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Calcium levels in the Coronary Artery are an indicative marker of the presence and extent of atherosclerosis. This serves as an additional prognostic indicator in addition to traditional risk factors. Moreover, the coronary calcium test is associated with a descriptor known as the calcium score or calcium score (Cs), which is primarily useful for stratifying the risk of asymptomatic patients, while for patients with acute or chronic chest pain, coronary axial computed tomography is generally required. A retrospective analysis of data was conducted in the radiology department of King Salman Specialist Hospital in Hail City, the kingdom of Saudi Arabia, between January and May 2022. A total of 40 patients were randomly selected, 25 males and 15 females. The study included all patients with or suspected of having a calcium deposit who underwent a CT scan using the Siemens SOMATOM definition MDC scan. Patients underwent a scan with the preparations and laboratory tests required for their coronary artery calcium scores. In this study, males were more likely to be affected by calcium deposits (64%), whereas females were 36%. Approximately 50 percent of the study populations were found to be normal (no identifiable calcium deposits) and 37.5% to have moderate calcium deposits. There is a significant association between CACS and moderate CVD risks based on age and gender in this study. Better control of cardiovascular system (CVS) risks is recommended in all primary care centers in the Kingdom of Saudi Arabia (KSA).Copyright © 2022 International Journal of Pharmaceutical Research and Allied Sciences. All rights reserved.
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ABSTRACT Objective: To determine the effect of Remdesivir on liver enzymes and renal functions in SARS-CoV-2 patients. Methods: This prospective cohort study was conducted at Dr. Ruth KM Pfau, Civil Hospital Karachi between 1st December 2021 to 31st January, 2022. All patients of severe SARS-CoV-2 infection who received Inj. Remdesivir for five days as per protocol of SARS-CoV-2 management were included. Biodata of selected patients including age, gender, diabetic, hypertensive status was recorded. Patients Liver Function Tests and Serum Creatinine were performed on days 0, 3, 5, 7 and 14. Results: This study included 85 patients, out of which 55 (64.7%) were males and 30 (35.3%) were females. Out of 85 patients, Remdesivir was stopped in 3 (3.5%) patients. Among these three patients Remdesivir was stopped in one patient on day three because of decrease in CrCl to <30 ml/min. His CrCl improved after stopping Remdesivir. In the remaining two patients, Remdesivir was stopped due to increase in ALT to greater than 10 times from normal values on day three. Similarly, in these two patients the ALT improved after stopping Remdesivir. Conclusion: Only three patients developed adverse effects resulting in stopping of Remdesivir, however these were reversible on stopping the drug. Therefore, Remdesivir is a relatively safe drug and well tolerated in SARS-CoV-2 patients.
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Background: The approval of atezolizumab + bevacizumab for untreated advanced HCC was a significant benefit for patients, but with an increased risk of potentially severe bleeding complications. Tivozanib (a selective VEGFR 1, 2, & 3 tyrosine kinase inhibitor [TKI]) has been combined with durvalumab in the DEDUCTIVE study;preliminary results presented in January 2022 showed that this combination was well tolerated with comparable efficacy to other immune checkpoint and VEGF containing regimens in patients with previously untreated HCC (J Clin Oncol 40, no. 4 suppl 462-462). We now report the final results of this cohort (cohort A) of patients as well as those with previously treated HCC, including safety results for all the patients. Method(s): Major eligibility criteria included age .18 yrs with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, and creatinine clearance .40 ml/min. Major exclusion criteria included co-infection with HBV and HCV and significant organ dysfunction. Patients were treated with 0.89 mg tivozanib p.o., 21 days on followed by 7 days off and 1500 mg durvalumab i.v. every 28 days. The primary objective was to determine the safety and tolerability of this combination in patients with advanced HCC;secondary objectives included assessing objective response rate (ORR), progression free survival, and overall survival (OS). The study was amended in 2021 to include a cohort of patients previously treated with atezolizumab and bevacizumab (cohort B). Result(s): 21 patients were enrolled in cohort A and 6 in cohort B;the median age was 67, 88% of patients were male, and 24% were Asian. The median followup time was 13.2 mos and 3.4 mos for cohorts A and B, respectively. Data were available for 25 of the 27 patients enrolled. For cohort A, the ORR was 25% (5/20) and 1-year OS was 76%. For safety analysis, 24 (96%) patients had at least 1 treatment-emergent adverse event (TEAE);92% were attributed possibly to either tivozanib or durvalumab;32% were serious TEAEs and there was 1 TEAE leading to death (unrelated). Of the 8 (32%) serious TEAE, 2 were coronavirus infection. 2 patients had serious (grade 3) treatment-related AEs: 1 pneumonitis and 1 with gastrointestinal hemorrhage and anemia. There were no grade 4 or 5 treatment-related AEs. Conclusion(s): Treatment with the combination of tivozanib and durvalumab in patients with either untreated advanced HCC or those previously treated with atezolizumab and bevacizumab was well tolerated;no severe bleeding events occurred in this study. Efficacy outcomes were comparable to other IO-TKI combinations in HCC. Data for PDL1 status, HBV/HCV status was collected and will be presented along with final safety and efficacy results for both cohorts.
