The factors associated with increased risk of hospitalisation in people with diabetes following SARS-CoV- 2 infection: A national replication study

Aim: People with type 1 or type 2 diabetes have a higher hospital admission rate following Covid-19 infection. This study aims to determine the degree to which the results of a previous study in Greater Manchester (GM) could be replicated in national-level data for England. Method(s): We focussed on the univariable regression analysis, which shows the association between admission and Covid-19 infection in people with diabetes. Modelling was conducted using logistic regression on data from the Covid-IMPACT database. Odds ratios were compared descriptively with the previous study. Result(s): In people with type 2 diabetes, factors associated with an increased risk of hospitalisation similar to the previous study were: older age, male sex, higher social deprivation, higher body mass index (BMI), higher cholesterol, lower eGFR, taking an ACE-inhibitor/ ARB, not taking metformin, and having asthma or hypertension. Patients with COPD, and those taking aspirin or clopidogrel also had increased risk, but the national data showed a greater risk (GM COPD odds ratio 1.89 [1.63-2.19] vs national 2.34 [2.28-2.40] / aspirin 1.49 [1.34-1.66] vs 1.66 [1.63-1.70] / clopidogrel 1.71 [1.47-1.98] vs 1.99 [1.94-2.04]). Similar results were observed in patients with type 1 diabetes. However, due to the increase in sample size, many factors which were previously not statistically significant have become significant, such as in type 2 diabetes BMI, low HDL-cholesterol. Conclusion(s): We have successfully replicated the methods, results and conclusions of our previous study in relation to factors associated with increased risk of hospital admission in diabetes individuals. Regional databases are suitable for large cohort studies, and in this instance produced similar results to a national database, validating our previous findings.

Health-related quality of life, mental health and caregiver burden in children with autosomal recessive polycystic kidney disease (ARPKD)

Objective: To examine whether established patient-reported outcome measures are suitable for capturing the impact of ARPKD in children and their families. Method(s): We assessed 44 children with ARPKD (40 families) with respect to patients' health-related quality of life ((hr- QOL) using PedsQLTM ESRD module) and mental health (strength and difficulties questionnaire (SDQ)) as well as family and caregiver burden (Impact on family score (IFS) und Ulm inventory of parental caregiver QOL (ULQIE)) and compared them to published data and 36 healthy control children matched for age and time. Result(s): Patients were aged 9.5 +/- 5.9 years (vs. controls 8.8 +/- 5.0, p = ns) and 21 (48%) were female (vs. 19 controls (53%), p = ns). Mean eGFR was 81 ml/min*1.73m2 (range 4 - 165);7 received dialysis and 11 had functioning kidney transplants (KTX, 2 combined with liver transplants). Eight patients had developmental delay secondary to medical complications, while chronic illness was an exclusion criterion for healthy controls. 61 caregivers of affected children had same gender-distribution (61% vs. 60% mothers) and age (both 42 +/- 7 years) and number of dependent children (1.8 +/- 0.9 vs. 2.0 +/- 0.8) as 57 caregivers of healthy children. The mean proxy reported PedsQL Total score was 77.5 +/- 10.6 (range 59 - 96). It correlated significantly to eGFR (r = 0.5, p < 0.01, (also within the subpopulations pre- and post-KTX)). Parents reported greater mental health problems in affected than in control children with a higher SDQ total score mainly due to higher scores in the hyperactivity and peerinteraction subscales. ULQIE revealed that parents of affected children had significantly lower levels of physical functioning, self-fulfillment and general QOL, but despite higher emotional burden scores they indicated similar satisfaction with family life. Impact on family scores were in a similar range to those of children with moderate to severe disabilities. Conclusion(s): The good spread of PedsQLTM ESRD-scores and their correlation to renal function indicates that it captures significant aspects of ARPKD, however, it may need further adjustment to include liver complications. All four chosen instruments revealed significant impact of ARPKD on hrQOL and mental health of affected children as well as family life and parental wellbeing in comparison to healthy controls. More problems with peer-interactions may also be due to more stringent shielding of chronically ill children from social contacts during the COVID pandemic compared to healthy children.

Ai-Based Prediction of Lung Tissue Involvement Is Predicitive of Covid-19 Severity

Background: During COVID-19 epidemics several artificial-intelligence neural networks (ANN) systems were developed classify the risk of disease progression to respiratory failure and death, providing aid for clinical decision. However, for optimal results these models should link multiple medical data in a simple model. In this study we analyse the in-hospital mortality and mechanical ventilation risk using combination ANN based rapid computed tomography assessment tool and selected clinical variables. Method(s): Data of 4317 COVID-19 hospitalized patients including 266 cases required mechanical ventilation were analysed using newly constructed and locally trained ANN algorithm. Demographic, clinical, laboratory, and ANNbased lung inflammation data were analysed using proportional Cox Hazards model and estimate in-hospital mortality and intensive care admission risk. Result(s): Overall in-hospital mortality associated with ANN-assigned percentage of the lung involvement (HR 5.72 (95%CI: 4.4-7.43), p< 0.001 for the patients with >50% of lung tissue affected by COVID-19 pneumonia), age category (HR 5.34 (95%CI: 3.32-8.59) for cases >80 years, p< 0.001), procalcitonin > 2 (HR: 2.1 (95%CI: 1.59-2.76) ng/ml p< 0.001, C-reactive protein level category (max. HR 2.11 (95%CI: 1.25-3.56) for CRP >100 mg/dL, p=0.004), estimated glomerular filtration rate (max HR 1.82 (95%CI: 1,37-2,42), p< 0.001 for eGFR < 30 ml/min) and troponin increase above upper limit normal level (HR: 2.14 (95%: 1.69-2.72, p< 0.001) (Figure 1). Furthermore, risk of mechanical ventilation also associated with ANN-based percentage of lung inflammation (HR 13.2 (8.65-20.4), p< 0.001 for patients with >50% involvement), age, procalcitonin > 2 ng/ml (HR: 1.91 (95%CI: 1.14-3.2), p=0.14 estimated glomerular filtration rate (HR 1.82 (1.2-2.74), p=0.004 for eGFR < 30 ml/min) but also clinical variables, including (HR: 2.5 (95%CI: 1.91-3.27), p< 0.001), cardiovascular and cerebrovascular disease (HR: 3.16 (95%CI: 2.38-4.2), p< 0.001), and chronic pulmonary disease (HR: 2.31 (95%CI: 1.44-3.7), p< 0.001). Conclusion(s): ANN-based lung tissue involvement was the strongest predictor of unfavorable outcomes in COVID-19, and represent valuable support tools for clinical decisions. (Figure Presented).

