Episodes Of Edema Research Articles

Corticosteroid therapy for nephrotic syndrome in children.

In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However about 70% of children experience a relapsing course with recurrent episodes of oedema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 - July 2002) and EMBASE (1980 - July 2002) without language restriction, reference lists of articles, abstracts from conference proceedings and contact with known investigators in the area. Randomised controlled trials were included if they were carried out in children (aged three months to 18 years) in their initial or subsequent episode of SSNS, if they compared different durations, total doses or other dose strategies using prednisone or other corticosteroid agent and if they had outcome data at six months or more. Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality and extracted data. The principle outcome measure was the number of children with and without relapse after six and 12-24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk (RR), risk difference (RD)) after testing for heterogeneity. Meta-regression was used to explore potential between-study differences due to the baseline risk of relapse, study quality and types of interventions used. Nineteen trials have been included in this review. A meta-analysis of six trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 - 24 months (RR 0.70; 95% CI 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR = 1.26 - 0.112 duration; r(2) = 0.56; p = 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR 0.44; 95% CI 0.25 to 0.78). Children in their first episode of SSNS should be treated for at least three months with an increase in benefit being demonstrated for up to seven months of treatment. In a population with a baseline risk for relapse following the first episode of 60% with two months of prednisone, daily prednisone for four weeks followed by alternate day therapy for six months would be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.

Femoro-axillary versus femoro-femoral veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock: A monocentric retrospective study.

For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF. Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis. VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest (n = 77 (14%)) and those supported by multiple VA-ECMO (n = 92, (17%)) were excluded. Out of the 333 patients studied (n = 209 Vf-Aa; n = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, n = 109), dilated cardiomyopathy (20%, n = 66), post-cardiac transplantation (15%, n = 50), acute myocardial infarction (14%, n = 46) and other etiologies (18%, n = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% (n = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation. Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation.

Patients with Steroid Sensitive Nephrotic Syndrome: A Case Series

Nephrotic syndrome (NS) is one of the most common kidney diseases found in childhood. The prevalence of nephrotic syndrome worldwide is approximately 16 cases per 100,000 children with an incidence of two to seven per 100,000 children. Nephrotic syndrome may affect adults and children of both genders and any race. Nephrotic syndrome in children can be classified into three groups; secondary, congenital, infantile, and idiopathic. In first case, a 3-year-old male patient was presented with complaints of fever, cough for 6 days and swelling all over the body, decreased urine output, oral intake for 2 days, edema of face, body and tiredness for 3 days. Laboratory investigations showed elevated ESR, ferritin and lipid profile. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis conveyed right basal pleural effusion. In second case, a 4-year-old male patient was presented with complaints of facial puffiness, fever, breathing difficulty, abdominal distension and pain but no edema. He had history of right inguinal hernia and atrial septal defect. Cholesterol level was found to be elevated. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis showed mild ascites and right pleural effusion. Presenting third case, a 12-year-old female patient was presented with complaints of edema and decreased urine output. Patient had history of recurrent episodes of edema and decreased urine output for 11 months. Laboratory investigations showed elevated total cholesterol, declined LFT test and RFT test was found to be normal. Urine routine examination showed elevated urine albumin levels (+++), pus cells, RBC, granular cast and bacteria present. USG abdomen and pelvis indicate acute glomerulo nephritis and acute to moderate ascites. Here case series with 3 cases showed the sequence of nephrotic syndrome which is treated with corticosteroid with its side effects and cumulative dose of steroid in children. Keywords: Nephrotic syndrome, Hypocholesteremia, Hypoproteinuria, Hyponatremia, pediatric

Exploring disease-specific metabolite signatures in hereditary angioedema patients.

