Elevated Creatinine Research Articles

Outcomes of Donation After Circulatory Death (DCD) and Ex-Vivo Lung Perfusion (EVLP) Lung Transplantation

BackgroundDonation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). ResultsThe study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001).After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality.On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) ConclusionStudy findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

Abdominal Gynecologic Procedures in Pancreas Transplant Recipients.

With the growing population of pancreas transplant recipients followed long-term, some female recipients are going to require surgical intervention for gynecologic symptoms and pathologies. Currently, there is a lack of literature describing how to approach this population and whether pelvic gynecologic procedures (GYN) can be performed safely given the proximity of the pancreatic (and possibly renal) allograft. In this single-center retrospective analysis, all pancreas transplant recipients that subsequently underwent GYN were reviewed. Subjects were identified by cross-referencing all pancreas transplants performed between January 2003 and December 2022 for any subsequent GYN. Demographics at transplant and GYN, indications and procedure performed, operative time, presence and involvement of a transplant surgeon, complications length of stay, and readmissions were reviewed. Seventeen patients who underwent a total of 19 GYN after pancreas transplantation were identified. Operations performed included tubal ligation (n=2), total abdominal hysterectomy with (n=6) or without bilateral salpingectomy (n=2), oophorectomy versus cyst drainage (n=2), bilateral oophorectomy (n=1), and unilateral (n=4) versus bilateral (n=2) salpingectomy. Four were performed through an open laparotomy and 15 were performed laparoscopically. In 11 cases, a transplant surgeon was involved intra-operatively. Eight of the 17 patients developed post-operative complications including post-operative fevers, fluid overload, neutropenia, elevated creatinine (n=2), nephrolithiasis, urinary tract infection, and incisional hernia. Five required readmission. GYN can be performed safely following pancreas transplantation, but careful planning and the involvement of the transplant surgery team are advised.

Clinical phenotype of ARDS based on K-means cluster analysis: a study from the eICU database

PurposeTo explore the characteristics of the clinical phenotype of ARDS based on Machine Learning. MethodsThis is a study on Machine Learning. Screened cases of acute respiratory distress syndrome (ARDS) in the eICU database collected basic information in the cases and clinical data on the Day 1, Day 3, and Day 7 after the diagnosis of ARDS, respectively. Using the Calinski-Harabasz criterion, Gap Statistic, and Silhouette Coefficient, we determine the optimal clustering number k value. By the K-means cluster analysis to derive clinical phenotype, we analyzed the data collected within the first 24 hours. We compared it with the survival of cases under the Berlin standard classification, and also examined the phenotypic conversion within the first 24 hours, on day 3, and on day 7 after the diagnosis of ARDS. ResultsWe collected 5,054 cases and derived three clinical phenotypes using K-means cluster analysis. Phenotype-I is characterized by fewer abnormal laboratory indicators, higher oxygen partial pressure, oxygenation index, APACHE IV score, systolic and diastolic blood pressure, and lower respiratory rate and heart rate. Phenotype-II is characterized by elevated white blood cell count, blood glucose, creatinine, temperature, heart rate, and respiratory rate. Phenotype-III is characterized by elevated age, partial pressure of carbon dioxide, bicarbonate, GCS score, albumin. The differences in ICU length of stay and in-hospital mortality were significantly different between the three phenotypes (P<0.05), with phenotype I having the lowest in-hospital mortality (10%) and phenotype II having the highest (31.8%). To compare the survival analysis of ARDS patients classified by phenotype and those classified according to Berlin criteria. The results showed that the differences in survival between phenotypes were statistically significant (P<0.05) under phenotypic classification. ConclusionsThe clinical classification of ARDS based on K-means clustering analysis is beneficial for further identifying ARDS patients with different characteristics. Compared to the Berlin standard, the new clinical classification of ARDS provides a clearer display of the survival status of different types of patients, which helps to predict patient prognosis.

