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Background: To assess the safety, tolerability, and pharmacokinetic (PK) profile in humans of the novel inhaled epithelial sodium channel blocker ETD001. Method(s): Inhaled ETD001 or placebo, delivered via nebulizer, have been administered in a 3:1 ratio to 96 healthy subjects in a blinded, first-inhuman clinical trial (ClinicalTrials.gov Identifier: NCT04926701). The study consisted of two parts. Part A evaluated single ascending doses (SADs) up to 10.8 mg, and Part B evaluated multiple ascending doses (MADs) up to 3.1 mg once daily (QD) for 7 days and 4.65 mg twice daily (BID) for 14 days. Safety was assessed by monitoring for adverse events (AEs), laboratory safety tests (including blood potassium monitoring), vital signs, 12-lead electrocardiogram (ECG), and spirometry. Systemic exposurewas assessed using serial pharmacokinetic blood draws. Result(s): Therewere no serious AEs. Twenty-four subjects reported 38 AEs, all of mild to moderate intensity and all resolved. There were no clinically relevant changes in laboratory safety tests, vital signs, ECGs, or spirometry measurements. All blood potassium assessments were within normal range at all doses. Three subjects withdrew in Part B;all withdrawals were considered unrelated to study drug: one on day 6 from the 3.1-mg QD cohort for personal reasons, one after the first dose of the 3.1-mg BID cohort because of vasovagal syncope at time of venipuncture triggering atrial fibrillation that spontaneously resolved, and one on Day 4 of the 3.1- mg BID cohort because of a positive COVID-19 test. Pharmacokinetic parameters were approximately dose proportional in Part A, with peak concentrations 1 to 2 hours after dose and exposure out to 12 to 24 hours at all doses, indicating good lung retention. Part B plasma concentrations displayed dose-independent kinetics and showed minimal accumulation, with a mean of 1.11-fold observed over 14 days. Conclusion(s): ETD001 was well tolerated at single doses up to 10.8 mg and multiple doses of 3.1 mg QD for 7 days and 4.65 mg BID for 14 days. The wide safety margin is predicted to enable doses capable of durable target engagement in the lung, which are expected to enhance mucociliary clearance in people with cystic fibrosis.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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COVID-19 is an emerging pandemic. The course and management of the disease in the liver transplant setting may be difficult due to a long-standing immunosuppressive state. In Egypt, the only available option is living donor liver transplantation (LDLT). In our centre, we have transplanted 440 livers since 2008. In this study, we report a single-centre experience with COVID-19 infection in long-term liver transplant recipients. A total of 25 recipients (5.7 %) had COVID-19 infections since March 2020. Among these recipients, two developed COVID-19 infections twice, approximately three and two months apart, respectively.Copyright © 2021 The Author(s)
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A 23-year-old male patient received moxifloxacin, recombinant human interferon alpha-2b for injection, and lopinavir and ritonavir for 7 days for novel coronavirus pneumonia. There was no abnor-malityof serum potassium. Moxifloxacin was stopped, Qingfei Paidu decoction() was given, and then the patient's serum potassium began to rise. On day 10 after taking the decoction, laboratory tests showed serum potassium 5.7 mmol/L and the patient was diagnosed with hyperkalemia. Insulin injection 4 U diluted to 5% glucose injection 250 ml was given once by IV infusion, and then the serum potassium decreased to 5.0 mmol/L 6 hours later and 4.6 mmol/L 2 days later. After 5 days, the serum potassium rose again and finally to 5.4 mmol/L on day 17 after taking the decoction. Insulin was given once that day and 2 days later once daily according to the previous method. Then the serum potassium decreased and did not rise again. The patient recovered from novel coronavirus pneumonia and was discharged on day 28 after hospitalization.Copyright © 2020 by the Chinese Medical Association.
