monitoring. Computerized tomography revealed a rupture of a splenic hematoma in the context of the previous splenic trauma. She was closely monitored and remained hemodynamically stable. She was discharged and followed up, with no reported relapse of her clinical condition. CONCLUSIONS Delayed splenic rupture occurring 4 months after the primary splenic trauma is extremely rare. Due to its prolonged delay, delayed rupture of the spleen can easily be overlooked and not be included in the original differential diagnosis. Negligence of this event can result in dreaded complications with hemodynamic instability or even death. Furthermore, its higher mortality rate compared to primary splenic rupture highlights the importance of proper clinical vigilance. Non-operative management should be attempted in hemodynamically stable patients.

Robot-Assisted Thyroidectomy Versus Open Thyroidectomy in the Treatment of Well Differentiated Thyroid Carcinoma.

BACKGROUND: The incidence of thyroid cancer has increased worldwide during the last decade, becoming the most common endocrine malignancy and accounting for 3.8% of new cancer diagnosis. Surgical resection, namely conventional thyroidectomy, remains at the frontline of therapy, as surgical outcomes are undoubtedly successful. Minimally invasive techniques gained popularity through the years, in terms of feasibility, safety, and cosmesis. However, endoscopic approach could be characterized by some limitations concerning thyroid surgery. Robotic technology with its unique features was introduced to overcome these limitations. Since then, robotic thyroidectomy has been used for both benign and malignant thyroid disease. DATABASE: This study presents the use of robot-assisted transaxillary thyroidectomy in well-differentiated thyroid carcinoma through an extensive review of the literature in the PubMed database, including previous meta-analyses and case series. CONCLUSION: In terms of oncological efficacy, morbidity, and quality of life, outcomes seem comparable in thyroid cancer patients undergoing either open or robotic thyroidectomy. Surgical completeness also appears similar. Moreover, the rates of locoregional recurrence and survival outcome at 5 years are similar between the former and the latter, thus confirming the oncological value of robotic thyroidectomy for differentiated thyroid cancer. In order for more surgeons to adopt robotic approaches several issues need to be resolved, namely: expansion of robotic thyroidectomy in treating larger well-differentiated carcinomas and neck dissection, equipment costs, and prolonged operation times.

Undiagnosed Endoscopy Capsule Retention Causing Delayed Intestinal Obstruction in a Patient with a Small Bowel Neuroendocrine Tumor.

BACKGROUND Capsule endoscopy has played a significant role in small bowel investigation, providing the opportunity of detecting neoplastic lesions to a greater degree and at an earlier stage than other diagnostic procedures. Failure to excrete the capsule with the feces within 48 h can lead to capsule retention with increased risk of further complications such as bowel obstruction and perforation. Capsule retention can remain undetected in case of incomplete follow-up and poor patient compliance. Acute small bowel obstruction as late as many months following capsule endoscopy investigation is very rare, with only a few cases reported in the published literature. We herein report a rare case of prolonged capsule retention which remained undiagnosed, resulting in small bowel obstruction 6 months after the initial investigation. CASE REPORT An 82-year-old woman presented with abdominal pain and symptoms suggestive of intestinal obstruction. The patient history included a capsule endoscopy investigation because of episodes of abdominal pain 6 months prior to admission. Both the outcome of the investigation and the excretion of the capsule remained undetermined due to her history of dementia and follow-up failure. Radiologic investigations identified the capsule causing small bowel obstruction. Upon surgery, the capsule was found to be impacted in a stenotic small bowel lesion, and a segmental small bowel resection was performed. Histologic examination revealed the presence of a stenotic small bowel neuroendocrine tumor. CONCLUSIONS Appropriate follow-up is necessary to diagnose the complication of capsule retention which, if it remains unrecognized, can cause life-threatening complications as late as many months after capsule endoscopy.

Perioperative Antibiotic Prophylaxis: An Educative Intervention Significantly Increases Compliance.

BACKGROUND: Implementation of guidelines in daily clinical practice is often suboptimal, mainly due to doctors' poor compliance with them. Perioperative antibiotic prophylaxis (PAP) is many times administered in patients undergoing elective surgery without proper indication or for longer time than needed. Aim of this study is to investigate the effect of a simple intervention on the compliance of the medical staff with the American Society of Health-System Pharmacists (ASHP) guidelines concerning PAP administration. METHODS: A prospective 3-month audit took place including routine surgical procedures (laparoscopic cholecystectomy, inguinal hernia repair and thyroidectomy). An intervention aiming to educate the medical staff was implemented. The intervention included the demonstration of a poster and the training of the medical staff over the guidelines. A re-audit recorded the changes in daily clinical practice. RESULTS: The compliance rate regarding the number of PAP doses significantly increased from 0% before the intervention to 68.8% after the intervention for hernia repair and to 53.1% for laparoscopic cholecystectomy. The adherence rate in thyroidectomies increased from 25% to 50%, but without statistical significance. No significant difference was found for other parameters of PAP administration, namely the type of antibiotic used and the timing of the dose administration. Regarding secondary outcomes, hospitalization days were reduced, and cost of antibiotics was significantly decreased (P < 0.05). CONCLUSIONS: A simple intervention intending to educate the medical staff was successful in achieving significant improvement on the compliance rate with the PAP guidelines, highlighting the importance of promoting adherence to the already existing, well-established guidelines.