Lambda light chain - restricted non - crystalline proximal tubulopathy with cast nephropathy in multiple myeloma: a case report and literature review

BackgroundMultiple myeloma (MM) often causes renal tubular damage, such as the light chain cast nephropathy (LCCN) and the light chain proximal tubulopathy (LCPT). The excessive light chains deposited in the proximal and distal tubules usually manifest with different characteristics, leading to a rare coexistence of the two pathological conditions. Here we report a unique case of a patient with multiple myeloma (MM) who presented with acute kidney injury (AKI) due to dual conditions of λ light chain-restricted non-crystalline LCPT and LCCN. This report reviews the clinical presentation and histological findings, comparing them with previously published cases.Case presentationA 49-year-old male patient was admitted with a chief complaint of “fatigue, loss of appetite for 40 days and elevated blood creatinine for 10 days.” In serum and urine, the λ light chain level and the ratio of κ to λ free light chain were 1235 mg/dl and 93.25 mg/dl, 0.0022 and 0.0316, respectively. Additionally, serum protein electrophoresis showed an M-spike with monoclonal IgD-λ. Bone marrow puncture revealed 30.5% primitive naive plasma cells, indicative of IgD-λ MM. Light microscopy of kidney biopsy specimen showed periodic acid-Schiff (PAS)-negative cytoplasm in some proximal tubules and PAS-negative casts with a rigid appearance in some distal tubule lumens. On immunofluorescence, these proximal tubular epithelial cells cytoplasm and casts stained exclusively with λ-light chains. Electron microscopy did not reveal any crystalline inclusions. Given the clinical and bone marrow puncture findings, the overall pathological presentation was LCPT with LCCN secondary to IgD-λ MM. After chemotherapy and dialysis, the patient’s condition was improved and he was tracked in follow-ups.ConclusionIn some tubular renal injuries caused by MM, the morphological changes are subtle and often overlooked. In this paper, we present a rare case of LCPT with LCCN showing λ restriction in patient with MM. Through the clinicopathological analysis of patients, the understanding of the disease can be deepened and the diagnosis rate improved.

Toxicological evaluation of anti-cough herbal tea made from aqueous extracts of G. Kola, C. Citratus and B. pinnatum

Background: Herbal formulations currently contribute significantly to medical remedies with varying effects on health indices. Garcinia kola seeds, Cymbapogon citratus, and Bryophyllum pinnantum leaves are among the widely used in herbal formulations. Objectives: This study evaluated the toxicological effects of the ternary combination of these plant materials on some renal, hepatic, hematological and histological parameters of streptococci-infected white albino rats. Materials and Methods: Samples of Garcinia kola seeds, Cymbapogon citratus leaves, and Bryophyllum pinnantum leaves were sourced locally and authenticated by a taxonomist. Aqueous extract of the ternary combination comprising of 40% G. kola, 30% C. citratus, and 30% B. pinnantum was prepared and administered on albino rats. Thirty five white albino rats grouped into 7 groups comprising of normal control, treatment control, disease control, and test group were used for the evaluation after a 14 days treatment on infected and uninfected rats. The rats were sacrificed, and samples collected. Some renal, hepatic, histological, and hematological indices were analyzed. Results: Comparison of all hematological parameters (except for platelet count) between uninfected-untreated and unifected-treated with extract showed no significant (p&gt;0.05) difference. Platelet count was significantly (p&lt;0.05) raised in all groups treated with the extract. Comparison control and the extract-treated group showed no significant (p&gt;0.05) difference in renal parameters indicating no adverse effects on renal function. However, comparison of parameters between control and the infected-treated group showed significantly elevated creatinine which alone may not be sufficient to support renal damage. Albumin, and total bilirubin were significantly (p&lt;0.05) lower in the extract-treated group compared to the control group. In contrast, total protein and globulin were significantly (p&lt;0.05) higher in the controls to the infected groups. ALT and AST were significantly (p&lt;0.05) lower in the extract treated groups compared to the control group. Although comparison of ALP activity between uninfected-untreated and infected-treated group showed significant (p&lt;0.05) elevation this alone may not be sufficient to support liver damage. The hematoxyline and eosine stained sections of the kidney and the liver tissues of the tea fed groups show normal kidney and liver histology. There was no significant change in the liver and kidney histology of the test and control groups. The extract did not cause adverse impact on these organs. Conclusion: Ternary combination of 40% G. kola, 30% C. citratus, and 30% B. pinnantum can effectively be used in treatment of cough without significant adverse effects on renal, hepatic, hematological and histological parameters. The ternary combination rather demonstrated significant hepato-protective feature.

Finerenone Improves Outcomes in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction Irrespective of Age: A Prespecified Analysis of FINEARTS-HF.