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Aim: The aim of the study was to evaluate the management and outcomes of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a secondary hospital. Material(s) and Method(s): This study included 699 hospitalized patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 on chest computed tomography (CT). Demographics, comorbidities, initial laboratory tests on admission, treatment modalities, complications and outcomes were evaluated retrospectively. Result(s): The mean age was 57.0+/-15.6 (range:16-94 years), and male to female ratio was 1.24;58.7% of the patients had at least one underlying comorbidity, the most common was hypertension;18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3% had increased lactate dehydrogenase, and 58.5% had increased D-dimer. Chest CT revealed moderate and severe stages in 57.9% of the patients. Hydroxychloroquine was given to 37.2% and favipiravir to 67.1% of the patients. No significant difference was observed between treatment groups in terms of mortality (P=0.487);5.8% of the patients were transferred to the ICU, 75.6% of whom needed non-invasive and 36.5% invasive mechanical ventilation. The overall case-fatality rate was 0.9. Discussion(s): Older age, male gender, low lymphocyte count, CT findings, including bilateral involvement and severe stage were significantly associated with poor prognosis and mortality.Copyright © 2022, Derman Medical Publishing. All rights reserved.
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Background Cardiac rehabilitation (CR) has shown clinical benefit in heart transplant (HT) recipients. However, variable adherence with CR has been reported. We aimed to describe adherence and factors associated with CR cessation. Methods We performed a retrospective chart review of HT recipients who attended at least one CR session at a tertiary medical center (2013-2021). Complete adherence was defined as participation in all 36 CR sessions. We extracted participant age, sex, race, BMI, diabetes, creatinine clearance, post-operative complications (reoperation, major bleeding, infection, or need for dialysis), hospital length of stay, and METs on baseline exercise tolerance test prior to CR. We computed the proportion of HT recipients who did not complete CR, and then compared their characteristics to those of HT recipients with complete adherence using Kruskal Wallis tests and Fisher's Exact tests for continuous and categorical variables, respectively. Primary reasons for cessation were extracted from the electronic health record. Results There were 55 HT recipients (median age 55.9 years, 67.3% male) who attended CR;25 (45.5%) had complete adherence. Thirty did not complete CR (14 patients attended 1-12 sessions, 12 patients attended 13-24 sessions, and 4 patients attended 25-35 sessions) and participated in a median of 13 sessions (IQR 9-21). Within this group, 46.7% reported medical reasons for cessation, 20.0% for personal reasons, 13.3% for COVID-19 pandemic, 6.7% for insurance expense, 3.3% for relocation, and 3.3% for return to work or school. Patients who did not complete CR experienced more post-operative complications after HT (63.3% vs 32.0%, p = 0.03) but there were no other differences in characteristics between groups. Conclusion Nearly half of HT recipients in our sample had complete adherence to CR. Among those who did not complete CR, medical reasons were most commonly cited. Postoperative complications predicted CR cessation, but there were no other differences between groups, albeit with a relatively small sample size.Copyright © 2023 American College of Cardiology Foundation
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Objective: To determine the effect of Remdesivir on liver enzymes and renal functions in SARS-CoV-2 patients. Methods: This prospective cohort study was conducted at Dr. Ruth KM Pfau, Civil Hospital Karachi between 1st December 2021 to 31st January, 2022. All patients of severe SARS-CoV-2 infection who received Inj. Remdesivir for five days as per protocol of SARS-CoV-2 management were included. Biodata of selected patients including age, gender, diabetic, hypertensive status was recorded. Patients Liver Function Tests and Serum Creatinine were performed on days 0, 3, 5, 7 and 14. Result: This study included 85 patients, out of which 55 (64.7%) were males and 30 (35.3%) were females. Out of 85 patients, Remdesivir was stopped in 3 (3.5%) patients. Among these three patients Remdesivir was stopped in one patient on day three because of decrease in CrCl to <30 ml/min. His CrCl improved after stopping Remdesivir. In the remaining two patients, Remdesivir was stopped due to increase in ALT to greater than 10 times from normal values on day three. Similarly, in these two patients the ALT improved after stopping Remdesivir. Conclusion: Only three patients developed adverse effects resulting in stopping of Remdesivir, however these were reversible on stopping the drug. Therefore, Remdesivir is a relatively safe drug and well tolerated in SARS-CoV-2 patients.
