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Introduction: The association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. Data from the pre-pandemic era has demonstrated the use of tracheostomy for ventilator weaning [1]. However, the use of tracheostomy in COVID- 19 patients was a subject of discussion [2]. Nevertheless, evidence of the impact of tracheostomy on the outcome in critically ill COVID patients is still lacking. This study aims to evaluate the impact on Intensive Care Unit (ICU) outcome (survival) of tracheostomy in COVID- 19 ventilated patients. Method(s): Monocentric descriptive observational study. Demographic and clinical data, timing of tracheostomy and outcome (ICU mortality) from 1st January to 31st December 2021 were registered. Analysis of descriptive statistics for continuous variables and survival analysis (log rank test). Result(s): 115 patients were included (72% males), all mechanically ventilated, 7 (6%) were subjected to tracheostomy. The mean age was 67.2 years (range 36-84 years). The ICU mortality was 62% (71). The group of patients not submitted to tracheostomy had a mean survival time of 24.4 days (SD +/- 1.5) and median survival time of 22 days (SD +/- 1.7). The group of patients that were subjected to tracheostomy, the mean survival time was 68.5 days (SD +/- 12.2) and median survival time was 50 days (SD +/- 2). This comparison is significative (Log Rank test, p = 0.0001). Conclusion(s): The present study demonstrates a better survival likelihood of the tracheostomized subpopulation. Tracheostomy was only done in 6% of patients, which elucidates a need to further prospective, randomized studies to assess the impact on the outcome of tracheostomy in ventilated COVID19 patients.
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Role of asthma as a risk factor in severity and mortality in COVID-19 varies in literature. In 2020, 4CMortality score was published, which through 8 parameters in the initial evaluation (age, sex, comorbidity index Charlson, respiratory rate, peripheral oxygen saturation, renal function, Glasgow scale and C-reactive protein) stratified risk of in-hospital mortality from COVID-19 into low(0-3 points), intermediate(4-8), high(9-14) and very high(from 15). Our objective is to assess usefulness of 4CMortality in asthmatic patients admitted for COVID-19 and to verify the degree of correlation between the score and the mortality data and hospital stay. Observational retrospective study of asthmatic patients admitted for COVID-19 between March 2020 and March 2021. Statistical analysis is performed using Fisher's exact test(risk scale-death), ANOVA(risk scale-days hospitalization), and Kaplan Meier curve, considering statistically significant those results with a p<0.05. Sample of 99 patients, 18 in low risk group, 35 intermediate risk, 44 high risk and 2 very high risk. In terms of mortality, 7 deaths(high risk, 15.9%) and 2(very high risk, 100%), statistically significant (Fisher 17.07, p<0.0001). In terms of hospitalization days, median 7 days(low risk), 10(intermediate risk), 17 (high risk) and 5 (very high risk);statistically significant(F 6.37, p 0.001). In the survival analysis, median survival of 7 days(low-risk), 10(intermediate risk) and 19(high risk)(Log Rank 32.887, p<0.0001)(Fig 1). In conclusion, 4CMortality score is a good tool to establish the probability of poor evolution in asthmatic patients admitted for COVID-19 due to increased mortality and hospital stay.
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Background: The SARS-CoV-2 pandemic has had an unprecedented impact on healthcare systems, and cancer patients were amongst the most vulnerable. CONTACT is a national multidisciplinary study assessing the impact of the SARS-CoV-2 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). Method(s): A novel, mixed prospective and retrospective design, with retrospective case identification of both cohorts, and trainee-performed data collection. The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID cohort (07/01/ 2019-03/03/2019) were compared to a cohort diagnosed during the first wave of SARS-CoV-2 in the UK ('COVID' cohort, 16/03/2020-10/05/ 2020), with 12-month follow-up. Result(s): Among 984 patients (pre-COVID: N=483, COVID: N=501), across 96 hospitals, the COVID cohort were less likely to receive staging investigations other than CT scan (148/501, 29.5% vs 180/486, 37.2%;p=0.01). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (42/77, 54.5% vs 72/94, 76.6%, p=0.001) and increase in the proportion recommended neoadjuvant therapy (35/77, 45.5% vs 22/94, 23.4%, p=0.002). Among patients within a non-curative pathway, fewer patients were recommended (201/424, 47.4% vs 223/389, 57.3%, p=0.004) or received palliative therapy (87/424, 20.5% vs 103/389, 26.5%, p=0.045). Ultimately, fewer patients in the COVID cohort underwent resection surgery (29/501, 6.4% vs 45/483, 9.3%, OR 0.64, 95%CI: 0.37- 0.97, p=0.036), whilst more patients received no treatment whatsoever (347/ 501, 69.3% vs 286/483, 59.2% p=0.009). There was no difference in median survival between the COVID and pre-COVID cohorts, (105 days, IQR: 86-124 vs 130 days, IQR: 108-157, p=0.093). Conclusion(s): The CONTACT study confirms alarming reduction in the staging and treatment provided to patients with PDAC diagnosed during the SARS-CoV-2 pandemic. Restoration of cancer services to pre-pandemic standards must be urgently addressed.