Hereditary angioedema (HAE) is a rare, life-threatening autosomal dominant genetic disorder caused by a deficient and/or dysfunctional C1 esterase inhibitor (C1-INH) (type 1 and type 2) leading to recurrent episodes of edema. This study aims to explore HAE patients' metabolomic profiles and identify novel potential diagnostic biomarkers for HAE. The study also examined distinguishing HAE from idiopathic angioedema (AE). Blood plasma samples from 10 HAE (types 1/2) patients, 15 patients with idiopathic AE, and 20 healthy controls were collected in Latvia and analyzed using LC-MS based targeted metabolomics workflow. T-test and fold change calculation were used to identify metabolites with significant differences between diseases and control groups. ROC analysis was performed to evaluate metabolite based classification model. A total of 33 metabolites were detected and quantified. The results showed that isovalerylcarnitine, cystine, and hydroxyproline were the most significantly altered metabolites between the disease and control groups. Aspartic acid was identified as a significant metabolite that could differentiate between HAE and idiopathic AE. The mathematical combination of metabolites (hydroxyproline * cystine)/(creatinine * isovalerylcarnitine) was identified as the diagnosis signature for HAE. Furthermore, glycine/asparagine ratio could differentiate between HAE and idiopathic AE. Our study identified isovalerylcarnitine, cystine, and hydroxyproline as potential biomarkers for HAE diagnosis. Identifying new biomarkers may offer enhanced prospects for accurate, timely, and economical diagnosis of HAE, as well as tailored treatment selection for optimal patient care.

Recurrent unilateral corneal edema in a 54-year-old patient after endurance sports in low temperature

Introduction: Corneal edema in endurance sports at low temperatures is a rare occurrence, and few reports can be found in the literature. Patient and Clinical Findings: A case of unilateral corneal edema in a 54-year-old man with a history of laser in situ keratomileusis surgery, cataract surgery, and vitrectomy is presented. Recurrent episodes of corneal edema were observed during endurance cycling in temperatures below 10 °C, with complete recovery observed the next day without any treatment. Diagnosis, Interventions, and Outcomes: Pathophysiology and therapeutic strategies were discussed. Local administration of hyperosmolar saline lacked of any effect as did administration of acetazolamide. A protection of the affected eye by contact lens was not successful, but ski goggles could effectively prevent the corneal edema. Conclusions: Some single reports in the literature described roughly similar corneal findings under different conditions. A systematic evaluation of this case could reveal a fateful combination of cold temperature, physical activity, and susceptibility of the corneal endothelium. Protection from cold wind by ski goggles was found to be an effective practical approach.

Hereditary angioedema: A case report

Angioneurotic edema (ANE) is a frequently encountered presentation in the emergency department. This condition manifests itself as sudden, unpredictable episodes of edema in cutaneous and mucosal tissues, commonly affecting the eyes, oral cavity, lips, and larynx. It is crucial to acknowledge that ANE is a component of a range of allergic manifestations, often associated with urticaria and occasionally of non-allergic origin. In some cases, this condition can lead to laryngeal edema, causing airway obstruction and potentially fatal consequences if not diagnosed in a timely manner. After 2007, the term ANE was replaced by the term angioedema (AE) in the literature for its conciseness and wider recognition. The purpose of this comprehensive article is to present a detailed analysis of a clinical case involving a 75-year-old patient diagnosed with AE, accompanied by a thorough examination of relevant literature that has significantly contributed to our understanding of this complex medical condition.

À propos d’un cas pédiatrique d’allergie au kaki

Food allergy to persimmon (Diospyros kaki) is exceedingly rare. We report a case involving a 3.33-year-old child who experienced an episode of palpebral edema with pruritus and facial erythema following the first ingestion of this fruit. Allergological investigation reveals a biological sensitivity to persimmon, with specific immunoglobulin E levels at 0,79 kU/L, as well as a positive skin prick tests to persimmon fresh extract. An oral provocation test was also conducted, demonstrating no reaction to the ingestion of 1 then 2 grams of persimmon, but a similar reaction to the initial episode when ingesting 5 grams (resulting in a total cumulative dose of 8 grams). Our observation describes the pediatric manifestations of this allergy along with a literature review.

Long Term Remission of Capillary Leak Syndrome Associated with Monoclonal Gammopathy with Progression to Multiple Myeloma After Autologous Stem Cell Transplantation: a Case Report and Review of the Literature.