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INTRODUCTION: While COVID19 was initially thought to only affect the lungs, the virus also affects other organs including the kidneys. This has led to reports of renal function alterations including impairment and enhancement. The incidence of acute kidney injury (AKI) and augmented renal clearance (ARC) has been reported to be 25-35% and 25-75%, respectively. Several risk factors for AKI and ARC have been reported with many overlapping. This study sought to identify which patients might experience AKI vs ARC. METHOD(S): Hospitalized, adult patients with laboratory confirmed COVID19 from the National COVID Cohort Collaborative (N3C) database were included in this retrospective study. Patients who had all data to calculate creatinine clearance (CrCl) via Cockroft-Gault were screened and excluded for pregnancy, body mass index < 18kg/m2, history of end-stage renal disease on dialysis or nephrectomy, or lacking data to determine exclusion criteria. AKI and ARC were defined using AKIN criteria and CrCl >130mL/min, respectively. Potential demographic and biomarker predictors of AKI or ARC were considered in univariate and multivariate logistic regression models. RESULT(S): 11,274 patients were included in univariate and multivariate logistic regression analysis. 20.1% developed AKI and 34.2% experienced ARC. Significant variables associated with AKI included age, weight, height, white race, male sex, Hispanic ethnicity, and diabetes (OR 0.996, 1.01, 0.73, 0.969, 1.1, 1.11, and 1.06, respectively). Age, weight, black race, male sex, Hispanic ethnicity, and hypertension were all associated with experiencing ARC (OR 0.973 1.01, 0.753, 0.945, 1.15, 0.911, respectively). No biomarker variables were available from N3C database. CONCLUSION(S): While a significant proportion of patients with COVID19 experience alterations in renal function, there are many overlapping risk factors for the development of AKI or ARC including age, weight, and Hispanic ethnicity, with male sex as the only differentiating patients at risk for AKI vs ARC. Thus, determining which patient may be at risk for renal dysfunction or enhancement based on their demographic is still unknown. Further investigation is needed to identify patients who are at risk for each of these renal function alterations.
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Background: The four-drug combo has becoming one of the main induction treatment for TE NDMM patients (pts). We conducted a phase 2 study to assess the safety and preliminary efficacy of Cyclophosphamide (C), thalidomide (T), dexamethasone (d)-(CTd) and Dara combination. MAXDARA study has shown in the primary analysis with 21 included patients (pts), 4 and 8 pts MRD negativity after four induction cycles and two consolidation cycles post transplant, respectively. (Crusoe E et al ASH 2020, 2416 poster presentation). In the present analysis we evaluate the effect of deep response rate on PFS. Method(s): This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the ECOG performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. The MRD was evaluated by next-generation flow (NGF) 10-6 and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method and PFS analysis were performed based on the different response rates. (Data cut-off was April 2022) Results: A total of 24 pts were included. The median age being 58 (range 37- 67 years), 15 (62.5%) pts were female, 22 (92%) were non-white, 6 (25%) had an R-ISS = 1, 12 (50%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Sixteen (66.7%) pts were IgG isotype and Six (25%) had high-risk chromosomal abnormalities [1q+, del17p, t(4;14) or t(14;16)]. To date, 23 pts have completed induction, 21 performed transplant and 14 are still in treatment after one year of dara maintenance. By ITT analysis, 22 pts (91.6%) achieved (> PR) after 4 induction cycles. One pts achieved SD, one MR and one sCR. Eleven (39%) pts achieved PR, and 10 (35.7%) VGPR. After two consolidation cycles, ORR was 68%, 8 (28.6%) and 11 (39.3%) pts obtained sCR and VGPR, respectively. The best response during any time of the treatment were PR in 3 (12.5%) pts, VGPR in 12 pts (50%) and sCR in 8 (33.3%) pts. In a ITT analysis, NGF MRD 10-6 negativity were observed in 4(16.6%) after four induction cycles, and in 17 (70.8%) pts after two consolidation cycles post-ASCT. In a ITT analysis, after a median follow up (FU) of 26 months, the PFS was 37months for the entire group. The median PFS comparing sCR vs < VGPR were 37m vs 27m (p = 0.021), respectively, and comparing MRD negative by NGF vs no, had impacted even more on PFS with a median of 37m vs 16m (p = 0.004), respectively. The OS was not yet achieved and 83% of the patients still alive after a median FU of 27m. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Summary/Conclusion: The Daratumumab - CTd protocol is an active and safe regimen capable of producing deep and sustainable responses. The deeper response rate impacted on PFS, confirm that MRD negativity is critical to patient outcome. Copyright © 2022
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Introduction: COVID19 was originally thought to be solely a respiratory disease, however, other organs, such as the kidneys, are often also affected. While acute kidney injury (AKI) and augmented renal clearance (ARC) have both been documented, the incidence, renal characteristics, and outcome of each derangement have not been fully elucidated. Research Question or Hypothesis: What are the incidences, characteristics, and outcomes of AKI, ARC, and no AKI/ARC in patients hospitalized with COVID19? Study Design: Retrospective, observational cohort study Methods: Inpatient data from the National COVID Cohort Collaborative database with laboratory confirmed COVID19 who were >18 years old were utilized. Patients who had all data to calculate creatinine clearance (CrCl) via Cockcroft-Gault equation were screened. Exclusion criteria were pregnancy, body mass index <18kg/m2, history of end-stage renal disease on dialysis or nephrectomy. Episodes of AKI and ARC were defined using AKIN criteria and CrCl >130mL/min, respectively. Renal function characteristics and outcomes included days with episode, hospital length of stay (LOS), and mortality. Descriptive statistics and Mann-Whitney U tests were used for statistical analysis where appropriate with p<0.05 indicating statistical significance. Result(s): 15,608 patients from 11 sites were included. Overall, 57.3% were male with median age 62.7[50.1-73.2] years. The incidence of No AKI/ARC, AKI, and ARC was 43.5%, 22.9%, and 33.6%, respectively. Episodes of ARC lasted longer than AKI (4[2-7] vs 3[1-6] days;p<0.0001) Patients with AKI and ARC both had longer LOS compared to no AKI/ARC (19[10-34] and 6[4-11] vs 6[4-10];p<0.001). Patients with AKI had the highest mortality followed by no AKI/ARC then ARC (41.7% vs 10.1% vs 5.4%;p<0.001). Conclusion(s): A significant proportion of patients with COVID19 exhibit altered renal function throughout hospitalization. Clinicians should be mindful of these alterations given their associations with increased LOS and mortality with AKI. Future research should explore the impact of ARC on medication therapy in patients with COVID19.