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Purpose: Acute kidney injury (AKI) occurs in more than half of kidney transplant recipients (KTRs) with COVID-19. The longitudinal trajectory of kidney function is unclear. To study this, we compare mortality outcomes and long-term allograft function as measured by the change in serum creatinine (SCR) after hospital discharge between kidney transplant patients with SARS CoV-2 who experienced in-hospital AKI with who did not have AKI. Method(s): In this retrospective, multi-center study, we identified 149 KTRs who tested positive for SARS-CoV-2 between March 1st, 2020 and March 31st, 2021. Data from electronic medical records were retrieved and compared between KTRs without AKI and KTRs with AKI who were hospitalized with COVID-19. Creatinine was trended at 0,1,3,6, and 12 months. Result(s): A total of 149 COVID-19 infected KTRs were hospitalized. Of them, 102 (69%) had AKI with 45 (44.1%) in Stage 1, 9 (8.8%) in Stage 2 and 41 (40.2%) in Stage 3. Thirty-three patients died and 97% of them was in AKI group. Patients in AKI group had median survival time of 1.18 months, compared to more than 8 months in non-AKI group (p=0.002), Figure 1. Regression analysis for Intercept and slope were estimated by AKI groups, showing mild improvement in mean SCR over the 1 year at 2.2 mg/dL from peak SCR of 3.6 mg/dL, lowest eGFR 23.9 (SD 14.39) but didn't reach pre-AKI baseline in patients with AKI (1.8mg/dL), Figure 2. Conclusion(s): Patients in AKI group had higher mortality most of which was in the early period. There was mild improvement in creatinine over the following 12 months in AKI group but SCR didn't return to baseline. There with no significant change in slope of creatinine for non-AKI COVID patients.
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Background: Venetoclax (Ven) in combination with hypomethylating agents, such as azacitidine (Aza) and low dose cytarabine (LDAC) has been shown to be effective therapy in acute myeloid leukaemia (AML) and has become standard of care for newly-diagnosed patients unfit for intensive chemotherapy (DiNardo et al., 2020;Wei et al., 2019;Pollyea et al., 2020). Efficacy has also been shown in the relapsed/refractory (R/R) setting in more limited data sets (Báez-Gutiérrez et al., 2021;Pollyea et al., 2020, Stahl et al., 2020;DiNardo et al., 2019). Ven combination therapy has become widely used in newly-diagnosed patients in the UK since its approval during the COVID-19 pandemic as an alternative to intensive chemotherapy and subsequently for patients unfit for intensive therapy. Aims: We describe the characteristics and outcomes of patients with AML or high risk myelodysplastic syndrome (HRMDS) receiving Ven combinations in frontline and R/R settings to provide real-world insight into their use in UK clinical practice. Methods: A retrospective analysis was performed of all patients with AML or HR-MDS who received Ven combination therapy at University College London Hospital between April 2020 and September 2021. Patient demographics, treatment history and bone marrow results were obtained from electronic health care and laboratory records. Disease stratification and response assessments were made as per European LeukemiaNet (ELN) criteria (Döhner et al., 2017). Results: At the time of analysis, 95 patients received Ven combinations (61 as frontline treatment and 34 for R/R AML), with a median follow up of 14 months. The majority of patients in both groups had adverse risk ELN classification (70.5% of frontline patients, 64.7% of R/R) and received Ven-Aza (100% frontline and 91.1% R/R) (Table 1). The median ages were 72 and 59 years respectively. The incidence of composite CR/CRi was 70.5% in the frontline setting, with median duration of response (DoR) of 8.3 months and overall survival (OS) of 7.1 months. In R/R AML, the CR/CRi rate was 64.7%, median DoR 10.5 months and median OS 9.8 months. Four out of the 43 patients who achieved CR/CRi (9.3%) following frontline treatment and 9 of the 22 R/R (40.9%) patients proceeded to allogeneic stem cell transplant (alloSCT) post induction. The median survival for all patients who underwent alloSCT is not reached in this analysis. The highest CR/CRi rates were observed in intermediate risk patients (90.9% in frontline treatment, 71.4% in R/R), with lower rates in both favourable (80% and 66.7%) and adverse risk patients (65.1% and 59.1% respectively). The presence of NPM1 and IDH1/2 mutations were associated with high CR/CRi rates in both the frontline (85.7% and 84.6% respectively) and R/R groups (100% and 81.8%), with below average response rates seen in TP53 mutated AML (62% in frontline, 40% in R/R). Notable responses were seen in patients with RUNX1 mutations in both settings (77.8% frontline, 66.6% R/R). Summary/Conclusion: Our data describes real world effectiveness for venetoclax combinations as both frontline and salvage therapy in UK clinical practice, similar to that seen in clinical trials. This further contributes to our understanding of these therapies, in particular their use as a viable treatment option in R/R patients and as a bridge to alloSCT, and highlights the importance of further characterisation of genetic predictors of response to inform treatment decisions in real-world practice.
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Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.