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Introduction: Acute kidney injury (AKI) occurs in 0.5 to 25% of hospitalized COVID-19 patients. Clinical severity and renal involvement are due to inflammation, immune and endothelial dysfunction. On the other hand, risk factors such as age, comorbidities, mechanical ventilation requirement, hypovolemia and MAP <65 mm Hg are associated with AKI development. This study aim to evaluate the development of AKI and determine the relationship between serum creatinine and inflammatory. Method(s): A single center, retrospective study involving 166 patients under the diagnosis of moderate to severe COVID-19 infection in Hospital General Regional 110 Oblatos, Guadalajara, Mexico. A consecutive sample was approached. AKI was determined and classify when changes in serum creatinine met KDIGO definition. Demographics, clinical and biochemical data, risk factors for AKI and RRT prescription were assessed and reported during diagnosis and discharge. Outcome measures were renal recovery, mortality and causes of death. Differences were compared using 2-sample t test for continuous variables and chi-square for categorical variables. Relationship between creatinine changes and inflammation markers were assessed using Pearson correlation coefficients. All statistical tests were performed using SPSS 28.0 and a P < 0.05 level of significance. Result(s): Mean age 59 +/- 18.38 years. 60 cases (36%) were diagnose as AKI. 41% were in stage 1, whereas 35% and 24% made up stage 2 and 3, respectively. Changes in serum creatinine (SCr) correlated with gender (r=0.155, p 0.48), changes in hemoglobin (r= -0.384, p < 0.01), neutrophil/ lymphocyte ratio (NLR) (r= 0.229;p 0.003), serum phosphate (r= 0.555, p < 0.01), serum calcium (r= -0.210, p < 0.011), serum potassium (r= 0.555, p < 0.01), serum magnesium (r= 0.212, p < 0.012), D-dimer (r= 0.246, p 0.02) and (r= -0.322, p < 0.01). After adjusting model for cofounders, hospitalization length and age (OR: 3.03, CI 0.39, 11.56, p=0.033) trend to be a significant data, other cofounders in relation to the presence of AKI o changes in SCr were no significant with other potential outcomes. [Formula presented] Conclusion(s): The present study highlighted that the presence of AKI is associated the increased of inflammation, but the current evidence limits the outcomes in already none predictive factors. Further studies are needed to establish early strategies aimed to prevent AKI and its evolution in COVID-19 patients and pandemics ahead. No conflict of interestCopyright © 2023
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Introduction: The pandemic coronavirus disease 2019 (COVID-19) substantially impacts the public health care, especially in Thailand. Acute kidney injury (AKI) is one of the common complications in patients afflicted with COVID-19 infection. This study purposes to study the incidence, risk factors, and association between AKI and mortality among hospitalized primary COVID-19-infected patients. Method(s): This is a retrospective, observational study. Data of 502 adult patients with confirmed COVID-19 infection and admitted in Lerdsin Hospital from August 1, 2021, to April 30, 2022, were analyzed. AKI was diagnosed based on the extended Kidney Disease Improving Global Outcomes (KDIGO) criteria. Clinical characteristics and laboratory data were compared between two groups of patients: with and without AKI. Independent risk factors of AKI and the association between AKI and mortality were reported using adjusted odd ratios (aORs). Result(s): Two hundred and thirty-four patients (46.6%) were male. The mean age was 60.49+/-18.46 years old. AKI was diagnosed in 135 (26.9%) patients, and proportion of these patients decreased as the stage advanced: stage 1 (66.6%), 2 (17.1%), and 3 (16.3%). The most common comorbidities were hypertension (50.2%), diabetes mellitus (33.9%), and dyslipidemia (27.3%). Three hundred and eighty patients (75.7%) had pneumonia. The diagnosis of COVID-19 pneumonia and lower oxygen saturation were reported more in patients with AKI (p <0.001). Patients with AKI were more likely to have comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), hypertension (HT), coronary artery disease (CAD), and cerebrovascular disease (CVD). Further, lower rates of steroid administration and COVID vaccination were observed in this group. The incidence of overall in-hospital mortality was 21.3%, composed of 11.3% of patients with AKI and 10% of patients without AKI. AKI was associated with higher mortality with aORs of 2.16 (95% confidence interval [95% CI], 1.22-3.83). Independent risk factors of incident AKI were: male gender (aORs, 2.35;95% CI, 1.43-3.88), age >= 60 years (aORs, 2.54;95% CI, 1.46-4.23), CKD (aORs, 5.3;95% CI, 1.67-16.8), CAD (aORs, 3.81;95% CI, 1.23-11.79), DM (aORs, 1.75;95% CI, 1.04-2.94), and serum bicarbonate <20 mEq/L (aORs, 2.77;95% CI, 1.64-4.69). Patients with a history of COVID-19 vaccination and low serum potassium (<4 mEq/L) were less likely to have AKI (aORs, 0.49, 95% CI, 0.26-0.91 and aORs, 0.38, 95% CI, 0.23-.064, respectively). Conclusion(s): Independent risk factors, including gender, age, comorbidities, and laboratory results, had predictive values for AKI. COVID-19 vaccination remains one of the crucial strategies to prevent AKI in hospitalized patients. No conflict of interestCopyright © 2023