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Background: Obesity, which is becoming increasingly common worldwide, is known to be associated with cardiovascular disease and progression of chronic kidney disease, due to inappropriate activation of the renin-angiotensin system. Many angiotensin II effects are dependent on AT1 stimulation of reactive oxygen species (ROS). In COVID-19 patients, overweight and obesity are associated with acute respiratory distress syndrome and AKI. Although obesity increases oxidative stress, endothelial dysfunction and inflammation, its effect on IRI-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. Method(s): We fed mice a high-fat or standard diet (45 and 10 kcal% fat, respectively) for 8 weeks. Some then underwent bilateral 30-min clamping of the kidney hila and subsequent reperfusion (groups: obese, normal, obese+IRI and normal+IRI). All studies were performed 48 h after IRI. Data are mean+/-SEM. Result(s): Body weight (g) was 33+/-1.7, 32+/-0.7, 27+/-1.4 and 26+/-0.9 in the obese, obese+IRI, normal and normal+IRI groups, respectively (P<0.001). Mortality was 42% and 25% in the obese+IRI and normal+IRI groups, respectively (P <0.05);there were no deaths in the non-IRI groups. Serum glucose and cholesterol did not differ among the groups. Creatinine clearance (mL/min/100g BW) was 0.20+/-0.05 and 0.20+/-0.07 in the obese+IRI and normal+IRI groups, respectively, vs. 0.34+/-0.06 and 0.40+/-0.08 in the obese and normal groups, respectively. Renal p65 protein expression (%) was 127+/-4.8 in the obese+IRI group, vs. 100+/-4.1, 92.5+/-4.8 and 107+/-3.7, respectively, in the normal, obese and normal+IRI groups (P<0.05). Conclusion(s): In obese individuals with AKI, ROS could be a therapeutic target (FAPESP, NWO).
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Purpose: Lung transplant is the last resort for COVID-19 refractory ARDS. Dual organ transplant is seen as a relative contraindication at many institutions. We describe a case of simultaneous Lung-Kidney transplant (SLK) in a patient with COVID-19 ARDS. Method(s): A 24-year-old patient with no PMH presented to an outside hospital with a week of shortness of breath, cough, and fever. Despite treatment with Remdesivir and dexamethasone, the patient developed hypoxemic respiratory failure with acute renal injury requiring ICU care and intubation, V-V ECMO, and dialysis. Additionally, Intravenous and inhaled Aviptadil were given under emergency use authorization. While oxygenation improved, the patient could not be weaned off ECMO. With a LAS score of 90.29, the patient underwent an SLK transplant on HD 53, requiring standard induction and maintenance immunosuppression therapy. The patient was treated post-operatively for PGD as well as for subclinical AMR. After successful inpatient rehabilitation, the patient was discharged home after four months and had a one-month follow-up on room air and normal creatinine clearance. Result(s): Patients with pre-existing renal dysfunction who have undergone lung transplants have a significantly higher one- and three-year mortality than patients with normal GFR. The patient's survival after SLK was similar to isolated lung transplants at one and five years, according to an analysis of the UNOS/OPTN database. Still, dual organ transplant in the COVID-19 ARDS population is considered a contraindication at many centers, given these patients' critical illness and frailty. However, the frailty in this population is reversible due to the rapid onset of disease in an otherwise previously healthy younger population with minimal comorbidities. Thus, multiorgan transplantation should be considered in such a patient population. Our patient received Aviptadil as part of an EIND to stabilize patients and improve oxygenation while waiting on the transplant list. Conclusion(s): We propose that SLK transplantation should be considered for carefully selected patients with COVID-19 ARDS.