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Introduction: The best treatment modality for lung cancer patients relies on survival estimates to weigh risks and benefits of treatments. However, patients who had pneumonectomy may have inherent oncologic or physiologic survival challanges. We aimed to analyzed the physiologic and survivability consequences of COVID-19 in these patients. Methods: A total of 111 of 898 patients(12.3%) who underwent resection in our clinic between 2001-2021 underwent pneumonectomy. Data of 70 patients were completed and the remaining 41 patients were excluded from the study for various reasons. The patients' survival, daily physical activities, comparison of preoperative and postoperative physical activity, and the general condition of those who had COVID-19 were questioned. Results: Sixty-seven patients were male (95.7%), three patients were female (4.3%). Forty patients (57.14%) had left pneumonectomy whereas 30 patients (42.85%) had right pneumonectomy. While 26 people (37.1%) were alive, 44 patients (62.9%) died. Four patients were suffered from COVID-19 infection and two of them died. Mortality was 50.0% whereas 1 (3.8%) and 2 (7.7%) patients had had extremely poorer and poorer physical activity compared to those of before pneumonectomy respectively, 9 patients (34.6%), 10 (38.5%) and 4 (15.4%) had same, better and extremely better physical activity compared to those of prior to pneumonectomy respectively. Estimated survival of all patients was 106 months (at the (95% confidence interval [CI]:58.69-153.30 months). The median survival of patients with right pneumonectomy was 103 months (95% CI:56.0-150.0 months) whereas it was 110 months (95% CI:45.5-174.5 months) in patients who had left pneumonectomy (p=0.859). Conclusions: The mortality due to Covid-19 was very high following pneumonectomy although the prevalence of COVID-19 seemed low in those patients. The physical activity was found to be worsened in small fraction of patients after pneumonectomy. Pneumonectomy seems safe and not debilitating in select patients even in Covid-19 era. [Formula presented] [Formula presented] Keywords: Covid-19, Pneumonectomy, Quality of Life
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Introduction: The COVID-19 pandemic presented many challenges to the delivery of healthcare, especially for those with lung disease.Our group recently reported that the rate of new lung cancer diagnoses declined by 35% during the first year of the COVID-19 pandemic (year 2020). The objective of the present study is to evaluate the changes in new lung cancer (LC) diagnoses during the 2 years of the pandemic compared to the pre-pandemic era, and its subsequent effect on survival of lung cancer patients. Methods: This is a retrospective chart review study including patients diagnosed with lung cancer between March 1st 2019 and February 28th 2022 at the Peter Brojde Lung Cancer Centre at the Jewish General Hospital, Montreal. We compared 3 cohorts: Cohort 1 (C1): March 1, 2019 to February 29, 2020 (pre-COVID). Cohort 2 (C2): March 1, 2020 to February 28, 2021 (1st year of COVID). Cohort 3 (C3): March 1, 2021 to February 28, 2022 (2nd year of COVID;reporting for 11 months). Results: A total of 404 patients were diagnosed with lung cancer throughout the three-year study: 130 in C1, 103 in C2 and 171 in C3. Using C1 as a baseline, we found that new diagnoses of LC declined by 21% in C2, and rose by 32% in C3. The incidence of metastatic lung cancer increased by 41% in 2021 compared to 2019 (96 cases vs 68 cases) and by 63% compared to 2020 (96 cases vs 59 cases). Of the 59 metastatic LC patients diagnosed in 2020, 31 (52%) died, whereas 28/68 (41%) died in 2019. The median survival for metastatic LC in the first year of the pandemic decreased compared to pre-COVID year (14.5 vs 8.7 months) (Table 1). Statistical significance has not been reached as follow-up time was not long enough for year 2020 (p=0.58). Conclusions: The present study represents interim data of our ongoing effort to evaluate the effect of the COVID-19 pandemic on our lung cancer patients. The pandemic has led to a significant decline in LC diagnoses in the first year, and a subsequent increase in diagnoses during the 2nd year. Unfortunately, these changes resulted in a trend towards decreased survival for our metastatic LC patients. The final survival analysis will require longer follow-ups and this data will be presented at the meeting. [Formula presented] Keywords: COVID-19, Retrospective, Survival
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Introduction: It was aimed to evaluate the efficacy, local control and survival in patients with inoperable primary or metastatic lung cancer who underwent stereotactic body radiotherapy (SBRT) using the Cyberknife-M6 (CK-M6) with lung optimized treatment (LOT) module. Methods: Ethics committee (no: 2018-7/6) and scientific research project (OUAP (T) 2019/1) approval were obtained. 23 lesions of 21 patients were treated between April 2019 to December 2020 at our department. The patients were immobilized in the supine position by wearing a Synchrony vest, with the hands at their sides. A planning 4D-CT was obtained in a free breathing modality. The gross target volumes was created both on the full-inhale and full-exhale phases and internal target volume (ITV) was created. By taking an image of patients on the treatment device, tracking modality was selected according to the visibility of the target. Zero-View tracking was applied in 10 patients, 1-View in 10 patients, 2-View in 1 patients. 3 to 5 mm margin added for planning target volume (PTV) according to tracking method. Median ITV and PTV was 9,38 (2-52,34) and 20,27 (9,25-82,7) cc, respectively. An InCise2 multileaf collimator optimized by the Monte Carlo algoritm was used in all patients. A pair of the orthogonal kV X-ray imaging systems were used for simultaneous target tracking. Median prescribed dose was 48 Gy in 4 fractions (30-54 Gy in 3-6 fractions) administered consecutively or every other day. Prescription isodose covering 95% of PTV was 82,5% (77,4-99,3). Median conformity and homogeneity index was 1,17 (1,02-1,77) and 1,22 (1,09-1,29), respectively. Median BED10 was 100 Gy (53,62-151,2) and median beam on time was 26 minutes (12-42). Results: Patients were evaluated on January 2022. The median follow-up was 21 months (2-33). The median age was 68 (53-80) and 40% of the cases were adenocarcinoma. Two patients diagnosed with radiologically. Median lesion size was 13 mm (9-27). SBRT was applied to 13 primary tumors, 3 lung metastases and 7 lymph nodes. At initial evaluation, complete, partial and stable response was found 30%, 65% and 5%, respectively. During the follow-up, 3 patients locally recurred at a median of 11 months (9-14). The median and one-year local recurrence free survival was 22 months, and 89%. Acute and late grade 1-2 pulmonary complications was seen in 10 patients in a median of 7 months (2-13). While the cause of death in 6 cases was existent cardiac morbidity, covid19 pneumonia, lung infection (2) and progression (2), it was unknown in 1 patient. The median and one-year survival was 23 months and 95%. Conclusions: LOT module of the CK-M6 Xsight lung tracking system allows for the application of fiducial-free motion management strategies. The advantage of our study is that the most appropriate tracking modality can be selected prospectively before treatment. In our study, excellent local control with a median survival of 23 months for primary and metastatic lung cancer. With a median treatment time 26 minutes, noninvasive CK-M6 based SBRT was efficient, safe and comfortable treatment in lung cancer. Keywords: lung cancer, Cyberknife-M6, stereotactic body radiotherapy