Background: Finerenone improves outcomes in patients with HF and mildly reduced or preserved ejection fraction (HFmrHF/HFpEF). It is important to understand the efficacy and safety of finerenone in these patients according to age. Methods: The aim of this analysis was to evaluate the interaction between age and the efficacy and safety of finerenone in the FINEARTS-HF trial (Finerenone trial to investigate efficacy and safety compared to placebo in patients with heart failure). A total of 6,001 patients aged 40-97 years were stratified by quartile (Q 1-4) of baseline age: Q1 40-66 years (n=1,581), Q2 67-73 years (n=1,587), Q 3 74-79 years (n=1,421), and Q4 ≧ 80 years (n=1,412). FINEARTS-HF evaluated the impact of age on the efficacy of finerenone with respect to the primary composite outcome of cardiovascular death and total (first and recurrent) HF events, including HF hospitalization or urgent HF event, along with secondary efficacy and safety outcomes. Results: The incidence of primary outcome increased with age. Finerenone reduced the risk of the primary outcome consistently across all age categories: RR (95% CI) Q1 0.70 (0.53- 0.92), Q2 0.83 (0.64-1.07), Q3 0.98 (0.76-1.26), and Q4 0.85 (0.67-1.07); p for interaction =0.27. Similarly, a consistent effect was observed for the components of the primary outcome. The mean increase in Kansas City Cardiomyopathy Questionnaire-total symptom score from baseline to 12 months was greater with finerenone than placebo, with a consistent effect across all age categories: mean placebo-corrected change (95% CI) Q1 2.87 (1.09-4.66), Q2 1.24 (-0.59-3.07), Q3 0.94 (-0.98-2.86), and Q4 1.24 (-0.90-3.38); P-interaction=0.50. Adverse events were similar across all age categories. The odds of experiencing hypotension, elevated creatinine, or hyperkalemia (increased) or hypokalemia (decreased) related to finerenone did not differ by age. Conclusions: In the FINEARTS-HF trial, finerenone reduced the primary outcome and components of the primary outcome, and improved symptoms across a wide age spectrum. In addition, finerenone was safe and well-tolerated, irrespective of age. Trial Registration: URL: https://clinicaltrials.gov Unique Identifiers: NCT04435626 and EudraCT 2020-000306-29.

Time to recovery from severe community-acquired pneumonia and its determinants among older adults admitted to North Wollo hospitals: A multi-centred cohort study.

Severe community-acquired pneumonia presents a looming threat to older adults globally, often resulting in alarming mortality rates. Despite advancements in treatment, challenges persist, exacerbated by factors like increasing comorbidity. As age rises, so does the risk of mortality and prolonged recovery periods. Particularly in low-income countries such as Ethiopia, the burden of severe community-acquired pneumonia is staggering. Yet, research on the estimated time to recovery and its determinants among older adults in this region remains insufficient, demanding urgent attention. Hence, in this study we endeavour to uncover insights into the recovery time and contributing factors among older adults. We conducted a multi-centred retrospective cohort study among 422 older adults aged >65 years. We collected data using a structured checklist, and the final sample was meticulously selected using a systematic sampling technique. We computed Kaplan-Meier survival curves and log-rank tests to compare survival curves. We assessed multicollinearity using variance inflation factors. Further, we employed a Cox regression model to identify significant determinants, with model fitness evaluated using a Cox-Snell residual plot. Statistical significance was declared at a P ≤ 0.05. In this study, 79.3% (95% confidence interval (CI) = 75.58-83.29) of patients achieved recovery, with a median time to recovery from severe community-acquired pneumonia of 19 days. Age >75 years, diabetes mellitus, chronic obstructive pulmonary disease, elevated creatinine level and baseline white blood cells greater than 11.0 × 109/L were found to be significant determinants. On average, older adults take 19 days to recover from severe community-acquired pneumonia. Recovery times are notably longer for individuals aged >75 years, those with comorbidities, and those with elevated white blood cell and creatinine levels. Therefore, tailored interventions addressing these specific factors could potentially improve patient outcomes.

Biomarker-based acute kidney injury sub-phenotypes refine risk assessment in children undergoing cardiac surgery.