Clarkson's disease is a very rare entity characterised by acute episodes of systemic oedema and severe hypotension associated with paraproteinaemia. Its classical treatment relies on methylxanthine combined with terbutaline. Although this prophylactic therapy reduces the mortality rate, relapses are frequent. Eighty percent of patients with Clarkson's disease present with monoclonal gammopathy of unknown significance (MGUS). The risk of progression to multiple myeloma is 1% per year. Here, we present a 49-year-old woman who suffered multiple such episodes requiring treatment in the intensive care unit. Treatment with terbutaline and theophylline was ineffective. She was diagnosed with multiple myeloma (MM) 8 years after the first of these acute episodes. Antimyeloma treatment with bortezomib and dexamethasone was started, followed by autologous haemopoietic transplantation, with no further acute episodes since then. Our case is, to our knowledge, unique because eradication of MM was followed by complete disappearance of acute episodes of capillary leakage. Our case report is also the first to support the use of bortezomib and dexamethasone in this setting. Furthermore, autologous peripheral blood progenitor cell transplantation consolidated the MM stringent complete remission achieving a very long progression-free survival (> 11 years) of both MM and Clarkson's disease.

Hereditary C1-inhibitor deficiency angioedema (C1-INH-HAE) in children – practical considerations

Hereditary angioedema is a rare, autosomal dominant, potentially life-threatening disorder usually resulting from C1-esterase deficiency or dysfunction. Clinical manifestations include unpredictable, acute, recurrent episodes of well-demarcated oedema occurring without pruritus, most commonly affecting the face, trunk, extremities, but also, due to mucosal involvement, the respiratory and gastrointestinal systems. Although oedema resolves spontaneously within 2–5 days, the skin lesions are disfiguring, painful and disrupt daily functioning, while abdominal attacks are very painful and often lead to hospital admissions and unnecessary surgery. In addition, laryngeal oedema, which affects at least half of patients, is life-threatening and, in many cases, leads to fatal asphyxia. Therefore, early diagnosis and implementation of proper therapeutic management as soon as possible are crucial. In recent years, significant advances have been made in the treatment of hereditary angioedema. Initially, only intravenous drugs administered during attacks were available in medical facilities. Patient education has allowed for home therapy. The next step was the introduction of subcutaneous injections, which were more convenient for patients. Finally, long-term prophylactic treatment, which completely relieves symptoms and allows for a normal life, has gained importance. Unfortunately, the high cost of these therapies remains a problem. This paper reviews in detail the clinical picture and differential diagnosis of the disorder, as well as modern treatment approaches, with special focus on the distinctive features in children.

A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson disease.

Vascular dysfunction resulting from endothelial hyperpermeability is a common and important feature of critical illness due to sepsis, trauma, and other conditions associated with acute systemic inflammation. Clarkson disease [monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS)] is a rare, orphan disorder marked by spontaneous and recurrent episodes of hypotensive shock and peripheral edema due to widespread vascular leakage in peripheral tissues. Mortality from acute flares approaches 30% due to lack of effective therapies. We evaluated a monoclonal antibody (4E2) specific for the endothelial receptor tyrosine kinase Tie2 in ISCLS models. 4E2 activated Tie2 in ISCLS patient-derived endothelial cells and reduced baseline and proinflammatory mediator-induced barrier dysfunction. 4E2 also reduced mortality and/or vascular leakage associated with systemic histamine challenge or influenza infection in the SJL/J mouse model of ISCLS. These findings support a critical role for Tie2 dysregulation in ISCLS and highlight a viable therapeutic approach to this catastrophic disorder.

