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Introduction/Objective Kidney injury has now become one of the known complications following COVID-19 infection and vaccination. Only few cases of minimal change disease following administration of COVID-19 vaccination and infection have been reported. This study was to highlight incidence of minimal change disease following COVID-19 infection or vaccination. Methods/Case Report Case 1:15 year-old female with past medical history of asthma and hypercholesterolemia presented for evaluation of periorbital edema, nephrotic-range proteinuria, hypoalbuminemia, elevated serum creatinine, elevated blood pressures, and hematuria after COVID-19 infection. Renal biopsy after 1 week of infection showed unremarkable glomeruli and negative immunofluorescent stains in glomeruli, and 20-30% fusion of foot processes. The biopsy was consistent with a minimal change disease with features of natural remission (her nephrotic-range proteinuria resolved soon after). Case 2: 18 year-old female with no significant past medical history presented with a chief complaint of generalized swelling, which started around the same time she received her 1st dose of Pfizer COVID vaccine (the 2nd dose 2 months later). She had a nephrotic range proteinuria and hypoalbuminemia, but normal level of serum creatinine. A renal biopsy after 4 months of vaccination showed unremarkable glomeruli by light microscopy, negative immunofluorescent study, but diffuse effacement of foot processes involving more than 80% of the examined loops by electron microscopy. This biopsy findings were consistent with a minimal change disease. Both patients did not receive any treatment before the renal biopsies. Results (if a Case Study enter NA) NA Conclusion Minimal change disease can be a rare complication following COVID-19 infection or Pfizer COVID-19 vaccination, raising a question if there are similar antigens induced by the infection or by the vaccination that trigger the minimal change disease. Further studies are needed to determine the incidence and pathophysiology of minimal change disease either post COVID-19 vaccines or following COVID-19 infections.
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Objective: A new generation of vaccine technology platform has been developed to combat the COVID- 19 pandemic, the mRNA vaccine. The EMA granted the Pfizer- BioNTech COVID-19 vaccine an emergency use authorization in December 2020 with limited clinical experience, especially in the pediatric population. Method(s): Here, we present a case-report of a 17-yearold girl, who was vaccinated with the mRNA-COVID vaccine in October 2021, and developed a gross hematuria and proteinuria the day after the vaccination. Result(s): The patient presented at our outpatient clinic three days after the vaccination with new-onset hematuria and proteinuria. Up to this date, she had no former known medical conditions and the family history was negative regarding kidney diseases. We excluded nephrolithiasis, autoimmune glomerulonephritis and urinary tract infection as causes. The laboratory chemistry of the kidney was within normal range. The proteinuria dissolved spontaneously, and a microhematuria persisted. One day after the second dose of Cominarty in November 2021, the gross hematuria with proteinuria relapsed. A treatment with an ACE-inhibitor did not have any effect on the proteinuria. At this point, only a few casereports of patients with a comparable clinical course, especially from Japan, were published. In suspicion of a vaccine-triggered nephritis we started a prednisolon therapy which dissolved the proteinuria and induced a regression of the haematuria to a minimal stage. Conclusion(s): Within the last year, the medical community has gained more insights concerning mRNA vaccines. There is growing evidence, that mRNA vaccines can trigger de novo or relapse IgA nephropathy. But more systematic research and long-term evaluation is desirable to elucidate the underling pathophysiology as well as the influence on kidney survival of affected patients in the future. Furthermore, patient education should incorporate the risk of hematuria and proteinuria in children when applying mRNA vaccines.