Pediatric cardiac surgery-associated acute kidney injury (CS-AKI) is common with variable association with outcomes, possibly because transient serum creatinine (SCr) elevations are unrelated to kidney disease. Sub-phenotypes of CS-AKI with biomarker integration may provide prognostic enrichment. This study aims to determine if combining early postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr into sub-phenotypes strengthens associations with AKI and outcomes. We hypothesized that patients with early subclinical (uNGAL + , SCr -) or damage (uNGAL + , SCr +) CS-AKI would have more postoperative day 2-4 KDIGO-defined AKI and worse clinical outcomes than patients with early functional AKI (uNGAL - , SCr +). Two-center prospective observational study evaluating combinations of early uNGAL (8-12h from ICU admission, ≥ 150ng/mL) and early postoperative (≤ 8h of admission) KDIGO SCr-defined AKI to predict CS-AKI on postoperative days (POD) 2-4. Four CS-AKI phenotypes were derived (uNGAL - /SCr - ; uNGAL + /SCr - ; uNGAL - /SCr + and uNGAL + /SCr +). The primary outcome was POD2-4 KDIGO SCr-defined CS-AKI. Secondary outcomes included ventilator and intensive care unit-free days (maximum 28). Four hundred seventy-six patients (median age 4.8 [IQR 1.4-30.4] months, 39% female) were included. POD2-4 AKI occurred in 44 (9.2%). 27% were uNGAL + /SCr - and 0.4% (n = 2) uNGAL + /SCr + . The adjusted odds of POD2-4 AKI was ninefold higher (aOR: 9.09, 95%CI: 3.84-21.53) in uNGAL + /SCr - when compared to uNGAL - /SCr - . uNGAL + /SCr - was associated with fewer ventilator-free (aOR: 0.30, 95%CI: 0.19-0.48) and ICU-free days (aOR: 0.41, 95%CI: 0.26-0.66) when compared to uNGAL - /SCr - . Early postoperative uNGAL, regardless of SCr elevation, refines risk assessment for pediatric POD2-4 CS-AKI and associated morbidity, enabling earlier AKI identification and prognostics.

Cardioprotective action of apocynin in isoproterenol‐induced cardiac damage is mediated through Nrf‐2/HO‐1 signaling pathway

AbstractThis investigation evaluated the therapeutic benefit of apocynin in isoproterenol (ISO)‐induced cardiac damage in rats. ISO‐administered male Wistar rats were treated with apocynin for 2 weeks. Blood plasma and left ventricle of heart tissues were collected and analyzed for oxidative stress‐related parameters such as malondialdehyde (MDA), advanced oxidation protein product (AOPP), and nitric oxide (NO). The activities of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase were also measured. The gene expressions of oxidative stress‐related proteins such as Nrf‐2, HO‐1, and HO‐2 in cardiac tissues were also measured. In silico studies like molecular docking and molecular dynamics were also performed to detect how apocynin interacts with NADPH and nitric oxide synthase at the molecular level. This investigation revealed significant elevation of serum transferase enzymes and creatinine kinase‐Muscle Brain (CK‐MB) activities in ISO‐administered rats compared to the control. Apocynin effectively normalized the serum transferases and CK‐MB activities in the blood of ISO‐stressed rats. Moreover, ISO‐induced elevations of MDA, NO, and AOPP levels were also suppressed by apocynin treatment. Consistently, apocynin restored the reduced SOD and catalase activities in ISO‐administered rats. This restoration of enzyme activity might be due to the increased expression of Nrf‐2 and HO‐1 and reduced expression of iNOS and TNF‐α in ISO‐administered rats. Histological analysis revealed that apocynin treatment ameliorated the mononuclear cell adherence and fibrosis in the cardiac tissue of ISO‐administered rats. Computational studies also support the experimental findings. This study demonstrates that apocynin prevents ISO‐induced cardiac injury not only by preventing inflammation but also by empowering the antioxidant defense system.

Assessment of liver and kidney function in patients with ankylosing spondylitis on long-term non-steroidal anti-inflammatory drug therapy.