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SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Magnesium citrate is an osmotic laxative which is occasionally used in the intensive care unit (ICU) for refractory constipation. We present a patient in whom a bowel regimen containing magnesium citrate resulted in severe hypermagnesemia with paralytic ileus, requiring renal replacement therapy. CASE PRESENTATION: 70-year-old male was admitted to the ICU for COVID-19 associated acute hypoxic respiratory failure and suffered multi-day, refractory constipation, treated with one dose of 17 grams of magnesium citrate. Vital signs were remarkable for bradycardia and hypotension. On examination, patient was lethargic and the abdomen was soft and non-distended, but there were decreased bowel sounds throughout. Subsequently, laboratory findings were notable for a magnesium level of 8.8 mg/dL and serum creatinine of 2.3 mg/dL (estimated glomerular filtration rate 28mL/min/1.73m2), all of which were previously normal at admission. Computerized Tomography of the abdomen was performed showing dilated cecum, ascending and transverse colon and moderate to large amount of intraluminal rectal stool and air. Patient was started on intravenous fluids, loop diuretics, and calcium gluconate, however, the patient required renal replacement therapy for magnesium clearance. Patient clinically improved with normalization of kidney function and magnesium levels as well as resolution of ileus. DISCUSSION: Magnesium homeostasis is regulated by gastrointestinal absorption and renal excretion, for which the kidney maintains magnesium equilibrium until creatinine clearance falls below 20 ml/min [1]. Elevated magnesium levels can decrease bowel motility by blocking myenteric neurons and interfere with excitation - contraction coupling of smooth muscle cells as well as serve as a reservoir for continuous magnesium absorption [2]. Our patient suffered acute kidney injury, likely from COVID-19 pneumonia and acute tubular necrosis from shock, placing him at increased risk for hypermagnesemia. One retrospective study identified that patients with COVID-19 are more prone to the development of hypermagnesemia, which is associated with renal failure and increased risk of mortality [3]. The magnesium load from magnesium citrate in our patient created for a seemingly out of proportion effect of hypermagnesemia-induced paralytic ileus and presumably a magnesium reservoir, refractory to conservative measures. CONCLUSIONS: The use of magnesium containing bowel regimens should be considered with caution due to the possibility of hypermagnesemia in at-risk patients, which may result in paralytic ileus and other sequelae. Hypermagnesemia reduces colonic peristalsis and interferes with magnesium equilibrium, prolonging its effects. There are rare case reports in the literature discussing this phenomenon, but should be further evaluated for specific patient susceptibility and effects on morbidity and mortality. Reference #1: Cascella, M. (2022, February 5). Hypermagnesemia. StatPearls [Internet]. Retrieved March 16, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK549811/ Reference #2: Bokhari, S., Siriki, R., Teran, F., & Batuman, V. (2018, September 8). Fatal Hypermagnesemia due to laxative use. The American Journal of the Medical Sciences. Retrieved March 16, 2022, from https://www.amjmedsci.org/article/S0002-9629(17)30467-6/fulltext Reference #3: Stevens, J. S., Moses, A. A., Nickolas, T. L., Husain, S. A., & Mohan, S. (2021, July 29). Increased mortality associated with hypermagnesemia in severe covid-19 illness. American Society of Nephrology. Retrieved March 16, 2022, from https://kidney360.asnjournals.org/content/2/7/1087 DISCLOSURES: No relevant relationships by Adnan Abbasi No relevant relationships by Sarah Upson
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BACKGROUND: Because the consequences of the lifestyle changes in older adults associated with the social isolation imposed in response to the COVID-19 pandemic are not fully understood, here, we investigated the effects of one year of social isolation imposed by COVID-19 on the metabolic parameters and functional physical capacity of older women who regularly practiced physical exercises before the pandemic. METHODS: Systemic lipid and protein profiles, estimated creatinine clearance (ECC), and functional physical capacity (FPC) were assessed before (January-February 2020) and 12 months after social isolation in 30 older women (mean age 73.77 ± 6.22) who were engaged in a combined-exercise training program for at least 3 years before the COVID-19 pandemic. RESULTS: In this group, we observed increased plasma levels of triglycerides and creatinine, an increase in the time necessary to perform gait speed and time-up-and-go tests, and reduced muscle strength assessed by the handgrip test and ECC post-COVID-19 pandemic relative to values recorded pre-pandemic. In addition, we observed significant correlations (both negative and positive) between anthropometric, some metabolic parameters, and physical tests. CONCLUSION: One year of interruption of physical exercise practice imposed in response to the COVID-19 pandemic significantly altered some systemic metabolic parameters and worsened ECC and FPC in older women.