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Background: Vaccination against SARS-CoV-2 is effective in preventing severe forms of COVID-19, but there remain concerns about a reduced vaccine response in patients suffering from infammatory arthritides who are treated by immunosuppressive therapies. Objectives: We analysed the impact of bDMARDs on the humoral anti-SARS-CoV-2 vaccine response of patients followed in day hospitals. Methods: We studied the vaccine response after a complete vaccine regimen followed in day hospital in 5 French hospitals and treated with an intravenous bDMARD between September 2019 and August 2021. After obtaining their informed consent, we included patients with an anti-SARS-CoV-2 serology. They were considered non-responders if the antibody level detected was inferior to the threshold of positivity of the kit used. Results: 205 patients were included (148 females/57 males). The median age was 64 years (Interquartile Range [IQR] 56-71). 25 were treated with tocilizumab (TCZ), 36 with abatacept (ABA), 53 with infiximab (IFX) and 91 with rituximab (RTX). When considering both patients after a complete vaccination schema (2 doses, or 1 dose in case of prior COVID-19) and those with 1 booster dose, 34 patients (16.6%) were non-responders (2 [5.9%] treated by IFX, none treated by TCZ, 9 [26.5%] treated by ABA and 23 [67.7%] treated by RTX). In multivariate analysis, the only characteristics that signifcantly and independently differed between respond-ers and non-responders were last bDMARD and corticosteroid therapy at the time of 1st vaccination (Table 1). In RTX-treated patients, the delay from last infusion to 1st vaccine dose was signifcantly shorter in non-responders (median 4.3 IQR [2.9-6.1] months in non-responders versus 8.4 IQR [5.7-14.5] in responders, p=0.0007). Median survival, I.e. achieving a vaccine response in 50% of RTX-treated subjects, was achieved after 277 days (95CI [209-310]) in patients vaccinated with 2 or 3 doses (Figure 1). In ABA-treated patients, the delay from last infusion to 1st vaccine dose was not different between non-responders and responders. Conclusion: ABA and RTX alter the anti-SARS-CoV-2 vaccine response and were associated with nearly all vaccine non-responses in the present study. Cor-ticosteroid therapy was associated with a lower vaccine response regardless of its indication or the concomitant use of bMARD.
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Introduction. The Peruvian COVID-19 vaccination plan started on March 2021 and consists of three types of vaccines. After 8 months it has reached 55.18% of the target population with two dosis of vaccines and 3.5 million people have not yet received the 2nd dose. There is the need to estimate the mortality with the current vaccination plan because there is limited information of its effectiveness. Objective. To estimate the current effectiveness of the COVID-19 vaccination plan to prevent mortality in population above age 18. Methods. Matched cohorts case control study of hospitalized patients diagnosed of COVID-19 from February 9, 2020 through October 27, 2021. 107 410 subjects from the State's Peruvian Open Data National Platform were included from which 2254 dead hospitalized subjects selected had two vaccine doses and 2254 had not. Effectiveness was estimated by modelling survival method of Kaplan Mayer and the Cox (HR). Results. The estimated effectiveness of the vaccination plan was 80.4% (IC 95% 78.2% - 82.5%). The COVID-19 lethality rate in vaccinated was 17.5% vs 78.8% in non-vaccinated. The median survival time in the hospitalized vaccinated cohort was 42 days (IC 95%: 31-64), vs 7 days (IC 95%: 6-7) in non-vaccinated (p < 0.001). Conclusions. The vaccines utilized in the Peruvian program are highly effective to prevent mortality in hospitalized for COVID-19. Results might improve should coverage and completeness of two doses increase.
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BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a debilitating disease that can have a significant impact on a patient's quality of life. The aim of this study was to assess the longitudinal quality of life amongst those diagnosed with AAV using the EQ-5D instrument, which allows for calculation of quality-adjusted life years (QALYs.) METHOD: A total of 343 patients with AAV participated in this study, of which 191 (55.7%) were male, resulting in 2746 episodes. The EQ-5D-5L standardised instrument was used to evaluate health-related quality of life in the domains of mobility, self-care, usual activities, pain/discomfort, anxiety/depression and to generate a summary index score. Overall health was also rated using a visual analogue scale (0-100). EQ-5D questionnaires were completed during routine nephrology clinic attendances and through a vasculitis patient support smartphone app. We used a random effects model to control for multiple entries relating to individual patients. RESULTS: A lower quality of life was seen amongst those with AAV (median index value 0.80, overall population average 0.856). The mean visual analogue scale score was 75.6 ± 17.3 (overall population average 82.8, Fig. 1). Patients' pain and discomfort level (mean 1.95) was most affected while self-care (mean 1.33) was least affected (Fig. 1). An increase in BVAS tightly correlated with a reduction in quality of life. Using the random effects model, the index score was seen to decrease with increasing age with a 2.7% reduction in index score per decade. A 7% reduction in index score was seen during periods of disease activity compared with periods of remission. Patients with end-stage kidney disease requiring dialysis had an 8% reduction in index score. A reduced quality of life was seen following COVID-19 lockdown with a 5% reduction in index score seen. Using a median survival rate of 6.16 years for patients with small vessel vasculitis, we calculated the QALYs for this population as 4.9 years. CONCLUSION: We have defined for the first time the EQ-5D index value over the full disease course in patients with AAV. Notably, we have identified a reduction in quality of life during periods of disease activity. Other studies have demonstrated a reduction in quality of life during active disease using the AAV-PRO questionnaire and the Medical Outcomes Study Short Form-36. A decrease in work productivity has also been noted. Previously reported mean index values of 0.72 and 0.76 were lower than our observed values, although both are significantly reduced compared with population norms. In conclusion, this research highlights the negative impact of AAV on patients' lives.