Rates of Hypoglycemia with Reduced- vs. Standard-Dose Insulin for Hyperkalemia Treatment in Renal Insufficiency

Objective: The primary objective was to assess the difference in rates of hypoglycemia (blood glucose (BG) <=70 mG/dL) when using reduced-dose (5 units) vs. standard-dose (10 units) of IV regular insulin for hyperkalemia treatment in renal insufficiency. Secondary objectives include the efficacy of insulin dose on potassium reduction and evaluating the difference in rates of severe hypoglycemia (BG <=54 mG/dL) between the groups. Method(s): This was a retrospective chart review of patients with renal insufficiency treated with IV regular insulin for hyperkalemia at a tertiary care teaching hospital from June 2020 to June 2021, with institutional review board approval. Inclusion criteria encompassed patients aged 18 years and older with elevated baseline potassium (>=5.5 mEq/L), estimated glomerular filtration rate < 30 mL/min/1.73m2, end stage renal disease, or presence of acute kidney injury, having received either 5 or 10 units of IV regular insulin for hyperkalemia, and had documented glucose and potassium levels after insulin administration. Patients who were pregnant, had diabetic ketoacidosis, or a baseline BG <=70 mG/dL were excluded. Data collection included patient demographics, diabetes history, relevant labs at time of elevated potassium, doses of insulin and dextrose administered for hyperkalemia treatment, presence of coronavirus-19 infection, glucose levels within 6 hours and first potassium level within 24 hours following insulin administration, concurrent use of potassium-lowering agents, insulin outside of hyperkalemia treatment, or steroids, and mortality. Result(s): Out of 409 patients included, 92 were in the 10-unit group and 317 in the 5-unit group. The rate of hypoglycemia in the 5-unit arm vs. the 10-unit arm was 6.9% vs. 8.7% (p=0.649), respectively. The rate of severe hypoglycemia between the 5-unit arm and the 10-unit arm was 3.2% vs 5.4% (p=0.682), respectively. The percent normalization of potassium was not statistically different between the 5-unit group and the 10-unit group (59% vs. 68%;p=0.115), with the same mean reduction in potassium from baseline (0.8 mEq/L (p=0.947)). Administration of concurrent treatments for hyperkalemia was similar between the groups, with dialysis being the only one with statistical significance in normalization of potassium. Patient characteristics that could have an impact on risk of hypoglycemia were studied and analyzed, including pre-treatment BG, history of diabetes mellitus, insulin naive, and patient weight. In patients with hypoglycemia (n=30) vs. those without hypoglycemia (n=379), there was a significantly different mean pre-treatment BG (113 mG/dL vs. 178 mG/dL, p<0.001). Discussion/Conclusion: There was no significant difference in rates of hypoglycemia and severe hypoglycemia between the 5-unit vs. 10-unit groups. There was no significant change in potassium normalization between the two insulin doses. Because of the small number of hypoglycemia events, larger studies are needed to better understand if 5 units of regular insulin is a safer option for the treatment of hyperkalemia in renal insufficiency.Copyright © 2023

Performance of a Computerized Insulin Infusion Protocol in 359 Critically Ill Patients with COVID-19

Objective: People with diabetes and uncontrolled hyperglycemia are at high risk of COVID-19 complications and as such, many patients admitted to the ICU with COVID-19 have diabetes or stress hyperglycemia. It is suggested that quick and adequate control of hyperglycemia without increasing the risk of hypoglycemia is imperative to improve outcomes in these patients. Control of wide fluctuations of glycemic variances in these patients may often require modifications of existing strategies of glycemic management. Use of a computerized insulin infusion protocol (CIIP) in these settings could be largely beneficial in getting early and sustained glycemic control. We report our experience with the Lalani Insulin Infusion Protocol (LIIP), a novel CIIP with dynamic and adaptive glycemic targets in accordance with the patient's glycemic state, in critically ill COVID-19 patients with hyperglycemia treated with IV insulin. Method(s): We conducted a retrospective analysis of 359 critically-ill COVID-19 patients in whom LIIP was used (8/18/2020 to 08/31/2022) at six HonorHealth Hospitals in the Phoenix metropolitan area. Primary endpoints of the analysis included Time to Euglycemia (min), % of time in euglycemia (70-180 mg/dl), % of time in hyperglycemia (>180 mg/dl), and % of time in hypoglycemia (<70 mg/dl). We also report the average length of stay (ALOS) in the hospital and ICU as well as the discharge dispositions of these patients. Result(s): Of the 359 critically ill COVID-19 patients who received IV insulin directed by LIIP, 167 patients had diabetes, 266 patients were treated with steroids, 226 patients had compromised renal function (eGFR< 60), 40 patients had sepsis, and 5 patients had cardiovascular comorbidities. The following glucometrics were observed: average Time to Euglycemia from baseline glucose values was 278 minutes, average % time in euglycemia was 83.01%, average % time in hyperglycemia was 16.77%, and average % time in hypoglycemia was 0.22%. Of the 359 patients, there were 166 deaths (46.2%), 91 patients were discharged to home (25.4%), and 102 patients were discharged to an interim facility (28.4%). The hospital ALOS was 15.02 days and ICU ALOS was 9.50 days. Discussion/Conclusion: For HonorHealth hospitals, LIIP was a safe and effective method of quickly achieving and maintaining euglycemia in critically ill patients with COVID-19, while maintaining low hypoglycemia incidence. Herein the patients reported had varying degrees of comorbidities and treatments, including steroids and vasopressors;however, no modifications in glycemic management strategy or nursing workflow were necessary during the use of LIIP due to its adaptive formula which individualizes IV insulin rates for each patient.Copyright © 2023