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Background: Patients with relapsed or refractory (R/R) LBCL after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) hae poor outcomes and limited treatment options. Aims: PILOT (NCT03483103) ealuated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as second-line treatment in patients with R/R LBCL not intended for HSCT. Methods: Eligible patients were adults with R/R LBCL after first-line treatment who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria as follows: age ≥ 70 years, Eastern Cooperatie Oncology Group performance status (ECOG PS) of 2, diffusing capacity for carbon monoxide ≤ 60%, left entricular ejection fraction < 50%, creatinine clearance < 60 mL/min, or alanine aminotransferase/aspartate aminotransferase > 2 × the upper limit of normal. Bridging therapy was allowed. Patients receied lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by liso-cel infusion at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Neurological eents (NE) were defined as inestigator-identified neurological aderse eents related to liso-cel and graded using the National Cancer Institute Common Terminology Criteria for Aderse Eents, ersion 4.03. The primary endpoint was objectie response rate (ORR) per independent reiew committee;all patients had ≥ 6 months of follow-up from first response. Results: Of 74 patients who underwent leukapheresis, 61 receied liso-cel and 1 receied nonconforming product (ie, product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered lisocel). Common reasons for preinfusion dropout included death and loss of eligibility (5 each). For liso-cel-treated patients, median age was 74 years (range, 53-84;79% ≥ 70 years) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectiely;26% had ECOG PS of 2 and 44% had Hematopoietic Cell Transplantation-specific Comorbidity Index score ≥ 3. After first-line treatment, 54% were chemotherapy refractory, 21% relapsed within 12 months, and 25% relapsed after 12 months;51% of patients receied bridging chemotherapy. Median (range) onstudy follow-up was 12.3 months (1.2-26.5). ORR and complete response rate were 80% and 54%, respectiely (Table). Median duration of response and progression-free surial were 12.1 months and 9.0 months, respectiely. Median oerall surial has not been reached. The most frequent treatment-emergent aderse eents (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade 3 CRS in 1 patient (2%) and no grade 4/5 CRS eents. Any-grade NEs were seen in 31% (n = 19) of patients;grade 3 NEs occurred in 5% (n = 3) of patients and no grade 4/5 NEs were reported. Seen percent (n = 4) receied tocilizumab only, 3% (n = 2) receied corticosteroids only, and 20% (n = 12) receied both tocilizumab and corticosteroids for treatment of CRS and/or NEs. Oerall, grade ≥ 3 TEAEs occurred in 79% (n = 48) of patients, with grade 5 TEAEs in 2 patients (both due to COVID-19). Two patients (3%) had grade 3/4 infections and 15 (25%) had grade ≥3 neutropenia at Day 29. Summary/Conclusion: In the PILOT study, liso-cel as second-line treatment in patients with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable oerall and complete responses, with no new safety concerns. (Table Presented).
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Background: Acute kidney injury (AKI) is one of the most common complications associated with mortality. Aim: This study aims to find the correlation between renal dysfunction and inflammatory markers and their outcome in COVID-19 patients. Methods: The study was carried out in 100 patients whose inflammatory markers were available on the day of admission among the 814 patients with COVID-19. Results: Fifty-six percent of patients had moderate, and 36% of patients had severe disease outcomes including mortality in nine patients. Out of all the factors studied, advanced age, presence of chronic liver disease, increased levels of blood urea, serum creatinine and lactate dehydrogenase (LDH), decreased creatinine clearance were found to be significantly associated with risk of mortality (P < 0.05). Out of all the factors studied, advanced age increased interleukin (IL)-6 values, increased serum ferritin values, and known cases of hypertension (HTN) were found to be significantly associated with the occurrence of AKI (P < 0.05). The death rate among those with AKI was more than double, i.e., 13.3% compared to only 5.5% without AKI. It was found that only IL-6 was significantly more in those who died having AKI compared to those who recovered with AKI (P < 0.05) but other inflammatory markers were not significantly associated with this (P > 0.05). Conclusion: Significant risk factors of AKI were advanced age, increased IL-6 values, increased serum ferritin values, and known cases of HTN. Significant risk factors for mortality were advanced age, presence of chronic liver disease, increased levels of blood urea, serum creatinine and LDH, decreased creatinine clearance.
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Background: Remdesivir (RDV), a potent nucleotide inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, effectively reduces COVID-19 related hospitalization in outpatients at high risk for progression to severe disease. However, limited data exist on the safety profile of RDV in this population. Methods: We conducted a Phase III placebo-controlled study evaluating a 3-day regimen of RDV in non-hospitalized patients who are at risk for disease progression (age>60 years or underlying comorbid condition). Patients were randomly assigned 1:1 to receive intravenous RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo (PBO). The primary safety endpoint was the proportion of patients with treatment-emergent adverse events (AEs). AEs were evaluated through day 28 and lab abnormalities were evaluated through day 14. Results: 562 patients were randomized and initiated treatment (279, RDV;283, placebo). Baseline characteristics were balanced between groups. Thirty percent were ≥60 years old and most common comorbidities were diabetes mellitus (62%), obesity (56%;median BMI, 30.7 kg/m2), and hypertension (48%). RDV was well tolerated with a similar rate of any AEs between groups (Table). Patients treated with RDV had fewer Grade ≥3 and serious AEs (SAEs) compared to PBO, but had more study-drug related AEs, with the most common one being nausea (18 [6.5%] in RDV vs. 10 [3.5%] in PBO). Grade 3 or higher ALT elevation was reported in 1 (0.4%) RDV vs. 2 (0.7%) PBO treated patients. Median change from baseline in AST, ALT, and bilirubin was similar between groups (Table). Grade 3 or higher decrease in creatinine clearance (CrCl) occurred more often in RDV vs. to PBO treated patients (5.6% vs 1.9% respectively). Most decreases in creatinine clearance occurred within the normal serum creatinine range, occurred after completion of RDV therapy, and resolved on follow-up. Median changes in CrCl from baseline were similar between groups and no renal AEs were reported (Table). Incidence of cardiac-related AEs was similar between RDV and PBO groups. All bradycardia events occurred in the PBO group. No patient experienced a serious AE or drug discontinuation due to hypersensitivity. Conclusion: Treatment with RDV was safe and well tolerated in non-hospitalized patients with risk factors for COVID-19 disease progression. Patients in the RDV group had similar type, incidence, and severity of AEs and lab abnormalities as those receiving PBO.