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Introduction: Liver abscesses are caused by direct spread from peritonitis, biliary tract infection or via hematogenous seeding from a distant source. Most are polymicrobial, however Escherichia coli and Klebsiella pneumoniae are the most common offending pathogens. Patients usually present with pain, fever, and clinical signs of infection. We describe a case of spontaneous liver abscess in a non-toxic patient that recurred 10 years after a previous abscess. Case Description/Methods: A 73-year-old-man with a history of type 2 diabetes mellitus, hypertension, CAD status post CABG and PCI 3 years ago, and abdominal aortic aneurysm status post endovascular aneurysm repair presented with 2 weeks of dark urine. After receiving his COVID-19 booster and influenza vaccinations, he developed flu-like symptoms with a self-resolving fever of 101.8degreeF. He had dark amber urine without dysuria or hematuria. Later, he experienced generalized weakness and decreased oral intake. Outpatient labs showed elevated liver function tests, and he was told to present to the ED. On arrival, he was afebrile with stable vitals. Physical exam was unremarkable. Laboratory evaluation showed a hemoglobin of 11.7 g/dL, sodium of 133 mEq/L, creatinine of 1.4 mg/dL, aspartate aminotransferase of 117 U/L, alanine aminotransferase of 212 U/L, alkaline phosphatase of 825 U/L, total bilirubin of 4.1 mg/dL, and direct bilirubin of 2.1 mg/dL. Triple-phase CT showed a 2.8 cm mass in the right liver lobe with linear enhancement. Ultrasound showed mixed echogenicity measuring 3.6 x 2.9 x 3.3 cm in segment 8 of the liver. On further evaluation, patient had an E. coli abscess diagnosed 10 years prior, managed with antibiotics and drainage. At that time, the abscess was within the right inferior liver lobe, similar to his current abscess. LFTs downtrended. Abscess was aspirated, with culture growing oxidase negative, gramnegative rods, likely E. coli. Patient started on ceftriaxone and metronidazole, to undergo colonoscopy as an outpatient and rule out colonic bacterial translocation. Discussion(s): Pyogenic liver abscess can result in significant morbidity and mortality because of worsening infection and sepsis. Abscesses occur because of spread from adjacent infection or after recent surgeries. Recurrence is very rare. Here, we describe a very unusual case of a pyogenic liver abscess growing E. coli in a non-toxic patient, with the same location and causative organism as an abscess managed 10 years prior. (Figure Presented).
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Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow;anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl;albumin 1,9 gr/dl;cholesterol and triglycerides were high;proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved;proteinuria remained >3 gr/24 hours.Copyright © Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado. All Rights Reserved.
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Introduction: IgA vasculitis is more commonly seen in the pediatric population than in adults. Rarely IgA vasculitis is associated with malignancy, most commonly solid tumor malignancies, although there are case reports of association with hematologic malignancies. We report a case of large B-cell lymphoma mimicking IgA vasculitis in a 33-year-old immunosuppressed male with a prior history of IgA vasculitis. Case Description/Methods: A 33-year-old Caucasian male post renal transplant from reflux nephropathy on chronic immunosuppression was hospitalized for postprandial epigastric abdominal pain, nausea, vomiting and diarrhea. Two years prior, he was admitted for the same symptoms, palpable purpura of the lower extremities and elevated serum IgA. Enteroscopy had shown duodenal and jejunal ulceration with biopsies staining positive for IgA, confirming IgA vasculitis. He had complete resolution with a steroid taper. His current presentation had resulted in multiple hospital admissions, but empiric trial of steroids failed to alleviate symptoms. Vitals were normal and exam was notable for epigastric tenderness. Labs were notable for WBC 19.00 x103/cmm with normal differential, hemoglobin 9.2 gm/dL (prior 11.0 gm/dL), CRP 20.7 mg/L, serum creatinine 2.7 mg/dL (prior 1.5 mg/dL), and urinalysis with proteinuria, sterile pyuria, and hematuria. CTA abdomen/pelvis revealed thickening of the duodenum with shotty mesenteric lymph nodes without ischemia. Enteroscopy revealed an erythematous duodenum and jejunum (figure A). Jejunal biopsy (figure B) revealed CD20 positive cells consistent with DLCBL (figure C). He was seen by oncology and treated with R-CHOP but later unfortunately expired due to COVID-19 complications. Discussion(s): Non small cell lung cancer and renal cell carcinoma are most commonly associated with IgA vasculitis. It may also be seen in both Hodgkin and Non-Hodgkin lymphomas in adult patients. If IgA vasculitis occurs after a malignancy is diagnosed, it may indicate that metastasis has occurred. Malignancy associated IgA vasculitis is more likely to have an incomplete response to steroids and requires treatment of the underlying malignancy to achieve remission. Our case illustrates posterior probability error and premature closure cognitive biases. We should consider alternative diagnoses rather than anchor on prior diagnoses even when presentations are similar. Our case also highlights the importance of considering occult malignancy in adults with diagnosis of IgA vasculitis.