Pharmacokinetics Informs Remdesivir Dosing for Patients with Severe Renal Impairment

Background: Despite renal impairment (RI) being a risk factor for severe COVID-19, there are no approved antiviral treatment options for patients with severely impaired kidney function (eGFR less than 30 mL/min/1.73 m2 or kidney failure) in the US. At the time remdesivir (RDV) was initially approved for the treatment of COVID-19, the impact of renal impairment (RI) on pharmacokinetics (PK) of RDV, its metabolites, and the excipient, sulfobutylether beta-cyclodextrin sodium (SBECD), was not known. Method(s): Here, we report the PK data supporting dosing of RDV in COVID-19 patients with severely impaired kidney function. PK samples for RDV and metabolites (GS-704277, GS-441524) were collected in the Phase 3 REDPINE study in hospitalized COVID-19 patients with severely impaired kidney function. Participants in this double-blind study were randomized 2:1 to intravenous (IV) remdesivir (200 mg on Day 1, then 100 mg daily up to Day 5) or IV saline as placebo-to-match. SBECD PK was analyzed in a phase 1 study in non-COVID-19 participants with normal kidney function, mild and moderate RI who received 100 mg dose of remdesivir (containing 3000 mg SBECD). The population PK analysis included observations from healthy and COVID-19 patients with full range of renal function across all adult studies. Result(s): Geometric mean exposures (AUCtau) observed in REDPINE Study as compared to PINETREE Study increased up to 553% for the GS-441524 metabolite (dependent on renal elimination) and to a lesser degree GS-704277 (294%, minor renal elimination) and RDV (78.9%;an increase explained by factors other than renal function, namely, hospitalization and body weight) (Table 1). The increased PK exposures were not associated with new safety signals in this study (n=163 remdesivir, n=80 placebo). Population PK analysis identified baseline eGFR as a significant covariate for GS-704277 and GS-441524 clearance, but not for RDV itself. SBECD PK was characterized by short half-life (t1/2) (1.6 hours in normal renal function to 3.8 hours in moderate RI) and fast plasma clearance (7.9 L/h in normal renal function). Analysis of SBECD in severe RI (REDPINE) is ongoing, but accumulation is not expected based on its observed short plasma t1/2. Conclusion(s): Given the observed PK and the absence of any new safety signals associated with increased metabolite levels in patients with severely impaired kidney function, no dose adjustment is recommended for RDV in COVID-19 patients with eGFR < 30 mL/min/1.73 m2, regardless of the need for dialysis.

Evaluation of Urine L-FABP Point of Care Kit in the Philippines as Predictive Marker of Clinical Severity of COVID-19 (EPOCH COVID study)

Background: The search for simple clinical and laboratory markers to help predict the clinical severity of patients presenting with COVID-19 has prompted this study to look at the predictive value of urine L-FABP (Liver Type-Fatty Acid Binding Protein) point-of-care test kit at the initial presentation of COVID-19 patients to the hospital. Method(s): The validation study prospectively included 109 consecutive patients with mild to moderate COVID-19, mean age of 52.2 years (range 19-84) presenting at the Emergency Rooms of 4 participating Metro-Manila hospitals from February to April 2021, with available data for analysis for 103 patients. Urine L-FABP POC (Point-of-Care) test and other clinical parameters and the level of severity of COVID-19 were determined at Day 0, Day 4 and Day 7. Computations for Sensitivity, Specificity, Positive and Negative Predictive values and Likelihood ratios were performed Results: Twenty-three patients tested positive for urine L-FABP, out of the 103 patients analyzed, while 80 tested negative. Of the 23 patients who tested positive for urine L-FABP, 6 has progressed in severity, while 17 did not progressed. Of the 80 patients who tested negative for urine L-FABP, 13 progressed, while 67 did not progressed in severity. Giving a Sensitivity of 31.58%, Specificity of 79.76%, Positive predictive value of 26.09%, Negative predictive value of 83.75%. Combining urine L-FABP and initial clinical parameters like SIRS (Systemic Inflammatory Response Syndrome) criteria to predict progression of severity yielded a higher Specificity of 91.67 % and Negative Predictive value of 84.62%. Conclusion(s): The study shows the utility of initial urine L-FABP POC test as a negative screening test in triaging adult patients presenting to the ER with mild to moderate COVID-19. Patients at the ER with a negative urine L-FABP test, will most likely not progressed to severe COVID-19. Combining clinical parameters like SIRS Criteria with the urine L-FABP result can increase the negative predictive value.Copyright © The PHILIPPINE JOURNAL OF INTERNAL MEDICINE is a peer reviewed journal and a copyrighted publication of the Philippine College of Physicians.

Study immunity and genetic in Covid 19

The aim of this study was to determine the immue function of human leukocyte antigens and some vital indicators in Covid 19 patients. This study was conducted at Ibn Al-Khatib hospital, Baghdad. Sixty four blood sample of Covid 19 patients (32male and 32female patients), while healthy volunteers group 15 male and 15 female with age between 10 to 60. Level of IL-1b, CD4, WBC, ESR, Urea, sugar test, were measured,results showed a significant increase (P<0.01) in each measured of IL-1b, CD4, WBC, ESR, Urea, Sugar. The more infection of Covid 19 with some factors such as, smoking, chronic diseases. The measurement of the level of IL-1b, CD4 by means of the enzyme - linked immunosorbent assay (ELISA), and WBC, PLT, measurement method using ABX micros 60 hematology analyzer, Urea, Sugar semi-automated chemistry analyzer using Mindray BC-5000. The data was analyzed with Graph pad prism software. © 2023 Author(s).