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Introduction: Acute kidney injury (AKI) in COVID-19 infection is common, especially in severe diseases, and is associated with worsening outcomes. Data from many countries demonstrate differences in the incidence and risk factors of AKI. However, there is limited data available for AKI among severe COVID-19 patients in Thailand. This study aims to investigate the incidence and identify AKI risk factors in patients with severe COVID-19 infection at tertiary care hospitals. Method(s): In this retrospective cohort study, we analyzed data of patients admitted to the intensive care unit with PCR-confirmed diagnoses of COVID-19 infection from electronic medical records at Thammasat University Hospital. All patients who were admitted between 1st January 2021 and 30th June 2022 were included. Result(s): Of the 215 severe COVID-19-infected patients included, 134 (62.33%) experienced AKI injury. 81 (60.45%), 19 (14.18%), and 34 (25.37%) patients had AKI KDIGO stage 1, 2, and 3, respectively. From the univariate logistic regression analysis, the risk factors of AKI in COVID-19 patients were female, older age, preexisting hypertension, dyslipidemia, coronary artery disease, chronic kidney disease (CKD), higher APACHE II score, low serum albumin, high serum potassium, low serum bicarbonate, presence of proteinuria from dipstick and used of vasoactive drugs. Multivariate analysis showed that pre-existing CKD [odds ratio (OR) 13.95, 95%CI 2.24-86.88;p = 0.005], presence of proteinuria (OR 7.33, 95%CI 1.5-35.78;p=0.014) and APACHE-II score (OR 1.78, 95%CI 1.02-1.36;p=0.024) were independently associated with developing AKI. Multivariate analysis showed that AKI was associated with 30-day mortality with an OR of 4.34;95%CI 1.63-11.51 (p=0.003). Among AKI-patient survivors, 27 patients (20.15%) fully recovered their renal function, 22 patients (16.42%) were not recovering, and 11 patients (8.21%) required kidney replacement therapy during admission. The most common dialysis indication was volume overload. Conclusion(s): AKI in severe COVID-19 patients was common. Pre-existing CKD, presence of proteinuria, and higher APACHE II score were independently associated with AKI. Only one-fifth of AKI survivors had full renal recovery. Thus, the COVID-19 patients with these risk factors should be closely monitored and treated cautiously in order to prevent AKI development. No conflict of interestCopyright © 2023
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Toxic epidermal necrolysis (TEN), is an acute, life-threatening emergent disease involving the skin and mucous membranes with serious systemic complications. It is characterized by widespread epidermal sloughing. Drugs are the most common triggers of TEN, but infection, vaccination, radiation therapy and malignant neoplasms can all induce it in susceptible patients. We report two cases in whom a hair dye and a COVID-19 vaccine (BioNTech, Pfizer) were believed to be the causative agents. These patients have to undergo repeated debridements of the necrotic tissue. In this manuscript the anesthetic management of TEN patients is discussed. Detailed preoperative evaluation, aggressive fluid and electrolyte replacement, avoidance of hypothermia during debridement, minimizing anesthetic agents and limiting traumatic procedures are key points in the management.Copyright © 2023 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.
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Aim: We primarily aimed in this study was to evaluate risk factors for COVID-19 infection and if any association between dialysis inadequacy in COVID-19 infection in maintenance hemodialysis (MHD) patients. Secondly aimed to describe prevalence and risk factors associated with long-lasting symptoms of non-deceased COVID-19 MHD patients before vaccination. Material(s) and Method(s): One hundred one MHD patients infected with COVID-19 and 100 MHD patients without the infection were enrolled in this retrospective cross-sectional study. Risk factors for mortality, need to intensive care unit (ICU) stay and long-lasting symptoms were analyzed. Result(s): The mean age of patients was 59.13+/-13.58 years. COVID-19 infected patients had significantly higher number of patients with DM, COPD, CHF. The need for ICU was found to be statistically significantly higher in patients with COPD and DM. In our results, the patients who had lower Kt/V at admission hospital had more than 5 fold higher rate of COVID-19 those have higher Kt/V. We analyzed risk factors for mortality at, one year included higher age, higher CRP and lower base-line Kt/V were diagnostic criteria. Older MHD patients had a high frequent of long-lasting symptoms. Low Kt/V, low hemoglobin level and high CRP level associated with a higher risk of long-lasting symptoms (p=0.00, p=0.001, p=0.02) Discussion: We conclude that DM, CHF, COPD, older age, obesity were poor prognostic factors for in infected with COVID-19. Dialysis adequacy parameters of Kt/V, serum albumin level, hemoglobin level were significantly lower in need to ICU and deceased patients.Copyright © 2023, Derman Medical Publishing. All rights reserved.