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Purpose/Background: Colonic large cell type neuroendocrine carcinoma (LCNEC) is a rare type of neuroendocrine tumor with only 13 reported cases in the literature. Due to their rarity, there is currently no standardized management. Hypothesis/Aim: We present a case of colonic LCNEC presenting with obstruction requiring urgent surgical intervention. Methods/Interventions: A 43-year-old male presented to the emergency department with several days of abdominal pain and constipation for 48 hours. Physical exam revealed diffuse abdominal pain. A computed tomography scan of the abdomen and pelvis was concerning for a distal transverse colon mass causing obstruction and multiple hepatic lesions. (Figure 1, A-C). The patient was taken to the operating room for urgent exploration and was found to have a transverse colonic mass was identified just proximal to the splenic flexure. Resection was performed and a side-to-side anastomosis of the right and descending colon was created with a protective loop ileostomy. Liver lesions were biopsied. Pathologic analysis revealed invasion into the peri-colorectal tissue consistent with a T3 lesion. Lymphovascular (LV) and perineural invasion were also present. Seven out 27 total lymph nodes (LN) were positive for cancer and the hepatic nodule was positive for cancer. Histological analysis revealed large cells with prominent nucleoli, abundant cytoplasm, marked pleomorphism, frequent mitosis, and apoptotic bodies consistent with LCNEC (Figure 1, D). Immunohistochemistry showed that the tumor was positive for AE1/1, CK 20, synaptophysin, and chromogranin A. The Ki-67 index was over 95%. Results/Outcome(s): Postoperatively the patient was started on a regimen of cisplatin and etoposide. He was readmitted during his second cycle of chemotherapy with high ileostomy output, E. coli bacteremia and COVID-19. Repeat imaging showed progression of his disease (Figure 1, E). The patient had a precipitous decline in helath and decided to pursue comfort measures. He had a survival time of 3 months after diagnosis. Limitations: The limitation of this study is that it is a single case. Conclusions/Discussion: NECs account for 0.6% of all colorectal cancers with LCNECs responsible for ~0.2% of NECs. At the time of diagnosis, LV invasion, LN spread, and distant metastases are usually present, which coincides with a median survival of 4-16 months. First line treatment for localized colorectal NECs is primary resection. The National Comprehensive Cancer Network (NCCN) guidelines recommend combined cisplatin and etoposide may be appropriate for locally advanced tumors;however, multiple studies have shown to show no improvement in median survival. Our patient presented with obstruction requiring surgical intervention, which extended the patients life by 3 additional months. Further research to define the best course of treatment for advanced colonic LCNECs will be difficult due to the infrequency of the disease. (Figure Presented).
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Introduction: Solid Organ Transplants (SOT) is at increased risk of Coronavirus Disease 2019 (COVID-19) infection, which may result in acute graft dysfunction and even death. While the disease has been well studied in the general population, it is not the case in renal transplant recipients. The poor immunological response of the vaccine in postrenal transplant patients, the emergence of newer strains, and the possibility of a third wave in India, makes it even more important to know more about the course and outcome of the disease in post renal transplant patients. Aim: To evaluate the demographics, clinical presentation, biochemical profile, course of hospitalisation in post kidney transplant patients with COVID-19. Materials and Methods: This retrospective observational study study with 18 patients was conducted in Madurai Medical College, Tamil Nadu, India for duration of four months, from May 2021 to August 2021 and data collection from May 2021 to July 2021 and data analysis in August 2021. All post kidney transplant patients having evidence of COVID-19 were included. Detailed clinical history, biochemical profile, radiological findings, treatment, and final outcomes were collected and compared. Non parametric statistical tests were used, in addition to Chi-square test and odds ratio. Kaplan-Meier plot was used for survival analysis. Results: The most common presentation was fever 15 (83.3%), followed by cough 10 (55.6%). C-reactive Protein (CRP) {65 mg/L (11.48-94.48)}, D-dimer {0.72 mcg/mL (0.59-1.1)}, serum creatinine {3.5 mg/dL (2.12-5.93)}, and platelet count {200,000 cells/cu.mm (1.75-2.22)} and showed statistically significant (p<0.05) association with the outcome. About 15 (83.3%) patients developed Acute Kidney Injury (AKI). Seven patients (38.9%) had stage three AKI necessitating haemodialysis, of which six did not survive. The median survival time was 22 days, with 95% confidence interval (19.792-24.208), with case fatality rate of 33.3% Conclusion: Postkidney transplant patients are at high risk of contracting COVID-19. CRP, D-dimer, serum creatinine, platelet counts, and arterial oxygen saturation may serve as prognostic markers. Dialysis may be required in view of high incidence of AKI and acute graft dysfunction, though the outcome seems dismal in such patients. Hence, the need for early hospitalisation and more effective treatment protocol is essential to improve outcome.
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Background: During the COVID19 pandemic, many centres in the UK, shifted towards utilising hypofractionated radiotherapy (RT) to pancreas. We aim to report the UK experience hypofractionated (3-5 fractions) RT to the pancreas from 7 centres in the UK. Rates of toxicity, progression, death and potential prognostic factors were assessed. Univariate and multivariate Cox proportional hazards analyses were performed. Results: 92 patients from 7 centres were included in the analysis (median age 71 (range 49-88). 90% had performance status of 0-1. 66% had locally advanced disease. 53% had RT delivered over 3- 5 fractions (n = 49, median: 30Gy/5f, range:30- 40Gy in 3-5f). The rest had 15-fraction RT with or without concurrent chemotherapy (n = 43, median: 45Gy/15f, range: 36-45Gy/15f). Induction chemotherapy (CT) was used in 64% (FOLFIRINIOX -42/59). Median follow-up was 13 months from first treatment (induction CT or RT). Median overall survival (OS) among all patient was 17 months, (95% CI-14.5-19.5 months). On multivariable analysis, induction CT was the only predictor of improved PFS (median survival (MS) 12 vs 5 months;hazard ratio [HR] 0.23;95% confidence interval [CI]: 0.12-0.44, p < 0.001) and OS (MS 24 vs 11 months;HR 0.15;95% CI: 0.07 - 0.34, p < 0.001). There were no deaths. 4 patients had grade 3+ toxicities (transaminitis, cholecystitis and gall bladder perforation, small bowel obstruction and diarrhoea) -all had concurrent CT. Conclusions: Our survival outcome appears to be comparable with published data from CT + concurrent chemoradiotherapy. Induction CT appears to improve outcome. Careful selection of patients can help maximise advantage in this patient population.