Effect some parameter of immunity CD4 and IL1 in Covid 19

The aim of this study was to determine the immune function of human leukocyte antigens and some vital indicators in Covid 19 patients. This study was conducted at Ibn Al-Khatib hospital, Baghdad. Sixty four blood sample of Covid 19 patients (32 male and 32 female patients), while healthy volunteers group 15 male and 15 female with age between 10 to 60. Level of IL-1b, CD4, WBC, ESR, Urea, sugar test, were measured results showed a significant increase (P<0.01) in each measured of IL-1b, CD4, WBC, ESR, Urea, Sugar. The more infection of Covid 19 with some factors such as, smoking, chronic diseases. The measurement of the level of IL-1b, CD4 by means of the enzyme - linked immunosorbent assay (ELISA), and WBC, PLT, measurement method using ABX micros 60 hematology analyzer, Urea, Sugar semi-automated chemistry analyzer using Mindray BC-5000. The data was analyzed with Graph pad prism software. © 2023 Author(s).

Atrial fibrillation incidence in SARS-CoV-2 infected patients: Predictors and relationship with in-hospital mortality

Background: Among the different CardioVascular (CV) manifestation of the COronaVIrus-related Disease (COVID) particular attention has been paid to arrhythmia and particularly to Atrial fibrillation (AF). The aim of our study was to assess the incidence of AF episodes in patients hospitalized for COVID and to evaluate its predictors and its relationship with in-hospital all-cause mortality. Method(s): We enrolled 3435 cases of SARS-CoV2 infection admitted in four hospitals in Northern Italy. We collected data on clinical history, vital signs, Intensive Care Unit (ICU) admission, laboratory tests and pharmacological treatment. AF incident and all-cause in-hospital mortality were considered as outcomes. Result(s): 145 (4.2%) patients develop AF during hospitalization, with a median time of 3 days (IQR: 0, 11.5) from admission. Incident AF patients were older and had lower eGFR, lower platelet and lymphocytes count and higher C-Reactive Protein (CRP), were admitted more frequently to ICU and more frequently died compared to subjects that didn't present AF. At the Cox regression model significant determinants of incident AF were older age (HR 1.070;95% CI: 1.048, 1.092), history of AF (HR 2.800;95% CI: 1.465, 5.351), ischemic heart disease (HR 0.324;95% CI: 0.130, 0.811) and ICU admission (HR 8.030;95% CI: 4.511, 14.292). Incident AF was a predictor of all-cause mortality (HR 1.679;95% CI: 1.170, 2.410), together with age (HR 1.053;95% CI: 1.042, 1.065), dementia (HR 1.553;95% CI 1.151, 2.095), platelet count (HR 0.997;95% CI: 0.996, 0.999) higher CRP (HR 1.004;95% CI: 1.003, 1.005) and eGFR (HR: 0.991;95% CI: 0.986, 0.996) Conclusion(s): AF present as the main arrhythmia in COVID-19 patients and its development during the hospitalization strongly relates with in-hospital mortality.

Acute Kidney Injury after Covid 19 Infection in Chronic Kidney Disease Patients of Bangladesh: Retrospective Study

Introduction: COVID 19 pandemic has caused unprecedented devastation worldwide. Spectrum of Covid 19 illness is wide and variable. Risk of mortality is increased in chronic kidney disease patients, during coronavirus disease. CKD is an independent risk factor for poor outcome. AKI is also common in COVID-19 patients who are hospitalized. This study was undertaken to see the outcome of Covid-19 infection in CKD patients. Method(s): This retrospective observational study was carried out in the Kidney Foundation Hospital and Research Institute, Bangladesh from January 2021 to July 2022. One hundred CKD patients who were on regular follow up in the outpatient department and developed COVID-19 as confirmed by reverse transcription polymerase chain reaction (RT-PCR) test underwent chart review after they consented to be part of the study. Their clinical parameters, treatment regiments and laboratory investigations were noted in a data collection sheet. Data was analyzed by Statistical Analysis Software. Result(s): The mean age of the patients was 55.2 years. Of them 43% were female. Diabetes mellitus was the most common comorbidity, seen in 65% of the patients. 24% were CKD stage 4 or 5 prior to the onset of COVID-19, rest were of earlier stage. Hospitalization was required in 65.3% patients;41.1% required oxygen, steroid given in 19.8% patients,8.4% required ICU transfer. 7 patients died, all of respiratory failure. Treatment with antiviral, biologics like Tocilizumab and plasma exchange was not commonly done. AKI developed in 28% of the patients during the course of the illness. Males were more prone to develop AKI (p = 0.23). People with longer duration of symptoms had higher incidence of AKI (p < 0.0001). AKI incidence did not vary according to baseline eGFR (p = 0.16). Among those who developed AKI, 17.9% required temporary dialysis and 7.1% went on to develop end stage kidney disease. Interim outcomes such as hospitalization, oxygen requirement, ICU transfer and death did not vary according to development of AKI. Conclusion(s): People with chronic kidney disease and other comorbid conditions are at higher risk for more serious COVID-19 illness. In our study it has been shown that a significant proportion of CKD patients developed AKI after COVID 19 infection of which a number of patients develop end stage kidney disease and required renal replacement therapy. No conflict of interestCopyright © 2023

Frequent need for apixaban dose adjustment for atrial fibrillation in an unselected acute medical admission population during the COVID 19 pandemic