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Hematuria occurring in patients with acute kidney injury caused by Corona Virus Disease 2019 (COVID-19) infection has been reported. However, cases of macroscopic hematuria in COVID-19 patients leading to a severe decrease in hemoglobin have not been reported heretofore. Herein, we describe the case of a 56-year-old male patient who suffered from spontaneous prostatic hemorrhage caused by thrombocytopenia and coagulation dysfunction associated with COVID-19 infection, which manifested as macroscopic hematuria, bladder blood clot tamponade and severe hemoglobin decline. Prostatic hemorrhage was diagnosed by endoscopy. There was no recurrence of macroscopic hematuria after undergoing transurethral prostate electrocoagulation for hemostasis, infusing plasma to supplement coagulation factors and taking finasteride. One month after the bleeding event, the patient's blood routine reexamination revealed that the platelet count returned to the normal value and coagulation was normal.
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We present three cases of IgA nephropathy with gross hematuria following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination. Case 1 was a 60-year-old woman who has previously experienced transient proteinuria. Case 2 was a 22-year-old woman with no history of urinary abnormality. Finally, case 3 was a 66-year-old woman who has had microscopic hematuria since she was in her 50s. They were all diagnosed as IgA nephropathy with little histological active lesion. Their renal function and proteinuria improved without the use of corticosteroids. There were differences in the findings of vascular endothelial damage based on the time between the appearance of gross hematuria and renal biopsy. Glomerular endocapillary damage could be a part of the mechanism triggered by mRNA vaccination. When a patient presents with gross hematuria following vaccination, a comprehensive approach including renal biopsy should be considered.
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Gross hematuria after upper respiratory tract infections is a well-known characteristic symptom of immunoglobulin A nephropathy (IgAN). In recent years, there have been several reports of existing or newly diagnosed patients with IgAN susceptible to gross hematuria after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, reports of patients with IgAN and gross hematuria after SARS-CoV-2 infection are extremely rare despite a considerable number of patients with coronavirus disease 2019 (COVID-19) who preferentially present with upper respiratory symptoms. Here, we report the cases of 5 Japanese patients with IgAN who developed gross hematuria associated with SARS-CoV-2 infection. These patients presented with fever and other COVID-19-related symptoms, followed by the appearance of gross hematuria within 2 days, which lasted for 1-7 days. Acute kidney injury occurred after gross hematuria in 1 case. In all cases, microhematuria was identified before gross hematuria associated with SARS-CoV-2 infection, and it persisted after the gross hematuria episode. Because repeated gross hematuria and persistent microhematuria may lead to irreversible kidney injury, the clinical manifestations of patients with IgAN during the COVID-19 pandemic should be carefully monitored.
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Background: Since the outbreak of COVID-19, vaccination has been considered as an important measure against it. Side effects have always been an inseparable component of vaccination, which in this study, Sinopharm vaccine, its side effects and the differences of their manifestation amongst men and women have been investigated. Objective(s): This study aimed to compare the side effects of the Sinopharm vaccine among men and women working in some medical centers in Tehran, Iran. Method(s): This cross-sectional descriptive-analytical study on 890 healthcare workers of 7 medical centers in Tehran within 2 months, from late June to late August 2021. The samples were selected by the complete enumeration method, and the required data were collected using a questionnaire. Only those who received the Sinopharm vaccine at least 10 days before the study were included. Result(s): Of 890 participants, 22.96% and 77.30% were women and men, respectively, and 65.8% of women and 78.1% of men were in the age range of 20-29 years. It was revealed that 74.75% of women and 26.16% of men had at least one side effect. The incidence of at least one side effect was significantly higher in women than in men (P<0.001). It was also found that 12 side effects were significantly higher in women than in men. Most men and women had side effects within the first 24 h after vaccination. There was no significant difference in taking therapeutic measures to reduce or minimize the post-vaccination complications between men and women;however, 9.4% of men and 27.2% of women reported a decline in their ability to perform daily activities as they were unable to do their everyday tasks the day after vaccination which was significantly different between the two groups (P<0.001). Conclusion(s): The results showed that the occurrence rate of side effects after receiving the Sinopharm vaccine was significantly higher in women than in men. Moreover, women were significantly less able to perform daily routines than men.Copyright © 2022, Author(s).