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Introduction: As defined by MB-CPK, hsTn-I, MB, or EKG and/or cardiac echo abnormalities, cardiac injury (CI) determines a median survival time (MST) of 10 days for hospitalized COVID patients (HCPs). HCPs without defined CI have an MST beyond 39 days (Huang, et al., see Figure). Hypertension (HTN) presents in 17-41% of HCPs in various studies, with COVID mortality independent of HTN. Therefore, a randomized clinical trial (RCT) is proposed for HCPs with CI and incidental BP elevation to compare IV isosorbide dinitrate (ISDN) with usual anti-HTN care (UC). Vasodilatory ISDN lowers BP, and has been proposed an an anti-SARS-CoV-2 drug. Others report improved survival of ISDN treated Coxsackie B3 virus-infected mice as evidence for anti-viral activity. The endpoint for this CI RCT pilot of 100 ISDN-treat HCPs and 100 UC controls is mortality. Secondary endpoints are interval biomarkers to dissect ISDN anti-viral action. Methods: Log-rank analysis was performed with 1:1 allocation. Accrual time was 180 days with a 60-day follow-up. Power was 0.8 with a type I error of 0.05. Results: For 200 total subjects, an MST greater than 14.9 days in the ISDN arm was significant if UC stays at 10 days (see Figure). Conclusions: Testing repurposed ISDN as a COVID drug is feasible. A successful pilot with improved MST suggests ISDN has anti-SARS-CoV-2 action, since COVID mortality is independent of HTN. Biomarkers could include viral clearance, oxygenation, D-dimer, IL-6, LDH, as well as platelet and lymphocyte counts. The need to treat HCPs with elevated BP per guidelines permits study entry. Cross-over treatment occurs if a regimen fails. Immunomodulators and remdesivir are administered per COVID treatment guidelines for all HCPs. IV ISDN, bolused and/or infused, avoids 1 pass hepatic effects. IV IDSN is approved in most countries, but not in the USA or Canada. A successful pilot would permit larger IV ISDN RCTs as IND RCTs, and can serve as a template for other treatments for HCPs with defined CI.
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Introduction Since March 2020, the New York City hospitals have experienced a tremendous surge of COVID-19 cases. Our hospital admitted 877 patients in a 2-week period, from March 15 to Apr 1, 2020. The exact mechanism of how COVID-19 causes vascular injury is unclear but some experts attribute it to widespread vascular inflammation[2,3]. The limited understanding of the hypercoagulable mechanism has limited our treatment techniques. To date, whether therapeutic anticoagulation is the right choice in regard to optimal management of patients with COVID-19 in suspected but not confirmed DVT (deep vein thrombosis) or PE (pulmonary embolism) is still a question[4]. Method We performed a retrospective observational cohort analysis of 145 adult ICU patients at an acute care teaching hospital located in Queens County, New York between March 15, 2020 to April 1, 2020. The study was approved by IRB. All patients >18 years of age with confirmed SARS-CoV-2 infection and determined to require admission to intensive care units between March 15, 2020 and April 1, 2020, inclusive of those dates, were included in the investigation, with the exclusion of pregnant patients. All data was collected from the electronic health record (Allscripts) and was compiled in REDCap software for data encryption. During that study period, therapeutic anticoagulants were used in hospitalized patients with COVID-19 with high clinical risk or suspicion for venous thromboembolism (VTE). As per hospital protocol, heparin continuous infusion with a target activated partial thromboplastin time of 50 to 70 seconds or enoxaparin 1mg/kilogram(kg) twice a day for creatinine clearance (CrCl) above 30 ml/min or once a day for CrCl below 30 ml/min were used to achieve therapeutic anticoagulation. The primary outcome of the study was 28-day in-hospital mortality for critically ill patients affected by COVID-19 with or without the use of therapeutic anticoagulation. Covariates included in analysis were hypertension, diabetes, hyperlipidemia, cardiac history, and use of antiplatelet and anticoagulant medications prior to admission. Statistical analysis was done using R version 4.0.2. Results Out of 145 ICU patients, 61 received therapeutic anticoagulation. Kaplan-Meier survival curves show the survival probability with respect to days after admission for the two groups (those who used anticoagulant therapeutic drugs and those who didn't) using 28-day in-hospital mortality.(Fig 1) Median age for patients was 61 years for patients who didn't receive therapeutic anticoagulants compared to 60 years for patients who received therapeutic doses. The mean D-dimer among patients who received therapeutic anticoagulation was 20462 ng/ml (D-dimer units) compared to 7872 ng/ml for those who did not. The median number of days of survival for those who did not take anticoagulant therapeutic drugs is 10 days, while the median for those who did take anticoagulant therapeutic drugs is 25 days. After adjusting for hypertension, diabetes, hyperlipidemia, cardiac history, home antiplatelet medication use and continuous response for peak d-dimer levels, the results also show that there is a causal effect of 22.2 % decreased risk of 28-day in-hospital mortality if one received the therapeutic anticoagulant in the hospital. Conclusion Our findings suggest that there is a significantly higher median survival time in critically ill patients who received therapeutic anticoagulants in the hospital compared to those who didn't. However, our study is limited by observational nature, possible unobserved confounding, lack of metrics to classify illness severity as well as lack of evidence based decision guideline in initiation of therapeutic anticoagulation. There is an urgent need for further evidence-based studies like clinical trials which are necessary to provide specific guidelines for use of therapeutic anticoagulants in patients with COVID-19 infection. References 1. Becker RC. COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis. 2020;50(1):54-67. 