Background: During the COVID-19 pandemic, systematic switching patients of eligible patients with atrial fibrillation from warfarin to direct oral anticoagulants (DOACs) was encouraged to simplify drug dosing and obviate the need for regular monitoring. Regional exclusions to switching included mechanical heart valves, moderate to severe mitral stenosis and stage 5 chronic kidney disease (estimated glomerular filtration rate [eGFR]< 15ml/min/1.73m2). However, each DOAC requires dose adjustment depending on renal function and other patient factors. Purpose(s): Failure to dose reduce when indicated leads to excessive serum drug concentration and increased risk of major haemorrhage, particularly in patients who are acutely unwell. We thus quantified the likelihood of need for dose adjustment in an unselected acute medical admission population. Method(s): While on call, a single investigator prospectively identified all patients admitted on the acute medical or cardiology take-in between 1/ 12/21 and 1/2/22 who were taking apixaban for atrial fibrillation. Apixaban was selected as the study DOAC as it was the most commonly used DOAC but had the most complex dose adjustment algorithm and hence risk of dose error. In order to determine the appropriate drug dosage, patient age, weight, serum creatinine and eGFR were recorded. Dose reduction to 2.5mg was required if the patient meet 2 of the following 3 criteria of [age>80 years, weight <60kg, serum creatinine >133umol/l], or a single criterion, had an eGFR <30ml/min/1.73m2. Drug discontinuation was required if eGFR was <15ml/min/1.73m2. Result(s): All patients identified (n=50) had a CHA2DS2-VASc score of >=2. Patients with active COVID-19 infection were excluded. Mean age was 77.2 years (range 46-102). Mean weight was 78kg (range 52-101). Mean serum creatinine was 212umol/l (range 62-595). Mean eGFR was 33ml/min/1.73m2 (range 8 to >60). Of the 50 patients, 24 (48%) were taking the appropriate apixaban dose on admission which did not require dose adjustment (18 of whom were appropriately taking 5mg bd and 6 were taking 2.5mg bd). Dose reduction from 5mg bd to 2.5mg bd was required in 17 (34%) patients. Stopping treatment, at least temporarily due to eGFR<15ml/min/1.73m2, was indicated in 9 (18%) of patients. No patient required an increase in drug dose. (Graph 1) Conclusion(s): Over half of acute medical or cardiology patients admitted within a COVID-19 setting and taking apixaban for atrial fibrillation required at least temporary drug dose adjustment or discontinuation. Clinicians should expect that adjustment of apixaban dose may be required during acute admission.

Spectrum of Indication Kidney Biopsies in Community Acquired Aki

Introduction: Community acquired acute kidney injury (CA-AKI) in low income settings is different from that in the high income settings. Infections, poisoning, toxic envenomations and pregnancy related AKI are common. Kidney biopsy is seldom performed in these patients unless atypical clinical course or features are present. We have established a prospective cohort of patients with CA-AKI at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. We present the spectrum of kidney biopsies in patients who underwent kidney biopsy in this cohort. Method(s): The study is a single centre, prospective, observational cohort study of patients with CA-AKI at PGIMER. Patients aged >12 years and with a diagnosis of CA-AKI are eligible for enrolment. Patients with underlying CKD, urinary tract obstruction, COVID 19, malignancy or heart failure are excluded. Clinical and laboratory data are recorded at baseline. Follow up visits are scheduled at 1 and 4 months after hospital discharge. Kidney biopsies are done only in those patients who have atypical clinical course or features (e.g. persistent kidney dysfunction despite other clinical improvement, strong clinical suspicion of dominant glomerular involvement or interstitial nephritis etc.). We present the spectrum of histopathological diagnoses that were recorded in such patients till date. Result(s): Till now, 646 patients have been included in the cohort. The leading causes of CA-AKI are sepsis (52%), obstetric complications (14%), envenomation (8%), nephrotoxic drugs (6%) and poisons (3%) (figure 1). 18.4% patients had died after CA-AKI. At >=3 months after CA-AKI, 16.3% patients had not recovered completely with persistent eGFR <60 ml/min/1.73m2. 44 patients had undergone kidney biopsy in this cohort. Incomplete recovery, and clinical or diagnostic dilemmas were indications for doing kidney biopsy. The leading clinical diagnoses in this subgroup were sepsis (23%), nephrotoxic drugs (23%), envenomation (9%), obstetric causes (6.8%) and others (25%). Acute interstitial nephritis, acute tubular necrosis and acute cortical necrosis were most common histologic diagnoses (table 1). Combinations of various histologic features were not uncommon. Pigment casts were recorded in 13 patients. 4 patients had acute cortical necrosis, 2 being after post-partum AKI and one each due to acute gastroenteritis and unknown animal bite. Glomerular involvement were recorded in 8 patients (table 1). Thrombotic microangiopathy was present in 4 patients. In this subgroup of patients who underwent kidney biopsy, 3 (7%) had died and 8 (18%) had eGFR <60 ml/min/1.73m2 at >=3 months. Figure 1: Causes of CA-AKI in patients [Formula presented] Table 1: Histologic diagnoses in kidney biopsies in CA-AKI cohort. [Formula presented] Conclusion(s): Acute interstitial nephritis and acute tubular necrosis, alone or in combination with other findings, were the most common histologic diagnoses in indication kidney biopsies in CA-AKI. Adverse outcomes (mortality or progression to CKD) are common after CA-AKI. No conflict of interestCopyright © 2023

Accommodating ''History Effects'' in Long Duration, Multisite Clinical Trials to Ensure Relevant and Compelling Evidence