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A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.
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Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023
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BACKGROUND: With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines. METHODS: A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100 000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment. RESULTS: Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100 000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100 000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR = 0.76, 95% CI 0.56-1.03; CoronaVac: IRR = 0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR = 0.92, 95% CI 0.72-1.17; CoronaVac: IRR = 0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR = 0.39. 95% CI 0.15-1.03; CoronaVac: IRR = 1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines. CONCLUSIONS: There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines.
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In coronavirus disease 2019 (COVID-19) patients, acute tubular injury is the most frequently documented kidney disease. According to the current knowledge, its cause is assumed to be multifactorial. Other kidney diseases observed in non-severely ill COVID-19 patients are thrombotic microangiopathy, necrotizing glomerulonephritis, primary podocytopathy and interstitial nephritis. Even after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, necrotizing glomerulonephritis and other kidney diseases were observed. It is recommended that a renal biopsy be performed in COVID-19 patients with elevated creatinine, proteinuria, and/or hematuria to rule out a variety of other renal disorders. Both diseases (during a SARS-CoV-2 infection and after vaccination) probably share common features that act as triggers when the patient is preconditioned for a renal disease. The activation of the complement system and the formation of neutrophil extracellular traps (NET) could play a role in the pathogenesis. As the first report on autopsies carried out on COVID-19 patients throughout Germany showed, the autopsy plays a central role for a better understanding of this (relatively) new disease.Copyright © 2022, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
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Introduction: There have been some reports on flare-ups of kidney diseases following COVID-19 vaccines such as IgA nephropathy and minimal change disease. However, there have been few reports on those of IgA vasculitis following the vaccines yet. We report a case of IgA vasculitis with a flare-up of gross hematuria and lower-limb purpura following Moderna COVID-19 vaccines. Method(s): The patient is a 16-year-old female with no previous history of abnormal results of urinalyses before April in 2021. She had developed microscopic hematuria, proteinuria and purpura on both of her lower limbs that emerged and then disappeared repeatedly since then. She received Moderna COVID-19 vaccines in August and September in 2021, both of which were followed by gross hematuria lasting for around 10 days. The lower-limb purpura reemerged at the same time as the hematuria. Microscopic hematuria of around 30-49 RBC/HPF, glomerular hematuria of moderate degree and urine protein-to-creatinine ratio (UPCR) of around 0.8 g/gCr had continuously been detected. Skin and kidney biopsies were performed in December in 2021 and in February in 2022 respectively. Result(s): The skin tissue showed formation of leukocytoclastic vasculitis, and the kidney tissue showed that of cellular and fibrocellular crescents and endocapillary hypercellularity. Immunofluorescence staining of both tissues showed deposition of galactose-deficient IgA1(Gd-IgA1) and C3, and she was diagnosed as IgA vasculitis. She received steroid pulse therapy followed by tonsillectomy. The lower-limb purpura has disappeared after she received three courses of the steroid pulse therapy, but microscopic hematuria and UPCR of around 0.8 g/gCr have still continued. Conclusion(s): IgA vasculitis is leukocytoclastic vasculitis characterized by deposition of Gd-IgA1 on microvessel walls in skin and on glomerular capillaries in kidneys. The detailed mechanism of IgA vasculitis has not been fully elucidated yet. Gross hematuria following an upper respiratory infection is considered as a characteristic clinical symptom of IgA vasculitis as well as IgA nephropathy. Post-vaccination gross hematuria of patients with IgA nephropathy has been reported, and it is believed that innate immunity is related to its mechanism. Moderna COVID-19 vaccines, which the patient received, are mRNA vaccines. We estimate that exposure to the mRNA vaccine triggered excess glomerular deposition of Gd-IgA1-containing immune complexes and subsequent gross hematuria by overactivation of innate immunity such as Toll-like receptors that detect RNA. This case suggests that such immune activation by a mRNA vaccine might be related not only to the mechanism of IgA nephropathy but also to that of IgA vasculitis. No conflict of interestCopyright © 2023