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Background: Some in vitro, animal, and epidemiological data suggest that tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) might be an efficacious treatment for COVID-19 Methods: In a multicenter open-label, pragmatic, randomized trial in 25 hospitals in Spain we included participants with symptomatic SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance > 60 mL/min, > 60 years or younger if they had at least 2 comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were randomized to receive or not TDF/FTC. Randomization was stratified by age group, symptoms duration (< or ≥ 5 days) and health care setting (hospitalized, long-term care facility, ambulatory). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increased O2 requirements, need for mechanical ventilation or increase in medical therapy: steroid dose, need for tocilizumab). At any moment during the trial participants with room air O2 saturation < 95% and ≥ 1 increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB) Results: 355 participants included (TDF/FTC n=177, no TDF/FTC n=178), median age 67 years (IQR 62-73), male (64.5%), median days of symptoms 8 (IQR 5-10), 29% with < 5 days of symptoms, 96.9% hospitalized, 35.5% with 1 and 36.6 % with ≥ 2 comorbidities (62.8% hypertension, 9.3% diabetes, 1.7% obesity), median room air SaO2 95% (IQR 94-96), 63% receiving O2 and 11.8% Remdesivir. 74% of participants were simultaneously randomized to D or DB. There were not statistically significant differences in endpoints in participants not treated vs.treated with TDF/FTC: mortality 2.2%/4.0%, disease progression 23.6%/22.0%, deferred randomization to D or DB 6.7%/6.2%, mechanical ventilation (invasive or noninvasive) 22.5%/20.3%, days since randomization until discharge (median [IQR]) 7 [5,14]/6 [4,12], discharge before 28 days 91.9%/89.7%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 1.96 (0.55-7.01) for participants treated with TDF/FTC. Serious adverse events occurred in 6.18%/5.65% of participants not treated/treated with TDF/FTC. Adverse events leading to TDF/FTC discontinuation occurred in 2.26%. Conclusion: In this clinical trial of high-risk patients with COVID-19 TDF/FTC did not improve disease outcomes. Overall mortality was unexpectedly low.
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Background: Recent studies suggest that baricitinib added to dexamethasone may reduce mortality in hospitalized COVID-19 patients requiring supplemental oxygen Methods: In a multicenter open-label, pragmatic, randomized clinical trial in 25 hospitals in Spain we included symptomatic participants with SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance >60 mL/min, > 60 years or younger if they had at least two comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were initially randomized to receive or not tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). At any moment during the trial participants with room air 02 saturation < 95% and at least one increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increase of O2 requirements, mechanical ventilation or increase in medical therapy: steroid dose, need for starting tocilizumab) Results: Out of the 355 participants included in the trial 287 (80.8%) were randomized to D (n=142) or DB (n=145), 264 (91.9%) simultaneously with the TDF/FTC randomization and 23 (8.1%) later on. Median age 67 years (IQR 62, 73), male (65.5%), with median 8 days of symptoms (IQR 5-10), 28.6% with ≤ 5 days of symptoms, 100% hospitalized, 31.6% with one and 38.7% with ≥ 2 comorbidities (most common: 35.9% hypertension, 9.4% diabetes, 1.7 % obesity), 14.3% receiving remdesivir and 49.1% TDF/FTC. Endpoints in participants treated with D vs. those treated with DB favored DB without achieving statistical significance: mortality 4.9%/2.1%, disease progression 27.5%/24.8%, mechanical ventilation (invasive or noninvasive) 25.4%/23.4%, days since randomization until discharge (median [IQR]) 7 [5, 12]/7 [5, 13.5], discharge before 28 days 89%/94.2%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 0.51 (0.13-2.06) for participants treated with DB. Serious adverse events occurred in 9.9%/9.7% of participants treated with D or DB respectively. Adverse events leading to B discontinuation occurred in 3.45% of participants. Conclusion: In this clinical trial of high-risk patients with COVID-19 all disease outcomes favored baricitinb added to dexamethasone but differences did not reach statistical significance. Overall mortality was unexpectedly low.