Over the course of a clinical trial, changes in the practice environment have the potential to reduce internal and external validity and impact change in patient outcomes. Such ''history effects''1 can take the form of changes in standard of care, clinical guidelines and recommendations, new drug/device availability in the marketplace, testing and screening procedures, and, as recently experienced, a global pandemic. Clinical trials conducted over many years are particularly susceptible to history effects. Such effects can impact foundational ability to continue a trial, including clinician equipoise and ability to implement trial interventions, necessitating awareness and action planning. For example, Curtis et al.2 acknowledged challenges with clinical guideline history effects and issued recommendations for addressing them such as consideration of participant wellbeing, stakeholder engagement, safety monitoring, review of guideline and policy changes, and development of rules for protocol changes. This session will explore how four multisite clinical trials conducted with VA Cooperative Studies Program sponsorship and coordination have weathered history effects during prolonged periods of enrollment. Topics to be covered include the implementation of pragmatic designs, monitoring of clinical guidelines, assessing control group treatment conditions, modifying protocols, adjusting quality assurance procedures, refining recruitment pathways, and training site investigators. The speakers, Study Chairs, will describe best practices and provide recommendations for navigating history effects in prolonged multisite clinical trials that can ensure outcomes remain relevant and compelling to inform public health at trial commencement. The CSP 2008/PTXRx study is a pragmatic, randomized, double-blind, placebo-controlled, multicenter clinical trial of Veteran patients with diabetic kidney disease (DKD) examining whether pentoxifylline (PTX), when added to usual care, can delay time to end-stage renal disease or death. Enrollment for the study began in 2019, and it is anticipated that 9 years of follow-up will be required to observe the required number of primary events. Given the long duration of the study, changes in clinical guidelines were anticipated and have occurred, including the approval of new DKD therapies and introduction of a new formula for estimated glomerular filtration rate (eGFR) calculation. In anticipation of these changes, the study design allows for whatever standard of care is extant at any time during the course of the study. PTXR's pragmatic trial design and protocol leverage the VA's research infrastructure and remote platforms allowing the study to be responsive to external changes and to safely continue during a global pandemic. The CSP 596/OPTION study is a randomized, double- blind, multicenter trial of Veteran patients with a first or second recurrent Clostridium difficile infection (CDI) comparing (1) fidaxomicin and (2) vancomycin, followed by a taper and pulse to (3) a standard vancomycin regimen. Since enrollment began in 2016, significant changes in CDI epidemiology and clinical management have impacted the study. The COVID-19 pandemic also resulted in an administrative hold on all trial activity followed by staggered reopening of sites due to variable COVID-19 activity and clinical priorities. Many clinical laboratories switched to algorithms that included free toxin assays in addition to polymerase chain reaction (PCR) tests out of concern for overdiagnosis based on PCR testing alone, reducing the number of potentially enrollable cases. There has been increased empirical vancomycin treatment for recurrent CDI without confirmation by stool testing, a requirement for enrollment, and a recruitment strategy for identifying potential cases. Finally, conflicting clinical guidelines for recurrent CDI has created potential equipoise when considering enrollment. Ongoing educational efforts have been made to clarify the protocol and emphasize the validity of the research question as well as protoco changes to allow safe enrollment and follow-up of participants in the face of the ongoing COVID-19 pandemic. The CSP 2005/VALOR is a phase III randomized, open label, multicenter clinical trial of Veteran patients with operable stage I non-small cell lung cancer that compares stereotactic radiotherapy and anatomic pulmonary resection with a primary outcome measure of overall survival. The study was activated in 2017 and recruitment to the trial has been affected by ongoing changes in public and clinician perceptions about stereotactic radiotherapy and surgery that have interfered with equipoise and willingness of participants to enroll. The study team perpetually addresses this challenge through group conversations with local site investigators, study coordinators, and other research personnel to preserve group equipoise across the study. Since the study's activation, new safety information about stereotactic radiotherapy has emerged necessitating protocol modifications while aiming to preserve internal and external validity. The includes modifying standard operating procedures for the study's centralized quality assurance program that has had to adapt its process to remain contemporary. STARPORT, funded by VA CSRD with CSP collaboration, is a randomized, open label, multicenter clinical trial of Veteran patients with oligorecurrent prostate cancer comparing the effects of standard systemic therapy (SST) alone or with PET-directed local therapy using surgery or radiation. Although enrollment was initiated in 2021, changes are already evident in clinical practice guidelines regarding the use of imaging in workup in this patient population. Shortly before the start of accrual, 18F-DCFPyL PSMA PET/CT received FDA-approval. Consequently, it is being rapidly adopted at the STARPORT VA medical centers and the use of conventional imaging using CT or bone scan prior to PET/CT imaging-part of the original eligibility criteria-quickly is falling out of favor. Furthermore, shortly after the start of enrollment, NCCN guidelines adopted the stance that conventional imaging was no longer required in the setting of PSMA PET/CT imaging, solidifying the transition away from conventional imaging. Thus, the protocol is being amended to remove the requirement for conventional imaging as part of workup for oligorecurrence. In addition, to be generalizable, the study is designed to integrate future PSMA radiotracers that are incorporated into practice as well as changes in SST regimens over the time of the study.