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Immunoglobulin A (IgA) nephropathy is the most common type of glomerulonephritis worldwide characterized by excessive serum levels of glycosylated which triggers the generation of glycan-specific IgG and IgA autoantibodies. This pathological condition results in the formation of circulatory IgA immune complexes, which are essential for the development of glomerular inflammation, especially IgA nephropathy. The serum galactosylated IgA1, IgG, and IgA autoantibodies are suggested as the biomarkers of IgA nephropathy since IgA antibodies are early markers for disease activity too. Serum IgA antibodies emerged as the early COVID-19-specific antibody response about two days after initial symptoms of COVID-19 in comparison with IgG and IgM antibody concentrations, which appeared after five days. IgA nephropathy is frequently presented as microscopic or macroscopic hematuria and proteinuria with a male predominance. COVID-19 infection can include several organs aside from the lungs, such as kidneys through different mechanisms. It is demonstrated in most cases that short-lasting symptoms such as gross hematuria resolve either spontaneously or following a short course of steroids. This review summarized the reported cases of relapses or denovo reported cases of relapses or de-novo IgA nephropathy and IgA vasculitis following COVID-19 vaccination.Copyright © 2023 The Author(s);Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Introduction: Patients with chronic kidney disease (CKD) and that have SARS-CoV-2 infection are at higher risk of developing acute kidney injury (AKI) and have higher mortality rates after hospital admission. Method(s): The study group included 120 patients: 70 with a history of CKD (eGFR rate of <60 mL/min);and 50 were within the control group with no history of kidney disease. Data on patients' gender, age, co-morbidities, and laboratory results from blood and urine samples, taken at admission into the ER, were collected. Laboratory values included calculated eGFR (by the CKD-EPI 2021 formula), highly sensitive inflammatory markers, D-dimer, blood-cell counts, and changes in urine parameters (hematuria, proteinuria). Co-morbidities included hypertension, obesity, diabetes mellitus, vascular disease, and CKD. All patients had been treated by the official protocol of the Republic of Bulgaria for SARS-CoV-2 treatment, but not all of them have received remdesivir. We also assessed which risk factors may have led to AKI with emphasis to the levels of specific biomarkers (IL-6, IL-18, KIM-1, NGAL, ACE2, SAA). Result(s): Overall median age of patients was 65.7 years;gender ratio was 50% M/F in both groups. Median duration of symptoms before hospitalization was 6 days. Of the 120 patients, 35% were febrile with temperatures >38oC Overall, creatinine level on admission was elevated in 58.3% of cases;eGFR was <60 mL/min/1.73 m2 in 50% of patients. Mean value of eGFR on admission was 82.3 mL/min/1.73 m2 for the non-CKD group and 49.5 mL/min/1.73 m2 for the CKD group. In total, three patients needed renal-replacement therapy: two patients from the CKD group and one from the non-CKD group. Urine samples showed 39 patients had proteinuria: of these, 87.1% had 1+ proteinuria and the others had >1+. Of the 22 cases of hematuria, 54.5% had only 1+ hematuria. Acute kidney injury occurred in 38 patients (31.6%) of whom 31 had CKD (44.3% of CKD patients). Overall, within our cohort of 120 patients, in-hospital mortality was 19.1% (23 patients): of these, 66.6% had AKI (19 patients). Overall, 100% of patients that did not survive Covid-19 also had CKD. We also analyzed risk factors that may have led to AKI. Logistic regression for risk factors for AKI showed that, the factors significantly linked with the incidence of AKI were an eGFR of >=60 mL/min/1.73m2, having symptoms for >=6 or more days before hospitalization, and not having received remdesivir as a treatment. Also, the levels of IL-6, SAA, and KIM-1 were significantly higher for patients that had AKI. Conclusion(s): We found that CKD was not a risk factor for COVID-19-related AKI. Conversely, we found that developing AKI was significantly associated with in-hospitalization death, which was linked with renal inflammatory processes and injury caused by SARS-CoV-2. No conflict of interestCopyright © 2023