2. Tay, M.Z., Poh, C M., Rénia, L. et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 20, 363-374 (2020). 3. Lisa K. Moores, Tobias Tritschler, et al. Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report, Chest, Volume 158, Issue 3, 2020, Pages 1143-1163, ISSN 0012-3692. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Background: De novo nucleotide synthesis is necessary to meet the enormous demand for nucleotides, other macromolecules associated with acute myeloid leukemia (AML) progression 1, 2, 34. Hence, we hypothesized that targeting de novo nucleotide synthesis would lead to the depletion of the nucleotide pool, pyrimidine starvation and increase oxidative stress preferentially in leukemic cells compared to their non-malignant counterparts, impacting proliferative and differentiation pathways. Emvododstat (PTC299) is an inhibitor of dihydroorotate dehydrogenase (DHODH), a rate-limiting enzyme for de novo pyrimidine nucleotide synthesis that is currently in a clinical trial for the treatment of AML. Objectives: The goals of these studies were to understand the emvododstat-mediated effects on leukemia growth, differentiation and impact on Leukemia Stem Cells(LSCs). Comprehensive analyses of mitochondrial function, metabolic signaling in PI3K/AKT pathways, apoptotic signatures, and DNA damage responses were carried out. The rationale for clinical testing emvododstat was confirmed in an AML-PDX model. Results: Emvododstat treatment in cytarabine-resistant AML cells and primary AML blasts induced apoptosis, differentiation, and reduced proliferation, with corresponding decreased in cell number and increases in annexin V- and CD14-positive cells. Indeed, the inhibition of de novo nucleotide synthesis compromises the dynamic metabolic landscape and mitochondrial function, as indicated by alterations in the oxygen consumption rate (OCR) and mitochondrial ROS/membrane potential and corresponding differentiation, apoptosis, and/or inhibition of proliferation of LSCs. These effects can be reversed by the addition of exogenous uridine and orotate. Further immunoblotting and mass cytometry (CyTOF) analyses demonstrated changes in apoptotic and cell signaling proteins (cleaved PARP, cleaved caspase-3) and DNA damage responses (TP53, γH2AX) and PI3/AKT pathway downregulation in response to emvododstat. Importantly, emvododstat treatment reduced leukemic cell burden in a mouse model of AML PDX ( Complex karyotype, mutation in ASXL1, IDH2, NRAS), decreased levels of leukemia stem cells frequency (1 in 522,460 Vs 1 in 3,623,599 in vehicle vs emvododstat treated mice), and improved survival. The median survival 40 days vs. 30 days, P=0.0002 in primary transplantation and 36 days vs 53.5 days, P=0.005 in secondary transpantation in a PDX mouse model of human AML. This corresponded with a reduction in the bone marrow burden of leukemia and increased expression of differentiation markers in mice treated with emvododstat (Fig. 1). These data demonstrate effect of emvododstat on mitochondrial functions. Conclusion: Inhibition of de novo pyrimidine synthesis triggers differentiation, apoptosis, and depletes LSCs in AML models. Emvododstat is a novel dihydroorotate dehydrogenase inhibitor being tested in a clinical trial for the treatment of myeloid malignancies and COVID-19. Keywords: AML, emvododstat, DHODH, apoptosis, differentiation References: 1 Thomas, D. & Majeti, R. Biology and relevance of human acute myeloid leukemia stem cells. Blood 129, 1577-1585, doi:10.1182/blood-2016-10-696054 (2017). 2 Quek, L. et al. Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. The Journal of experimental medicine 213, 1513-1535, doi:10.1084/jem.20151775 (2016). 3 Villa, E., Ali, E. S., Sahu, U. & Ben-Sahra, I. Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides. Cancers (Basel) 11, doi:10.3390/cancers11050688 (2019). 4 DeBerardinis, R. J. & Chandel, N. S. Fundamentals of cancer metabolism. Sci Adv 2, e1600200, doi:10.1126/sciadv.1600200 (2016). [Formula presented] Disclosures: Weetall: PTC therapeutics: Current Employment. Sheedy: PTC therapeutics: Current Employment. Ray: PTC therapeutics: Current Employment. Andreeff: Karyopharm: Research Funding;AstraZeneca: Research Funding;Oxford Biomedica UK: Research Funding;Aptose: Consultancy;Daiich -Sankyo: Consultancy, Research Funding;Syndax: Consultancy;Breast Cancer Research Foundation: Research Funding;Reata, Aptose, Eutropics, SentiBio;Chimerix, Oncolyze: Current holder of individual stocks in a privately-held company;Novartis, Cancer UK;Leukemia & Lymphoma Society (LLS), German Research Council;NCI-RDCRN (Rare Disease Clin Network), CLL Foundation;Novartis: Membership on an entity's Board of Directors or advisory committees;Senti-Bio: Consultancy;Medicxi: Consultancy;ONO Pharmaceuticals: Research Funding;Amgen: Research Funding;Glycomimetics: Consultancy. Borthakur: ArgenX: Membership on an entity's Board of Directors or advisory committees;Protagonist: Consultancy;Astex: Research Funding;University of Texas MD Anderson Cancer Center: Current Employment;Ryvu: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy.