Phase II Study of Danazol with Plasma Exchange and Corticosteroids for the Treatment of Thrombotic Thrombocytopenic Purpura

Background: Ahn and colleagues reported a decrease in plasma exchange (PE)/plasma infusion requirement with danazol in seven cases of thrombotic thrombocytopenic purpura (TTP) (Ahn Blood 2006;108(11):1057a). We reported an increase in platelet count (PLT) within 24 hours with danazol in two of three cases of human immunodeficiency virus-associated TTP resistant to PE (Torri Transfusion 2010;50:86a). In 2009, we initiated a phase II study of danazol with PE and corticosteroids (CS) for the treatment of TTP. This trial was approved by the institutional review board and was registered at ClinicalTrials.gov (ID# NCT00953771). We report the final results. Aims: To determine if danazol reduces number of PE's, time to remission (TR), and length of stay (LOS) when administered with standard therapy for the initial treatment of TTP. Methods: Experimental Group (EG): Patients with TTP (PLT < 100,000/µL and microangiopathy) receive daily PE, prednisone 1 mg/kg, and danazol 600 mg. Following remission (PLT > 150,000/µL for three consecutive days), PE is tapered to every other day for one week then stopped. Then prednisone is tapered weekly over four weeks then stopped. After one week danazol is tapered by 200 mg weekly then stopped. Historical controls (HC): Patients treated for TTP at St. Luke's-Roosevelt Hospital Center with PE with or without CS from 2000 to 2007 (n=20). Relapse definition: PLT < 100,000/µL with microangiopathy > 30 days after remission. Total number of PE's, TR, LOS, and continuous response rates are compared between the 2 groups. Accrual target: 16 patients to detect a 40% decrease in the number of PE's with 80% power and a level of significance of 0.05.The study was terminated in 2018 due to low accrual. Results: Nine patients were enrolled. Mean number of PE's (days) was 14.8 (EG) and 16.1 (HC), mean TR (days) was 11.4 (EG) and 11 (HC), and mean LOS (days) was 27.3 (EG) and 24.9 (HC), p > 0.05. Four patients in HC had a total of 6 relapses at our institution at a median of 28.25 months, range 2.75 to 97 months after the initial event. One patient in EG relapsed 43 months after study enrollment. One patient in EG died from an unrelated cause. None of the additional seven patients in EG have relapsed during a median follow-up of 49 months, range 12 to 125 months. One episode of pulmonary edema and one episode of hypotension occurred in EG, for which treatment was not discontinued. Discussion: Our study shows that danazol does not reduce PE requirement, TR, or LOS during treatment of TTP, but may prevent relapse. This pattern of response is similar to that which has been observed with rituximab. In a phase 2 study of rituximab in conjunction with PE and CS for the treatment of TTP (Scully Blood 2011), in which results were compared with historical controls who did not receive rituximab, median number of PE's (days) and median LOS (days) were 16.5 and 16.5 in the rituximab group versus 18.0 and 20 in the historical control group, p=ns. Ten percent of patients relapsed at a median of 27 months in the rituximab group whereas 57% of patients relapsed at a median of 18 months in the historical control group. Of interest, the cost of rituximab 375 mg/m 2 weekly for 4 weeks as given would have been approximately $ 25,366.50. The cost of danazol in our protocol would have been approximately $ 2196.00. Caplacizumab is a humanized monoclonal antibody fragment that inhibits von Willebrand factor binding to platelet glycoprotein lb-IX-V. In a phase 3 study (Scully N Engl J Med 2019), caplacizumab in conjunction with PE and CS for the treatment of TTP led to reduced PE's, time to normalization of platelet counts, and LOS, but increased relapses in comparison with placebo. In 2020, the International Society on Thrombosis and Haemostasis strongly recommended adding CS to PE for the treatment of TTP and conditionally recommended adding rituximab and caplacizumab to PE and CS (Zheng J Thromb Haemost 2020). Conclusion: Danazol in conjunction with PE and CS may be a low-cost option to prevent relapses of TTP.