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Background: Bone loss is a well-recognised complication of myeloma, affecting up to 90% of patients. It is associated with fractures, spinal cord compression and hypercalcaemia. 1,2 Myeloma patients are routinely prescribed zoledronic acid, which has been shown to prevent skeletal-related events, preserve bone density and prolong progression-free survival.3 At NBT, zoledronic acid is prescribed on a paper prescription chart, which is not routinely reviewed by a pharmacist This process is not in accordance with other therapy, which is prescribed on ChemoCare and clinically verified by a pharmacist prior to administration. Objectives • To assess the adherence of zoledronic acid prescribing at NBT against the South West Clinical Network (SWCN) protocol. • To identify areas for improvement in the prescribing of zoledronic acid for prevention of skeletal events. Standards: 100% of patients receiving zoledronic treatment should meet the following go-ahead criteria:4 • Acceptable bloods within seven days of treatment (creatinine, calcium, phosphate, magnesium) • Comprehensive dental examination. • Dose modification based on creatinine clearance. • Treatment deferred if hypocalcaemia or hypophosphataemia. Methodology: The audit was conducted over a one month period between 1/11/2020 and 30/11/2020. A total number of 58 prescriptions were included in the audit. The data collection sheet for the audit included;patient details, date of treatment and zoledronic acid dose. This information was extracted from the drug charts. The information system ICE was used to verify the blood results and validity period. Creatinine clearance was calculated using the Cockcroft and Gault equation. The medical notes were reviewed for evidence of dental checks. Data was recorded on Excel for further analysis by the pharmacist. Results: An overview of all four audit standards is shown in Figure 1. Two of the four audit standards were fully met (standards 2 and 4). 2% of patients (n= 1/58) did not receive an appropriate zoledronic acid dose adjustment based on renal function (standard 3). 36% (n=21/58) of patients did not have bloods within seven days of treatment (standard 1), however all of these patients had bloods within a month of treatment, in line with the Summary of Product Characteristic recommendations.5 Discussion and conclusion: The audit demonstrated that adherence to zoledronic acid prescribing guidelines is generally satisfactory;however several areas for improvement were identified. Feedback was provided to the haematology team and the following recommendations made: • Critical bloods must be done within one week of treatment. • Evidence of a dental examination must be clearly documented. • An approved app must be used for calculating creatinine clearance. • Introduction of a pharmacist clinical verification. • Zoledronic acid should be prescribed on ChemoCare, to assist with the above recommendations. Limitations: This audit was only carried out over a month which will only provide a snapshot of prescribing and results may have been impacted by the COVID-19 pandemic. It was difficult to find documentation for dental checks and treatment delays due to bloods and in some cases, information had to be verified by the prescriber.
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Acute inpatient management of patients with end-stage renal failure (ESRF) requiring anticoagulation is problematic. Low molecular heparins (LMWHs) and direct oral anticoagulants (DOAC) are convenient, but largely dependent on renal function for clearance . Vitamin K antagonists (VKAs) are suitable for long-term anticoagulation, but often not appropriate in hospital, where rapid adjustments may be required. Unfractionated heparin (UFH) infusion is the conventional alternative, but this requires intensive monitoring, often not available outside high dependency/ intensive care units. A weight-adjusted, unmonitored subcutaneous UFH regimen avoids these problems and has been successfully trialled but is not widely used. 1,2 This is a single-centre retrospective analysis of 48 patients treated with subcutaneous UFH at a dose of 250 UI/Kg twice daily for treatment or prevention of venous thromboembolism (VTE), between September 2020 and August 2021. All patients receiving this regimen were identified via pharmacy database. The aims of this study are to evaluate indication for use and to assess safety (bleeding) and efficacy (breakthrough thrombosis) in our cohort. All patients had renal impairment with a median creatinine clearance at time of prescription of 15 ml/min (range 4-48 ml/min, interquartile range 10.25). A third was on established renal replacement therapy. Overall, two thirds required anticoagulation for either atrial fibrillation (AF) or VTE treatment. In such patients, UFH was used for bridging to an oral agent and it was preferred over LMWH in view of reduced/deteriorating renal function. The remaining patients required anticoagulation for VTE prevention or for presurgical management, in view of known pre-existing pro-thrombotic conditions. One patient was incorrectly given subcutaneous UFH to manage subtherapeutic INR in the presence of a metallic heart valve. Collectively, 18 patients deceased during or within 6 months from admission. Twelve per cent experienced non-major/major bleeding. 3 Three deaths were directly attributed to major gastro-intestinal bleeding (only one case was confirmed radiologically). Non-major events included bleeding from surgical wounds ( N = 2) and skin cancer lesion ( N = 1). Only one breakthrough thrombosis was reported. No death was attributed to thrombosis (table 1). In conclusion, weight-adjusted UFH is an effective anticoagulant regimen. It was originally studied in VTE but appears to be effective in AF as well. The risk of bleeding is relatively high, but comparable to similarly ill patients (e.g. COVID19) receiving monitored UFH infusions. 4.