ACUTE KINDEY INJURY OVER EXISTING CHRONIC KIDNEY DISEASE IN PATIENTS WITH SARS-CoV-2 INFECTION

Introduction: Patients with chronic kidney disease (CKD) and that have SARS-CoV-2 infection are at higher risk of developing acute kidney injury (AKI) and have higher mortality rates after hospital admission. Method(s): The study group included 120 patients: 70 with a history of CKD (eGFR rate of <60 mL/min);and 50 were within the control group with no history of kidney disease. Data on patients' gender, age, co-morbidities, and laboratory results from blood and urine samples, taken at admission into the ER, were collected. Laboratory values included calculated eGFR (by the CKD-EPI 2021 formula), highly sensitive inflammatory markers, D-dimer, blood-cell counts, and changes in urine parameters (hematuria, proteinuria). Co-morbidities included hypertension, obesity, diabetes mellitus, vascular disease, and CKD. All patients had been treated by the official protocol of the Republic of Bulgaria for SARS-CoV-2 treatment, but not all of them have received remdesivir. We also assessed which risk factors may have led to AKI with emphasis to the levels of specific biomarkers (IL-6, IL-18, KIM-1, NGAL, ACE2, SAA). Result(s): Overall median age of patients was 65.7 years;gender ratio was 50% M/F in both groups. Median duration of symptoms before hospitalization was 6 days. Of the 120 patients, 35% were febrile with temperatures >38oC Overall, creatinine level on admission was elevated in 58.3% of cases;eGFR was <60 mL/min/1.73 m2 in 50% of patients. Mean value of eGFR on admission was 82.3 mL/min/1.73 m2 for the non-CKD group and 49.5 mL/min/1.73 m2 for the CKD group. In total, three patients needed renal-replacement therapy: two patients from the CKD group and one from the non-CKD group. Urine samples showed 39 patients had proteinuria: of these, 87.1% had 1+ proteinuria and the others had >1+. Of the 22 cases of hematuria, 54.5% had only 1+ hematuria. Acute kidney injury occurred in 38 patients (31.6%) of whom 31 had CKD (44.3% of CKD patients). Overall, within our cohort of 120 patients, in-hospital mortality was 19.1% (23 patients): of these, 66.6% had AKI (19 patients). Overall, 100% of patients that did not survive Covid-19 also had CKD. We also analyzed risk factors that may have led to AKI. Logistic regression for risk factors for AKI showed that, the factors significantly linked with the incidence of AKI were an eGFR of >=60 mL/min/1.73m2, having symptoms for >=6 or more days before hospitalization, and not having received remdesivir as a treatment. Also, the levels of IL-6, SAA, and KIM-1 were significantly higher for patients that had AKI. Conclusion(s): We found that CKD was not a risk factor for COVID-19-related AKI. Conversely, we found that developing AKI was significantly associated with in-hospitalization death, which was linked with renal inflammatory processes and injury caused by SARS-CoV-2. No conflict of interestCopyright © 2023

Long-Term Evolution of Kidney Function of Covid-19 Survivors Who Were Hospitalized and Did or Did Not Develop Acute Kidney Injury

Introduction: Hospitalized COVID-19 patients are at increased risk for acute kidney injury (AKI, incidence 0.5-80%), which contributes to increased morbidity and mortality. However, the long-term effect of COVID-19 on kidney function is unclear, particularly in populations with a high prevalence of chronic kidney disease like ours. The aim was to assess the evolution, at least 6 months after hospital discharge, of kidney function in COVID-19 survivors who were hospitalized and did or did not develop AKI (KDIGO criteria). Additionally, patient survival was analyzed. Method(s): Prospective cohort of surviving patients with confirmed COVID-19 diagnosis, treated in our hospital from 08/Mar/2020 to 16/Oct/2021. From the inpatient registry, survivors were contacted by telephone;those who agreed to participate had a clinical interview and measurement of biochemical variables, including estimated glomerular filtration rate (eGFR) and albumin/creatinine ratio (ACR) in a single urine sample. Result(s): Of 585 patients hospitalized for COVID-19 and discharged alive, 121 (21%) developed AKI. So far, 166 without AKI and 34 with AKI have been included. Patient evaluations were performed at a mean (+/-SE) of 20.0+/-0.3 months, and main comparisons between groups are shown in Table 1 and Table 2.Overall mean time survival (+/-SE) was 26.1+/-0.5 months, and comparison of survival according to the development of AKI is shown in Figure. [Formula presented] [Formula presented] [Formula presented] Conclusion(s): A fifth part of surviving patients hospitalized for COVID-19 developed AKI, 73% of them recovered kidney function upon discharge. Patients who developed AKI had lower kidney function throughout the study and a higher ACR at the end of follow-up compared to those without AKI;however, this latter group displayed a slight decrease in eGFR at the end of the study compared to its baseline value. Survival of patients was significantly lower in those with AKI, and it was worse in those with higher stages. No conflict of interestCopyright © 2023

Family History of Alport Syndrome with Spectrum of Chronic Kidney Disease, Dialysis and Transplantation

Introduction: Alport syndrome should be considered in the differential diagnosis of patients with persistent microhematuria. Electron microscopic examination of renal tissue remains the most widely available and applied means for diagnosing AS. The presence of diffuse thickening and multilamellation of the GBM predicts a progressive nephropathy, regardless of family history. Unfortunately, ultrastructural information alone does not establish the mode of transmission in a particular family. Method(s): 18 years-old male patient was followed in the clinic due to persistent microscopic haematuria and proteinuria. Family history is significant for one brother in his early 20s, who started to have the presentation early in life and his initial biopsy showed thin basement membrane disease. The brother subsequently progressed to renal failure and a repeat biopsy confirmed the presence of Alport syndrome. Another brother had end-stage renal disease and underwent renal transplantation. The patient status was revised, and genetic studies confirmed the presence of an autosomal recessive type of Alport syndrome involving collagen for A3 chain COL4A3. His kidney function remained stable initially with an estimated GFR of approximately 90 mL/min/1.73 m2. The most recent eGFR is around 70 ml/min/1.73 m2. His proteinuria disappeared once Losartan 25 mg was added to Ramipril 5 mg. His blood pressure has been on target. Creatinine increased to 147 micromol/L and he was diagnosed as having acute kidney injury on chronic renal disease which was obvious post covid infection, then back to baseline. Current proteinuria 3 g/g Cr on Angiotensin receptor blockers. BP 110/70, all other systemic examination is unremarkable. No hearing or visual abnormalities. Result(s): The initial renal manifestations in early childhood include asymptomatic-persistent microscopic hematuria and rarely gross hematuria. At the onset, the serum creatinine and blood pressure are normal. Over time, proteinuria, hypertension, and progressive renal insufficiency develop. ESRD usually occurs between the ages of 16 and 35 years and rarely can occur between 45 and 60 years. Renal biopsy findings of thinning and multilaminar splitting of the glomerular capillary basement membrane seen on electron microscopic examination are pathognomonic. In 2013, an expert panel issued guidelines recommending genetic testing as the gold standard for the diagnosis of Alport syndrome. Currently, a skin biopsy using commercially available monoclonal antibody against the type IV collagen alpha-5 chain (COL4A5). If the protein is clearly absent in a suspected male, a diagnosis of Alport syndrome can be made without further testing. Conclusion(s): Males with X-linked AS due to a deletion mutation of the alpha 5 chain of type IV collagen usually progress to ESRD by the second or third decade of life. Likewise, patients with autosomal recessive AS due to mutations affecting alpha 3 or 4 chains of type IV collagen tend to progress to ESRD by age 30. Autosomal-dominant AS with heterozygous mutations of COL4A3 or COL4A4 usually has a slower progression of CKD. Treatment is blood pressure control with RAAS inhibitors where clinically appropriate. Cyclosporine may be helpful in some patients with stage I and II CKD with significant proteinuria. Caution using calcineurin inhibitors is indicated in all patients with more advanced CKD stages due to potential nephrotoxicity. No conflict of interestCopyright © 2023