Different Types of ANCA Determine Different Clinical Phenotypes and Outcome in ANCA-Associated Vasculitis (AAV).

AIM: Accumulating evidence supports the use of antineutrophil cytoplasmic antibody (ANCA) type to classify different clinical entities. We aimed to evaluate whether the presence and type of ANCA determine different diseases, based on clinical phenotypes, renal involvement, and response to treatment. PATIENTS AND METHODS: Differences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction of estimated glomerular filtration rate (eGFR) ≥ 50%. RESULTS: A total of 92 patients (M/F 39/53, mean age 59.1 ± 15 years) diagnosed with FNGN due to ANCA-associated vasculitis (AAV), 36 (39.1%) patients diagnosed with PR3-ANCA, 39 (42.4%) patients diagnosed with MPO-ANCA, and 17 (18.5%) patients diagnosed with ANCA(-) were included. Number of involved systems differed significantly between PR3-, MPO-ANCA, and ANCA(-), with only renal involvement in 3, 25.5, and 29% of patients, two systems involved in 33, 31, and 59% of patients, and > 3 systems involved in 64, 43.5, and 12% of patients, respectively (p = 0.002). Histology classification revealed focal, crescentic, mixed, and sclerotic type in 14, 64, 19, and 3% of PR3-ANCA(+), 8, 28, 18, and 46% of MPO-ANCA, and 41, 29, 6, and 24% of ANCA(-), respectively (p < 0.0001). Primary end point of ESRD ± Death was reached in 11 (30.6%), 16 (41%), and 6 (35.5%) patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), respectively (p = NS); similarly, ESRD± > 50% eGFR reduction in 8 (22.2%), 15 (38.5%), and 5 (29.4%) patients, respectively (p = NS), meaning that patients with MPO-ANCA(+) showed a propensity to decline renal function. Rate of relapse was increased in the presence of patients with PR3-ANCA(+), 14 (38.9%), 4 (11.8%), and 2 (10.3%) of patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), had at least one relapse during the two-year follow-up (p = 0.006). CONCLUSION: Clinical phenotype and renal histology differ significantly between PR3-ANCA(+), MPO-ANCA(+), and ANCA(-) disease and FNGN; however, renal function outcome is similar, despite the increased rate of relapses in patients with PR3-ANCA(+).

Systemic complement activation in anti-neutrophil cytoplasmic antibody-associated vasculitis and necrotizing glomerulonephritis.

AIM: Due to the accumulating evidence of complement activation in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), we decided to investigate the possibility of systemic complement activation in patients with Necrotizing Glomerulonephritis secondary to AAV. METHODS: Clinical, laboratory and histological findings, and serum levels of complement components, C3a, C5a and Bb fragment of Factor B and C4d, were estimated in patients with AAV and glomerulonephritis, at time of diagnosis, before any treatment had been applied. All patients were treated with the same immunosuppressive protocol and followed up for total 24 months. Twenty age and sex matched healthy individuals served as controls. RESULTS: Serum levels of all complement components were significantly increased in patients, compared to controls; C5a: 19.9(0.02-48) vs 9.06(2.1-16.3)pg/mL, P = .002, Bb: 7.3(0.02-31.4) vs 0.2(0.02-1.6)pg/mL, P < .0001, C3a: 4.7(0.4-7.2) vs 2.4(1.09-5)pg/mL, P = .05 and C4d: 11.6(0.07-70) vs 0.7(0.07-8.2)pg/mL, P = .001, respectively. There was strong correlation between serum Bb levels and eGFR and FFS2009 score at time of diagnosis (r = -.41, P = .002 and r = .41, P = .003 respectively). Also, serum Bb levels were increased in patients with severe interstitial infiltration (P = .04) and focal necrosis (P = .01) on renal biopsy. Serum Bb levels could also predict renal function outcome during the acute phase of disease, but not at the end of follow up. CONCLUSION: We provided strong evidence of systemic activation of complement alternative pathway in the development and progression of AAV and glomerulonephritis. Serum Bb seem to play a critical role in the induction, also predicting disease activity and outcome, yet activation of classical pathway cannot be excluded.