This study aimed to analyze the status of liver [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and kidney (serum creatine) function in ankylosing spondylitis (AS) patients assuming continuously non-steroidal anti-inflammatory drugs (NSAIDs) alone over a long period. Between 2013 and 2022, there were records of 385 AS patients. Of them, 56 were receiving only NSAIDs, and the files of these patients were retrospectively analyzed. Demographic and clinical characteristics were collected. Blood tests, including serum creatinine, AST, and ALT, were assessed at each visit. Of the 56 patients, 39 were male. The mean age was 45.30 years, and the follow-up period was 9.80 years. Of them, 44.6% used indomethacin, 26.8% naproxen, 17.9% diclofenac, 5.4% acemethazine, 3.6% meloxicam, and 1.8% celecoxib. The mean baseline serum creatinine was 0.71 mg/dL. The mean baseline serum AST and ALT were 19.6 u/L and 22.9 u/L, respectively. Baseline creatinine, AST, and ALT were not statistically significantly different between sexes. There was a statistically significant difference between mean creatinine concentrations at baseline and at year 3. One patient on naproxen discontinued treatment due to elevated creatinine. The creatinine level decreased during the patient's follow-up. Liver enzymes above 3 times the normal value were not seen in any patient. Based on real-world data, long-term use of NSAIDs has generally not led to acute liver and kidney injury or progressive impairment of hepatorenal function requiring discontinuation of treatment.

Acute Kidney Injury and Its Association With Dementia and Specific Dementia Types: Findings From a Population-Based Study in Sweden.

Preclinical studies suggest that acute kidney injury (AKI) results in biochemical and pathologic changes in the brain. We aimed to explore the association between experiencing AKI and subsequent risks of developing dementia. We conducted a study involving individuals aged 65 years and older in Stockholm from 2006 to 2019, who were free from dementia diagnosis and had data on kidney function. The exposure was an episode of AKI (time varying), ascertained by issued clinical diagnoses and transient creatinine elevations according to Kidney Disease Improving Global Outcomes criteria. The outcome was all-cause dementia and specific types of dementia, ascertained by clinically confirmed cases in the Swedish registry of cognitive/dementia disorders, the presence of 2 issued dementia diagnoses in outpatient care, or initiation of specific antidementia medications. We investigated associations with dementia through Cox proportional hazard regression by AKI, severity levels of AKI, AKI recurrence, and setting (community-acquired or hospital-acquired AKI). We included 305,122 individuals with a median age of 75 ± 8 years (56.6% women). During a median follow-up of 12.3 (interquartile range 8.7-13.3) years, there were 79,888 individuals (26%) suffering from at least 1 episode of AKI and 47,938 incident cases (16%) of dementia. The rate of dementia cases was 37.0 per 1,000 person-years (95% CI 36.2-37.8) after developing AKI, which was approximately 2 times higher than the rate observed during the periods before AKI (17.3, 95% CI 17.2-17.5). After multivariable adjustment, developing AKI was associated with a 49% higher rate of subsequent dementia (adjusted hazard ratio hazard ratio [HR] 1.49, 95% CI 1.45-1.53). This pattern was consistent across dementia types, with HRs of 1.88 (95% CI 1.53-2.32), 1.47 (1.38-1.56), and 1.31 (1.25-1.38) for dementia with Lewy bodies and Parkinson disease with dementia, vascular dementia, and Alzheimer dementia, respectively. Risk associations were stronger in magnitude across more severe AKIs and in hospital-acquired vs community-acquired AKI. Individuals who experienced an AKI were at increased risk of receiving a diagnosis of dementia.

A comparative study of femoral artery and combined femoral and axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation patients.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a critical support technique for cardiac surgery patients. This study compares the outcomes of femoral artery cannulation vs. combined femoral and axillary artery cannulation in post-cardiotomy VA-ECMO patients. This study aimed to compare the clinical outcomes of critically ill patients post-cardiac surgery under VA-ECMO support using different cannulation strategies. Specifically, the focus was on the impact of femoral artery (FA) cannulation vs. combined femoral artery and axillary artery (FA+AA) cannulation on patient outcomes. Through a retrospective analysis, we compared 51 adult patients who underwent cardiac surgery and received VA-ECMO support based on the cannulation strategy employed-FA cannulation in 27 cases vs. FA+AA cannulation in 24 cases. The FA+AA group showed significant advantages over the FA group in terms of the incidence of chronic renal failure (CRF) (37.50% vs. 14.81%, p = 0.045), preoperative blood filtration requirement (37.50% vs. 11.11%, p = 0.016), decreased platelet count (82.67 ± 44.95 vs. 147.33 ± 108.79, p = 0.014), and elevated creatinine (Cr) levels (151.80 ± 60.73 vs. 110.26 ± 57.99, p = 0.041), although the two groups had similar 30-day mortality rates (FA group 40.74%, FA+AA group 33.33%). These findings underscore that a combined approach may offer more effective hemodynamic support and better clinical outcomes when selecting an ECMO cannulation strategy. Despite the FA+AA group patients presenting with more preoperative risk factors, this group has exhibited lower rates of complications and faster recovery during ECMO treatment. While there has been no significant difference in 30-day mortality rates between the two cannulation strategies, the FA+AA approach may be more effective in reducing complications and improving limb ischemia. These findings highlight the importance of individualized treatment strategies and meticulous monitoring in managing post-cardiac surgery ECMO patients.