THU357 A Case Of Recurrent Insulin-induced Edema In A Pediatric Adolescent Patient

Abstract Disclosure: G.J. Mora Calderon: None. R.L. Aguirre: None. D. Preston: None. Introduction: Insulin induced edema is a very rare complication seen after initiation of insulin therapy or after escalation of previous insulin regimen in patients with diabetes. The exact incidence of this condition is unknown. Insulin induced edema seems to have a female predominance and is associated primarily with patients who are underweight. The severity of insulin induced edema can range from mild localized peripheral edema to more severe and generalized complications, including cardiac failure and serosal effusions. There is a higher risk for severe complications in older patients with pre-existing cardiac, hepatic, or renal conditions. Usually, the course is benign and self-resolved without any intervention. Severe and prolonged cases have been reported to need adjuvant therapy (e.g diuretics or sympathomimetic agents) or sodium-restricted dietary regimens. Increasing blood glucose target with a decreased insulin regimen has been proposed as a possible option to prevent insulin induced edema. We present a 14 year-old-male patient with history of poor controlled type 1 diabetes mellitus and recurrent insulin-induced edema after strengthening of his insulin therapy. Case Presentation: A 14-year-old male with poorly controlled type 1 diabetes mellitus presented to the emergency with pitting edema of his face and hands that started a week after intensification of his insulin regimen. His weight increased from 73 kg to 84 kg in about 10 days. His vital signs at presentation were stable and besides the pitting edema, the rest of the physical examination was unremarkable. His mother reported a previous episode of edema that occurred approximately a year before this presentation and about a month after he was first diagnosed with diabetes mellitus. His most recent HbA1c was 14.4%. Patient was admitted for evaluation. Electrocardiogram, transthoracic echocardiogram, chest x-ray, and multiple laboratories (including a comprehensive metabolic panel, complete blood count, B-type natriuretic peptide, urine microalbumin, and thyroid function test ) came back all normal. The edema slowly improved and was eventually discharged. No adjuvant therapy was needed during his hospitalization. Conclusion: The diagnosis of insulin induced edema is primarily based on the exclusion of other etiologies. Most cases reported only one episode after initiation of insulin therapy or after escalation of previous insulin regimen, but it can happen multiple times as noted in our patient. Presentation: Thursday, June 15, 2023

An Unusual Cause of Tricuspid Regurgitation and Right Heart Failure

Abstract A 64-year-old female presented with complaints of multiple episodes of palpitations, pedal edema, and abnormal neck pulsations for the past 6 months. Pulse was regular and jugular venous pulse elevated with a prominent V wave and sharp Y descent. Cardiovascular examination revealed grade II left parasternal heave, epigastric pulsations, right ventricle S3, and a grade III high-pitched blowing pansystolic murmur at the left lower sternal border. Electrocardiogram, chest X-ray, and 24-h Holter monitoring were normal. We clinically diagnosed isolated right heart failure with nonhypertensive tricuspid regurgitation. Transthoracic echocardiography showed a huge right atrial tumor prolapsing into the right ventricle and right ventricular outflow tract along with significant tricuspid regurgitation. The tumor was removed surgically. Histopathological examination confirmed the diagnosis of right atrial myxoma. Right atrial myxoma presenting as pure tricuspid regurgitation and right heart failure is rarely reported in the literature.

#4949 COMBINED ORAL DIURETICS: A BETTER ALTERNATIVE FOR NEPHROTIC EDEMA THAN INTRAVENOUS FUROSEMIDE?