High Seroconversion Rates after 2 Doses of Vaccine against Sars-Cov-2 in Kidney Transplant Recipients

Introduction: Immunoglobulin (Ig)G antibodies against SARS-CoV-2 are implicated in herd immunity. Humoral response to vaccines in kidney transplant recipients (KTRs) is documented to be sub-optimal. However, the response to non-messenger RNA(mRNA) based vaccines in KTRs is not known Methods: SARS-CoV-2 spike protein IgG antibody response was assessed in KTRs using chemiluminescence immunoassay. Patients were characterized by the number of vaccine doses received and Coronavirus disease 2019 (COVID-19) infection in past. Result(s): Out of 224 KTRs evaluated, 197 (87.94%) had positive S1/S2 IgG anti-SARS-CoV-2 antibodies with a median [IQR] titre of 307.5 AU/ml [91 AU/ml - 400 AU/ml]. High titres (in neutralizing range) were found in 170/224 (75.9%) KTRs. Seropositivity rates after 2 doses of vaccination were significantly higher than unvaccinated KTRs (88.67% vs 66.7%;p = 0.006). After adjusting for cofounders, KTRs with diabetes at the time of vaccination were less likely to develop antibody response (aOR 0.31, 95% confidence interval [CI] - 0.10, 0.90;p = 0.032). Higher eGFR was also an independent predictor of antibody response (aOR 1.04 95% CI - 1.01, 1.08;p = 0.005). KTRs vaccinated with CovishieldTM developed higher antibody response as compared to CovaxinTM (aOR 5.04, 95% CI - 1.56, 16.22;p = 0.007). Conclusion(s): A high rate of seroconversion was seen in KTRs after SARS-CoV-2 vaccination with non mRNA vaccines. The presence of diabetes and decreased eGFR independently predicted lower seroconversion rates. No conflict of interestCopyright © 2023

Using Telemedicine Compared with Face-to-Face Visits for Outpatient Management in Chronic Kidney Disease Patients: A Non - Randomized Open Label Controlled Trial

Introduction: In the recent past, Coronavirus disease 2019 (COVID-19) was a pandemic, and it has had a profound impact on health. Especially patients with kidney disease are at increased risk for morbidity and mortality from COVID-19. Telemedicine is thought to be used for outpatient management in chronic kidney disease (CKD) patients because we want to reduce hospital visits and congestion in CKD clinic to decrease the risk of COVID-19 infection in CKD patients. In addition, CKD patients can receive care continuously during the COVID-19 pandemic. This study aimed to compare the effectiveness of telemedicine with face-to-face visits in CKD patients' care. Method(s): A single-center, non-inferiority, non - randomized open-label controlled trial in a CKD clinic, A total of 64 CKD patients (eGFR < 60 ml/min/1.73 m2) were recruited in this study. The patients were divided into 2 groups, using telemedicine and face-to-face visits, voluntarily by the patients. The study was followed for a period of 6 months. To compare the percentages change of estimated glomerular filtration rate (eGFR-EPI) between 2 groups was the primary outcome. Secondary outcomes were comparing all-cause mortality, hospitalization, emergency department visits, rate of renal replacement therapy initiation, comorbidity and CKD complication, adherence in follow-up, timing in visit, travel cost, and satisfaction with the service. Result(s): There were 32 patients in both telemedicine and face-to-face visit arms. The majority were male (60.9%). The mean age was 72.2 +/- 11.2 (SD) years. CKD KDIGO stage 4 was the majority (56.2%) and mean eGFR-EPI was 24.6 +/- 9.9 (SD) ml/min/1.73 m2. Most of the co-morbidities were hypertension (96.9%), diabetes mellites (73.4%), and dyslipidemia (64.1%). The eGFR was increased from the baseline of 2.2% in the telemedicine group and decreased by 6.1% in the face-to-face visits group (p = 0.119). There was no difference between the 2 groups in all-cause mortality, hospitalization, emergency department visits, rate of renal replacement therapy initiation, comorbidity and CKD complication controlled, adherence in follow-up, and satisfaction with the service. Quality of life in the telemedicine groups was higher than in the face-to-face visits group (69.5 vs 58.4 scores, p = 0.009). The telemedicine group was shorter timing in visit than the face-to-face visits group (52.5 vs 189.5 minutes, p < 0.001). Conclusion(s): Telemedicine for outpatient management in CKD patients is not inferior in the percentage change of eGFR, comorbidity and CKD complication controlled compared with face-to-face visits. Telemedicine tends to have a better quality of life, shorten the timing of the visit, and lower travel costs to the hospital. No conflict of interestCopyright © 2023