Safety of remdesivir in the treatment of acute SARS-CoV-2 infection in pediatric patients

BackgroundTransaminase and creatinine elevations have been well described in adults treated with remdesivir for COVID-19. It is hypothesized that a similar safety profile exists in children with COVID-19 treated with remdesivir, but available data are limited, especially in children < 12 months. The primary aim of this study was to determine the prevalence and timing of elevations in transaminases and creatinine in children with COVID-19 who were treated with remdesivir.MethodsThis was a retrospective, observational cohort study including all pediatric patients admitted to a single, freestanding children’s hospital who were positive for COVID-19 and received at least 1 dose of remdesivir between 1/1/2020 and 5/31/2022. Available baseline and peak transaminase and creatinine concentrations were evaluated. Multivariable logistic regression analysis was performed to identify risk factors for transaminase elevation.ResultsA total of 180 patients met inclusion criteria. Creatinine elevation of any grade was noted in 16% and remained elevated only in those with underlying chronic kidney disease. Transaminase elevation of any grade was noted in 58% of patients and remained elevated in only 1%. Older age and critical respiratory disease were associated with higher risk of significant transaminase elevation, whereas non-Hispanic ethnicity was strongly associated with protection against significant transaminase elevation.ConclusionsIn our cohort of hospitalized children with COVID-19 who were treated with remdesivir, most patients experienced only mild transaminitis and normal creatinine concentrations. A limited number of patients experienced laboratory abnormalities which were transient, suggesting a favorable safety profile for remdesivir use in pediatrics.

A Multi-Pathogen Retrospective Study in Patients Hospitalized for Acute Gastroenteritis.

Acute gastroenteritis (AGE) is a gastrointestinal tract disease often caused by consuming food or water contaminated by bacteria, viruses, or parasites, that can lead to severe symptoms requiring hospitalization. A retrospective study on patients admitted for AGE between 2021 and 2023 at the Pediatrics and Infectious Diseases Departments of Lecce Hospital was conducted. Demographic characteristics, year and month of admission, length of hospital stay, etiological agents, co-infections, and blood chemistry data of patients were collected. The study included 103 patients ranging in age from 0 to 15 years, with 58.25% being male. A total of 78 bacterial, 35 viral, and 7 parasitic infections were identified. The most commonly detected pathogens were Escherichia coli (38.83%), Norovirus (28.16%), Campylobacter jejuni (22.33%), and Salmonella typhi/paratyphi (10.68%). Only a few cases of Cryptosporidium (5.83%) were identified. Additionally, 17 co-infections (16.50%) were detected. Viral infections are the primary cause of hospitalization for AGE in children <5 years, while bacterial infections are more common among older patients. The significantly higher number of children <5 years old with elevated creatinine compared to children ≥5 years suggested that young children are more susceptible to dehydration than older children. Few cases of AGE were attributed to pathogens for which a vaccine has already been licensed. AGE is a serious health concern that could be effectively prevented by implementing food-based and community-level sanitation systems, as well as by increasing vaccination coverage of available vaccines and developing new effective and safe vaccines.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

Phase II Clinical Chemoprevention Trial of Weekly Erlotinib before Bladder Cancer Surgery.