Abstract Background and Aims Edema is a serious complication of nephrotic syndrome and is the main reason why patients usually address to a doctor. There is no guideline on managing nephrotic edema. Besides non pharmacological interventions such as sodium and water restrictions, most doctors would choose high doses of intravenous furosemide as the first option, but still many patients fail to properly decrease their volume overload, as they become diuretic resistant. Amiloride, an ENaC mediated diuretic, is an optimistic management option, especially when used with other diuretics. The aim of the present study was to assess the non inferiority of the combined oral diuretics furosemide and the fixed combination of hydrochlorothiazide/amiloride diuretics with intravenous furosemide in diuretic resistant nephrotic edema. Method We conducted a prospective randomized trial in 22 patients with diuretic resistant nephrotic edema. Based on a computer-generated randomization we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day). Clinical and laboratory measurements were performed daily, for five days (body weight, urinary output, blood pressure and hydration status by bioimpedance twice, creatinine, urea, albumin, hematocrit, Na, K, Ca, Mg, bicarbonate, pH). The primary outcome was weight and hydration status change from baseline to day 5. Secondary outcomes were safety outcomes (low blood pressure, severe dyselectrolytemia, acute kidney injury or aggravated hypervolemia). Results The patients were equally distributed between the two groups. Mean age was 47,77±15,97 (54,5% females and 45,5% males). Half of the patients had membranous nephropathy (45,5%), followed by minimal change disease (22,7%) and lupus nephritis (9,1%). 86,4% of patients had their first episode of nephrotic edema. The mean weight decrease was of significantly larger magnitude in the combined oral diuretics group compared with the intravenous furosemide group (-7,97±2,83 [SD] vs -4,5±2,6 [SD] kg; p = 0,018). Although the increase in 24-hour urine sodium excretion was higher in combined oral diuretics as compared to intravenous furosemide group, this increment was not statistically significant different (26,79±33,48 [SD] vs 16,04±42,81 mmol/24 h [SD]; p = 0,5). Mean values for changes in systolic and diastolic BP, 24-hour urine volume, hydration status measured by bioimpedance were not significantly different between the two groups. A total of 5 patients could not be followed through, 4 in the intravenous furosemide (two patients experienced low blood, one patient had no response to iv furosemide and one patient suffered from insomnia due to iv pump) and one patient in the oral combination of diuretics group had severe hyperkalemia (>6,5 mmol/l). Conclusion Combined oral diuretics with furosemide, amiloride and hydrochlorothiazide is more effective and safer than intravenous furosemide for the treatment of refractory nephrotic edema. These results make amiloride a promising diuretic and further trials with larger sample sizes and longer follow-up are needed in this regard.

Are pediatricians familiar with hereditary angioedema?

BackgroundHereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. MethodsAn online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. ResultsFour hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p < 0.001). ConclusionKnowledge about HAE among Brazilian pediatricians, whether board certified in Allergy and Immunology or not, was unsatisfactory. HAE is a rare disease, largely unknown among physicians; therefore, increasing awareness may lead to improvement in diagnosis and treatment.

P39 MANAGEMENT OF A CASE OF LAST REMAINING PATENT VESSEL

Abstract A 72–year–old hypertensive, dyslipidemic and smoker (20 cig/day) gentleman was admitted to the emergency department for pulmonary edema. Past medical history included COPD, anterior MI treated with PCI and stenting of proximal LAD 5 years back, recent TIA. He was admitted to cardiac intensive care unit and treated with CPAP, IV furosemide and norepinephrine. Echocardiogram showed severe ventricular dysfunction (LVEF 20%) and severe functional mitral regurgitation; lab tests pointed out mild troponin elevation (50 ng/L) and high levels of BNP (1300 pg/mL). After stabilization, he underwent coronary angiography: in–stent CTO of LAD, critical stenosis of distal LM and ostio–proximal LCX (last remaining patent vessel, LRPV); hypoplastic RCA. At the end of angiography, new episode of pulmonary edema that required treatment with inotropes, CPAP and diuretics. Considering hemodynamic instability and high surgical risk (combined STS 37%), the Heart Team decided to proceed to PCI with mechanical circulatory support with Impella CP. From left radial access we achieved advancement of JR4 guiding catheter with guide extension in right common iliac artery. We performed angiography and then put a coronary guidewire in superficial femoral artery to facilitate right femoral access (angio–guided). From this femoral access we implanted Impella CP device. From left radial access we performed PCI: cannulation with JL 3 guiding catheter, wiring with Sion Blue ES guidewire, pre–dilatation with NC balloons until 3.0 mm diameter, stenting of LM–LCX with 1 DES 4.0/32 mm, post–dilatation with NC balloons (4.5 and 5.0 mm diameter). Good angiographic result; IVUS examination revealed good expansion and apposition of stent. Femoral access was closed with 2 Perclose Proglide. Patient was then monitored in cardiac intensive care unit, with clinical improvement and without complications. 10 days after PCI the patient, asymptomatic, was discharged. The echocardiogram displayed betterment of contractile function (LVEF 28%) and of mitral regurgitation (now moderate). At 4–month follow–up visit, patient is paucisymptomatic (NYHA class II), without angina episodes, with good quality of life in guideline–directed optimal medical therapy. Critical disease of LRPV is a severe condition, with unpredictable evolution and poor prognosis. PCI of LRPV in HFrEF patients is an high–risk PCI scenario in which mechanical circulatory support with Impella can prove to be essential.