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Introduction: Acquired haemophilia A (AHA), characterized by neutralizing autoantibodies against factor VIII (FVIII), is a rare disorder (1.5/million/y). Pregnancy-relatedAHAis an even rarer disorder affecting 0.03/million/y with an incidence of 1 case/350000 births. Aim(s): to describe two pregnancy-related AHA presented at the same year of 2022. Method(s): We evaluate data from two women (patient 1 and 2) with AHA diagnosed within 1 year following childbirth. Result(s): Two women, patient 1 (P1) and P2 with 32 and 33-year old respectively, presented AHA seven (P1) and six (P2) months after delivery. They had no relevant medical history, except for COVID-19 vaccination fifteen days before the development of bleeding in P1, and late-pregnancy COVID-19 infection in P2. They had no complications related to childbirth. The bleeding events in both patients were haematuria and apparently spontaneous hematomas in the upper limb, requiring no haemostatic treatment. Laboratorial investigation, demonstrated in P1 a FVIII activity of 0.026 IU/ml and a FVIII antibody titer of 26 Bethesda Units (BU), and in P2 a FVIII activity of 0.005 IU/ml and a FVIII antibody titer of 34 BU. Concomitant disorders were excluded. The patients started eradication of the inhibitors with prednisone (1mg/kg/day orally). In P1, inhibitor titer was 0 BU and FVIII> 0.5 IU/ml after 8 weeks of immunosuppression. During eradication period, the P2 had a hematoma in right thigh treated with bypassing agent (FEIBA), but the inhibitor titer was 0 BU and FVIII>0.5 IU/ml after 1 month of inhibitor eradication. Curiously, P2 with FVIII< 0.01 IU/ml and a higher inhibitor titer than P1 had a faster response to prednisolone therapy (4 vs. 8 weeks). Currently, prednisone has been completely withdrawn in P1 and the prednisone dosage is being gradually reduced in P2. Discussion/Conclusion: Data from these two women with pregnancyrelated AHA are similar to previously described cases and expand the knowledge about this rare disorder. The peculiarity of this report is due to the emergence of two cases of a disease with markedly low incidence, in the same local and year, raising the question of whether there were new acquired factors (as immunological triggers such as COVID-19 infection or vaccination) that could be involved in the modification of the natural history of the disease. It cannot be excluded the possibility that these two cases were a coincidence.
ABSTRACT
Background/Introduction: Thromboinflammation in severe COVID-19 is associated with disease severity and outcome. The kallikrein pathway is suggested to mediate thromboinflammation in COVID-19 by activating inflammatory pathways and contactmediated coagulation. Purpose(s): The DAWn-antico study investigates if a multitarget modulation of the thromboinflammatory response improves outcomes in hospitalized patients with severe COVID-19. Method(s): In this multicenter open-label randomized clinical trial (EudraCT 2020-001739-28), patients hospitalized with COVID- 19 were 1:2 randomized to receive standard of care (SOC) or SOC plus study intervention. The intervention consisted of aprotinin (2,000,000 IE IV four times daily) combined with low-molecular-weight heparin (LMWH;SC 50 IU/kg twice daily at the ward, 75 IU/kg twice daily at intensive care). Additionally, patients with predefined hyperinflammation received the interleukin-1- receptor antagonist anakinra (100mg IV four times daily). The primary outcome was time to a sustained 2-point improvement on the 7-point WHO ordinal scale for clinical status, or discharge. The trial was funded by Life Sciences Research Partners, Research Foundation Flanders (G0G4720N), and KU Leuven COVID-19 fund. Result(s): Between 24 June 2020 and 01 February 2021, 105 patients were randomized, and 102 patients were included in the full analysis set (intervention N=67 vs. SOC N=35). Twenty-five patients from the intervention group (37%) received anakinra. The intervention did not affect the primary outcome (HR 0.77 [CI 0.50;1.19], p=0.24) or mortality (intervention n=3 (4.6%) vs. SOC n=2 (5.7%), HR 0.82, [CI 0.14;4.94], p=0.83). There was one treatment-related adverse event in the intervention group (hematuria, 1.49%). There was one thrombotic event in the intervention group (1.49%) and one in the SOC group (2.86%), but no major bleedings. Conclusion(s): In hospitalized COVID-19 patients, modulation of thromboinflammation with high-dose aprotinin and LMWH with or without anakinra did not improve outcome in patients with moderate to severe COVID-19. (Disclosure: this RCT was presented at ISTH 2022 in London and will be published in Research and Practise in Thrombosis and Haemostasis).