We performed a clinical trial in non-muscle invasive urothelial cancer (NMIUC) patients randomized (2:1) to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib or placebo (either orally once weekly x 3 doses prior to scheduled surgery) to assess for a difference in EGFR phosphorylation in tumor adjacent normal urothelium <24 hours post-study dose and tolerance of weekly erlotinib. Thirty-seven volunteers (6 female/31 male, mean age 70, 35 white/2 non-white) with confirmed or suspected NMIUC were enrolled into either erlotinib (n=24; 900 mg-13, 600 mg-11) or placebo (n=13). Immunohistochemical assessment of phosphorylated and total EGFR in adjacent normal urothelium (20 erlotinib; 9 placebo) or tumor (21 erlotinib and 11 placebo subjects) at study end observed no significant difference between those receiving erlotinib or placebo. This was also true for other assessed tissue biomarkers (phosphorylated ERK, ERK, e-cadherin, p53 and Ki67). Adverse events were more common, in a dose-related fashion, in participants receiving erlotinib, e.g. 38% experienced Grade 1 with rare grade 2 diarrhea and skin toxicity vs 8% in placebo. Clinically insignificant, but statistically significant (p=0.001) elevations in serum total bilirubin and creatinine were observed in erlotinib participants. Serum erlotinib and metabolite concentrations (OSI-420) confirmed compliance in all erlotinib subjects and did not significantly differ between the 600 and 900 mg doses. Despite compelling pre-clinical and clinical data for targeted EGFR inhibition in bladder cancer prevention, these data do not support the use of weekly erlotinib to prevent progression of NMI bladder cancer.

Innovation and Patenting Activities During COVID-19 and Advancement of Biochemical and Molecular Diagnosis in the Post- COVID-19 Era.

The COVID-19 pandemic is to escalate globally and acquire new mutations quickly, so accurate diagnostic technologies play a vital role in controlling and understanding the epidemiology of the disease. A plethora of technologies acquires diagnosis of individuals and informs clinical management of COVID. Some important biochemical parameters for COVID diagnosis are the elevation of liver enzymes, creatinine, and nonspecific inflammatory markers such as C-reactive protein (CRP) and Interleukin 6 (IL-6). The main progression predictors are lymphopenia, elevated D-dimer, and hyperferritinemia, although it is also necessary to consider LDH, CPK, and troponin in the marker panel of diagnosis. Owing to the greater sensitivity and accuracy, molecular technologies such as conventional polymerase chain reaction (PCR), reverse transcription (RT)-PCR, nested PCR, loop-mediated isothermal amplification (LAMP), and xMAP technology have been extensively used for COVID diagnosis for some time now. To make so many diagnostics accessible to general people, many techniques may be exploited, including point of care (POC), also called bedside testing, which is developing as a portable promising tool in pathogen identification. Some other lateral flow assay (LFA)-centered techniques like SHERLOCK, CRISPR-Cas12a (AIOD-CRISPR), and FNCAS9 editor limited uniform detection assay (FELUDA), etc. have shown auspicious results in the rapid detection of pathogens. More recently, low-cost sequencing and advancements in big data management have resulted in a slow but steady rise of next-generation sequencing (NGS)-based approaches for diagnosis that have potential relevance for clinical purposes and may pave the way toward a better future. Due to the COVID-19 pandemic, various institutions provided free, specialized websites and tools to promote research and access to critically needed advanced solutions by alleviating research and analysis of data within a substantial body of scientific and patent literature regarding biochemical and molecular diagnosis published since January 2020. This circumstance is unquestionably unique and difficult for anyone using patent information to find pertinent disclosures at a specific date in a trustworthy manner.

The incidence and trends of proteinuria, azotemia and hypertension in cats receiving toceranib phosphate.

This retrospective study aimed to determine the incidence and trends of proteinuria, elevations in serum creatinine and urea, and systolic blood pressure in cats undergoing treatment with toceranib. In total, 32 cats treated with toceranib for malignancies were analyzed. Cats were included if urinalysis and urine protein:creatinine ratio (UPC) measurements were available at 28 days (T1) and 56 days (T2) after starting the treatment. Cats with concurrent lower urinary tract disease, including urinary tract malignancy, were excluded. Friedman's ANOVA compared variables between time points, and the Spearman test assessed the correlation between treatment duration and UPC. The median starting dose of toceranib was 2.68 mg/kg (range 1.7-3.9). In total, 15 (46.9%) cats received concurrent non-steroidal anti-inflammatory drugs. The most commonly treated tumors were oral squamous cell carcinoma (n = 10) and mast cell tumor (n = 5). None of the 32 cats developed progressive proteinuria or azotemia during the follow-up period (median 56 days; range 56-336). Notably, UPC and serum creatinine were significantly lower at T2 compared with baseline (P = 0.012 and 0.001, respectively). Among the four cats with baseline proteinuria, UPC decreased over time with or without concurrent telmisartan treatment (n = 2). All four of these cats experienced a reduction in tumor size with toceranib concurrently with their decreased UPC. There was no significant correlation between UPC and the duration of toceranib treatment (P = 0.089). Blood pressure was not significantly different over the assessed time points. The incidence of proteinuria, renal azotemia and hypertension in cats treated with toceranib for neoplasia appears to be low. Toceranib may be a viable treatment option even in cats with pre-existing proteinuria or renal disease, with careful monitoring of trends recommended.