Eosinophilia and potential antibody cross-reactivity between parasites in a child with pinworm and immune dysregulation: a case report

BackgroundIntestinal parasitic infections are common in humans, especially among young children. These conditions are often asymptomatic and self-limiting, and diagnosis is mainly based on the search for ova and parasites in the stools since serology may be biased due to cross reactivity between parasites. Pinworm is common in children and is not usually associated with hypereosinophilia; adhesive-tape test is the gold standard testing for the microscopic detection of Enterobious vermicularis (Ev) eggs.Case presentationA 13-year-old boy was referred due to a self-resolving episode of vomiting and palpebral oedema after dinner, together with a history of chronic rhinitis, chronic cough, absolute IgA deficiency and Hashimoto’s thyroiditis and hypereosinophilia (higher value = 3140/µl). On evaluation we detected only palpable thyroid and hypertrophic nasal turbinates. Food allergy was excluded, but skin prick tests showed sensitization to house dust mites and cat epithelium and spirometry showed a marked obstructive pattern with positive bronchodilation test prompting the diagnosis of asthma for which maintenance inhaled treatment was started. Chest x-ray and abdomen ultrasound were negative. Further blood testing showed positive IgG anti-Echinococcus spp. and Strongyloides stercoralis and positive IgE for Ascaris, while Ev were detected both by the adhesive tape test and stool examination, so that we made a final diagnosis of pinworm infection. Three months after adequate treatment with pyrantel pamoate the adhesive-tape test turned out negative and blood testing showed a normal eosinophil count. The child later developed also type 1 diabetes.ConclusionsWe suggest the need to investigate for enterobiasis in children with hypereosinophilia and to consider autoimmunity as a potential confounding factor when interpreting serology for helminths.

АНАЛИЗ ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ПРИМЕНЕНИЯ ПАТОГЕНЕТИЧЕСКОЙ ТЕРАПИИ С ЦЕЛЬЮ КУПИРОВАНИЯ АТАК У ДЕТЕЙ С НАСЛЕДСТВЕННЫМ АНГИОНЕВРОТИЧЕСКИМ ОТЕКОМ

Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare (orphan) autosomal-dominant disease related to primary immunodeficiencies with a defect in the complement system and is characterized by recurrent, unpredictable edema attacks involving various organs and tissues. The recurrent episodes of edema are not amenable to the usual therapy methods and often are life-threatening conditions, especially in pediatric patients. The most pressing issue for the attending physician is the choice of the drug from the available range, taking into consideration its mechanism of action, route of administration and other parameters. This Article summarizes the properties of drugs currently available for the HAE attacks relief in pediatric patients in Russia, including the results of clinical trials, and the Authors’ own experience in the use of Icatibant and a human C1-esterase inhibitor as drugs of choice for the edema relief in the pediatric patient cohort. The purpose of this retrospective study was to evaluate the equivalence and safety of Icatibant and a C1-inhibitor concentrate for the edema management. Materials and methods used: the study included 34 HAE-C1-INH patients who had experienced 302 attack episodes in total. The inclusion criteria were a registered episode of angioedema in a patient aged 0 up to 18 y/o, confirmed HAE diagnosis and one of the two studying drugs intake within 24 hours after the onset of the first edema symptoms. Patients were administered with Icatibant, subcutaneously, or with C1-esterase inhibitor, intravenously. The efficacy was evaluated by comparing the presence of relief and/or relief of symptoms during the mentioned therapy. All of the adverse reactions during the therapy were also recorded in order to assess the drugs’ safety. Results: a total of 302 attack episodes were analyzed in 34 patients in the period from 2016 to 2021. Icatibant was used in 225 (74.5%) cases in 34 patients, and human C1-esterase inhibitor was used in 77 (25.5%) cases in 27 patients. It was allowed to use both drugs in the same patient in different angioedema episodes. The age of the children included in the analysis at the time of the first episode ranged from 1 to 14 y/o (Me 4.5 y/o). The edema was peripheral in most of the studied cases. The drugs were found to be equivalent in terms of duration until the edema symptoms’ relief (Me duration was 30 min. in both drugs, p=0.005), but not in terms of duration until the symptoms cut-off, - with greater values for Icatibant compared to the C1-inhibitor human esterase (p=0.394). Conclusion: a relatively similar efficacy and safety of both drugs as well as the possibility for their use in all age groups were recorded. It is therefore necessary to take into consideration the availability of the satisfactory venous access when choosing a drug for stopping the edema; the patient’s age (in order to ensure the fastest possible administration of the drug counting from the onset of edema); the remoteness of a patient’s location during the attack from the nearest available and satisfying medical facility; the patient’s and/or his/her parent(s)/caretaker(s) preferences. The study demonstrated that both Icatibant and the C1-inhibitor concentrate have high safety profile.

Prevention of Recurrent Attacks of Hereditary Angioedema (HAE): Berotralstat and Its Oral Bioavailability.

Hereditary angioedema (HAE) is a condition characterized by episodes of cutaneous and submucosal edema. Angioedema of the extremities and abdominal attacks are the most common manifestations of the disease. It can also affect the upper airways with the potential of becoming life-threatening. The two most common causes of HAE are a deficiency of C1 inhibitor (classified as type 1 HAE) or a dysfunction of C1 inhibitor (type 2 HAE). A malfunction or deficiency of C1 inhibitor leads to an overactivated plasma kallikrein (an inflammatory vasoactive peptide), that increases bradykinin, mediating the angioedema episodes in patients with HAE. To minimize the difficulties of this pathology and to improve patients' quality of life, prevention of this condition is essential. Berotralstat is a unique option for oral administration for routine prophylaxis. This drug acts by binding to kallikrein and reducing its plasma activity, lowering bradykinin levels. Open-label studies have demonstrated the effectiveness of a single daily dose of berotralstat 150 mg in preventing HAE attacks. This review aims to examine studies performed to elucidate the efficacy, safety, and tolerability of berotralstat.

Burden of illness seen in hereditary angioedema in Japanese patients: Results from a patient reported outcome survey.

Hereditary angioedema (HAE) is a potentially life-threatening rare disease, which is mainly caused by the deficiency or dysfunction of C1-esterase inhibitor, and characterized by spontaneous, recurrent episodes of edema in various parts of the body including internal organs and the laryngeal area. Delayed diagnosis and treatment increase the burdens and risks of this condition. The current study aimed to understand the burden of illness for HAE patients in Japan before and after diagnosis through a patient reported outcome survey. A survey instrument was distributed to 121 adult patients with HAE by a patient organization via HAE treating physicians between July and November in 2016. Seventy patients (57.9%) returned the questionnaire. Patients reported high levels of medical resource utilization, including emergency procedures and services. Episodes of receiving laparotomy were somewhat less after diagnosis with HAE than before, but no apparent difference in episodes of tracheotomy between before and after the diagnosis. The economic burden, including direct and indirect medical costs, was highest before diagnosis, but still perceived as substantial after diagnosis. Patients reported disruption of work and school life, with 40% reporting that they miss 10 or more days from work or education per year. Sixty percent of patients reported that HAE affected their daily activities. We concluded that HAE is associated with considerable physical, social, economic and psycho-social burdens even after diagnosis, and that higher attack frequency is associated with a heavy disease burden for patients in Japan.