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Aim: The assessment of serum electrolytes at the time of initial presentation of the patient with respiratory tract infection possibly causing lung parenchyma and pulmonary vasculature damage and serial monitoring during the stay could be beneficial in order to determine when and how to take remedial action when necessary. Methodology: A non-probability sampling was done on 139 subjects with suspected respiratory tract infection. For confirmation, culture, MTB PCR, COVID-19 testing was done to diagnose the nature of infection. Serum electrolytes were tested on chemical analyses Alinity instrument. Results: Most common infections found were COVID-19 and bacterial (n=59) collectively in a co-morbid state. Mycobacterium tuberculosis and fungal infections were also found in (n=8) each. Electrolytes imbalance was markedly observed in high prevalence amongst Tuberculosis and COVID-19 patients but also showed significant association with other respiratory investigated infections. Conclusion: A robust association of electrolyte imbalance was found in all cases presented with upper or lower respiratory tract infections.
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Background: COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, particularly known for its respiratory symptoms. Nevertheless, a wide variety of clinical manifestations has been associated with COVID-19, including Kawasaki disease, Guillain- Barré syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical Case: A 55-years-old woman, affected by immune thrombocytopenia on prednisone therapy, presented with intense fatigue, hyporexia and vomit. She had no fever, no cough, nor other symptoms. She referred a quick prednisone decalage in previous days. ABG showed metabolic alkalosis, severe hyponatremia and hypokalemia. The patient tested positive for SARS-CoV-2. Further investigation showed euvolemic hyponatremia (102 mEq/L) with normal urine osmolality (275 mOsm/Kg), findings consistent with COVID-19-related SIADH. We set a corticosteroid therapy with Prednisone 37,5 mg/die for 5 days, then 25 mg/die for 2 days. After 7 days of hospitalization, the patient tested negative for SARS-CoV-2. In the meantime, kalemia and natremia were back in range. Conclusions: Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in COVID-19 patients.
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INTRODUCTION: Sodium polystyrene sulfonate (SPS) has been the mainstay of therapy for the treatment of hyperkalemia, but it has been associated with case reports of gastrointestinal injuries. In May 2018, the Food and Drug Administration approved sodium zirconium cyclosilicate (SZC) for the treatment of hyperkalemia, which demonstrated efficacy in achieving restoration of normokalemia after 24 to 72 hours. In January 2020, SZC replaced SPS as the preferred potassium binder at our institution based on published literature. The objective of this study was to evaluate the resolution of hyperkalemia with SZC containing regimens compared to SPS containing regimens within 24 hours. METHODS: This retrospective chart review was approved by the Institutional Review Board. Patients who were 18 years of age and older and received at least one dose of SZC (from January 2020 to November 2020) or SPS (from January 2019 to September 2019) for the treatment of hyperkalemia were reviewed to be included in the study. Patients who were critically ill, COVID-19 positive, on chronic hemodialysis, on chronic potassium binders, or treated based on a hemolyzed potassium level were excluded from the study. The primary endpoint was the restoration of normokalemia within 24 hours. Secondary endpoints included evaluation of additional doses proximal to a repeat potassium level, magnitude of potassium reduction within 24 hours after potassium binder administration, discontinuation of agents known to cause hyperkalemia, and management of hyperkalemia per or off hospital protocol. RESULTS: One hundred and twenty-five patients from each arm were included in the primary and secondary endpoint analysis. The primary endpoint occurred in 44% of patients from the SZC arm compared to 40% from the SPS arm (P=0.608). Additional doses prior to and after a repeat potassium level were higher in the SZC arm compared to the SPS arm (32% vs. 4%, P=0.0001;53.6% vs. 32.8%, P=0.0014). There were no statistically significant differences in the remaining secondary endpoints. CONCLUSIONS: In this retrospective evaluation, SZC and SPS containing regimens were found to be equivalent. Further evaluation is needed to determine which potassium binder is the most operationally efficient and cost effective for acute hyperkalemia.