Prophylactic and curative activity of Withania somnifera on experimentally induced calcium oxalate nephrolithiasis

Withania somnifera an ayurvedic herb was utilized to assess the antilithic properties of calcium oxalate (CaOx) Nephrolithiasis in rats fed ethylene glycol (EG) in an experimental setting. There were 5 groups of animals (n = 6). The control group was given normal saline, Lithiatic control was given ethylene glycol 1% (v/v) with ammonium chloride 1% (w/v) for 4 days (received stone inducing treatment till 28th day ), follow by 1% ethylene glycol alone in water, Standard group received antiurolithiatic drug (Cystone) (500 mg/Kg) from 15th day till 28th day, treatment group received Withania somnifera methanolic extract (200 mg/Kg) from 15th day till 28th day (Curative regimen) and received Withania somnifera methanolic extract (WS-200 mg/Kg) from 1st day till 28th day (prophylactic regimen) in wistar rats. Blood and kidney tissue were collected after the 28th day of urine. Ca2-, Mg2+, K+ and PO4- levels were estimated in urine, creatinine and urea level were estimated in serum whereas all oxidative stress was measured in kidney tissue. Additionally, Urinary microscopy and kidney histopathology were estimated. Lithiatic control group showed significant elevation (P&lt;0.0001 vs. control) in serum creatinine, blood urea and antioxidants levels. Due to crystal deposits, the histopathology of Lithiatic group showed tubule dilatation with interstitial inflammatory infiltrate, whereas the therapy group showed less tubule dilatation with interstitial inflammatory infiltrate. It can be concluded that at 200 mg/kg the herbal drug possessed significant potential in the management of nephrolithiasis.

Anti-OJ antibody-positive anti-synthetase syndrome following SARS-CoV-2 infection: a case report and literature review

BackgroundCOVID-19 can induce a systemic inflammatory response with variable clinical manifestations. Similar to various viruses, COVID-19 has been implicated in the pathogenesis of autoimmune diseases. This article highlights the potential for infections including the SARS-CoV-2 virus to induce exacerbations of pre-existing autoimmune diseases or even potentially unmask de novo autoimmune diseases in particular anti-synthetase syndrome (ASSD) in predisposed individuals. Although there are other case reports of ASSD following SARS-CoV-2 infection, here we present the first reported case of a gentleman with a newly diagnosed anti-OJ positive anti-synthetase syndrome following SARS-CoV-2 infection.Case presentationDescribed is a case of a 70-year-old man presenting to the emergency department with worsening dyspnea in the context of a recent COVID-19 infection. CT-chest revealed changes suggestive of fibrotic lung disease, consistent with usual interstitial pneumonitis (UIP) pattern. Despite recovery from his COVID-19 illness, the patient subsequently developed proximal myopathy with cervical flexion weakness on further assessment with persistently elevated creatinine kinase (CK). Myositis autoantibodies found a strongly positive anti-OJ autoantibody with MRI-STIR and muscle biopsy performed to further confirm the diagnosis. The patient received pulse methylprednisolone 1 g for 3 days with a long oral prednisolone wean and in view of multiple end-organ manifestations, loading immunoglobulin at 2 g/kg administered over two days was given. In addition, he was then commenced and escalated to a full dose of azathioprine given a normal purine metabolism where he remains in clinical remission to this date. At least 267 cases of rheumatic diseases has been associated with SARS-CoV-2 infection as well as COVID-19 vaccination. A literature search on PubMed was made to determine the amount of case reports describing myositis associated with SARS-CoV-2 infection. We found 3 case reports that fit into our inclusion criteria. Further literature searches on diagnostic approach and treatment of ASSD were done.ConclusionAlthough SARS-CoV-2 infection itself can cause a directly mediated viral myositis, this case report highlights the possibility of developing virus-triggered inflammatory myositis through multiple aforementioned proposed mechanisms. Therefore, further studies are required to explore the relationship and pathophysiology of SARS-CoV-2 infection and the incidence of inflammatory myopathies.