ABSTRACT
Patients with secondary AML or MDS derived AML have poor outcomes compared to de-novo AML. The benefits of intensive chemotherapy without anticipated transplant consolidation have been previously doubted. Outcomes in USA trial centres have not often been closely replicable in real world settings. From November 2018 CPX-351 has been available in the UK for secondary AML, therapy related AML, AML with MDS related Karyotype (AML-MRC) and licensed but not funded for AML with myelodysplastic related changes. Objectives Here we report our experience specifically on patient outcomes and toxicity across 5 Hospitals in West Midlands, UK Methods Patients receiving CPX 351 outcomes were evaluated retrospectively from 2018 to 2021. Baseline genetics, CPX 351 indications, patient's comorbidities, overall survival, remission status, number of cycles delivered, early mortality, reasons for early discontinuation, intensive care admission and time for neutrophil recovery (>0.5) was recorded. Time-to-event outcomes reported here are from a data cut on 01-06-21 Results In a total cohort of 57 patients baseline characteristics are shown on table 1 and compared with the original trial CPX-351 group. Median follow up was 376 days (range 21 to 1248 days). The mean age was 63, 17 patients were under 60, 31 males and 26 females. The most common indication for CPX-351 was AML with antecedent MDS/MPN 51% (N=29), therapy related 14% (N=8), MDS related karyotype (AML-MRC) 19% (N=11) and 16% (N=9) other patients. Mean Charleston co-morbidity score was 2.7 (range 0-6), 10.5% (N=6) had previous non myeloid malignancies, 8.7% (N=5) had prior ischaemic heart disease, only 3.5% (N=2) had ejection fractions under 50%. The most common mutations were TP53 21% (N=12), ASXL1 15.7% (N=9), TET2 15.7% (N=9), IDH2 10.5% (N=6), RUNX1 10.5% (N=6), SRSF2 7% (N=4), JAK2 3.5% (N=2), FLT3 5% (N=3), NPM1 5%(N=3) and IDH1 5% (N=3). MRC cytogenetic risk was adverse in 19 patients (33%), intermediate in 35 patients (61%) and favourable in 3 patients (5%). 30 patients (53%) had adverse European Leukaemia Network classification, 17 (30%) had intermediate and 10 (17%) had favourable. 30-day mortality was 3/57 (5%), 60-day mortality was 6 (10.5%) comparable to the 5.9% and 10.6% rates for the original trial. 9% or 5/57 patients were admitted to ITU with 2 survivors beyond 60 days. Neutropenic fever requiring antibiotics was 100% whereas only 5/57 (9%) had radiological evidence of fungal infection. Only one patient died from COVID 19. The mean time to neutrophil recovery was 35 days with a range of 12 to 84 days. 29 patients completed 1 cycle, 25 completed 2 cycles, only 3 completed 3 cycles. The reasons for stopping were death, refractory disease, drop in performance status, alternative chemotherapy chosen or moving to transplantation (39%). Composite remission rate including CRi was 61% 36/57, adverse ELN group demonstrated 50% 15/30, intermediate 76% 13/17 and favourable 80% 8/10. Mutated P53 was associated with a 50% 6/12 rate whereas in wild type P53 the remission rate was 60% 30/45. Overall median survival from diagnosis was 429 days [95% CI 274 to 788 days]. To compare with the original trial, we removed the under 60s and those with less than 1 year follow up, in this cohort of 30 patients the median survival was 289 days (9.5 months) with 95% CI of 255 to 476 days. P53 mutated patients had an estimated median survival of 257 days versus wild type p53 with 524 days hazard ratio of 2.418 (CI 1.077 to 5.248) with p value of 0.032. Median survival for ELN groups was 373 days (adverse), 413 days (intermediate) and not reached for favourable. Of the 36 patients who achieved a remission, 22 went on to receive an allogenic transplant with follow from 254 to 1248 days, median survival estimated 706 days (95% CI 429-not reached). Patients in remission who haven't received a transplant have a similar estimated survival of 788 days (305-not reached) pending longer follow up. Conclusion This is the first UK multicentre analysis to show comparable results to the landmark trial ( edian survival 9.5 months in equivalent cases). The improved overall remission rate 61% versus the 47% in the trial and the longer median survival 14 months versus 9.5 months in the trial is expected given the younger age and increase in favourable risk genetics. This study therefore supplies further data of CPX-351 efficacy in younger patients not included in the original studies and may now be used as a standard comparator arm. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
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Background: Peripheral artery disease (PAD) is a major challenge worldwide and endovascular revascularization is an important component of treatment that is affected by COVID-19 restrictions. Purpose: Here, we evaluated the impact of COVID-19 restriction on angioplasty service and outcome of patients undergoing lower limb angioplasty. Methods: Consecutive patients undergoing endovascular revascularisation between August 2018-March 2021 in a UK district general hospital were analysed retrospectively. Indications for angioplasty of all patients were discussed and agreed upon in multi-disciplinary teams. We compared time from referral to angioplasty, patient and procedural characteristics, technical success, peri-procedural complications, and outcome (wound healing, major amputation, target lesion revascularization, death) in patients treated 'before' and after February 2020 (during COVID-19). Results: One hundred nineteen patients were treated 'before' (92% critical limb ischaemia [CLI];60% diabetes mellitus) and 72 were treated 'during COVID-19' (96% CLI;61% diabetes mellitus). While the total monthly number of patients treated did not change, the number of outpatients treated as day cases increased (40% to 72%) and overnight stays for social reasons decreased (16% to 10%). Treatment of hospitalized patients decreased from 44% to 18%. The percentage of outpatients treated at <14 days after referral increased from 39% to 63% and hospitalized patients treated <5 days from 47% to 54%. Neither COVID-19 nor time to procedure affected wound healing (p(log Rank) = 0.451;median time to healing 168±l25 days) and amputation free survival (p(log Rank) = 0.924;median survival 368±l30 days) in all CLI patients significantly. However, amputation-free survival was significantly worse in hospitalized as compared to outpatients (p(log Rank) <0.001;median survival 155±l20 vs 368±l30 days) with similar wound healing in those that survived (p(log Rank) = 0.340;median time to wound healing 168±l25 days). Of note, the known causes of death were sepsis (32%), pneumonia (18%), COVID pneumonia (18%), cardiac (16%) and stroke (8%). Conclusions: Adapting to COVID-19 restriction we maintained a safe and effective angioplasty service while shortening waiting times. Very high mortality rates in patients after hospitalization indicated that CLI need to be treated much earlier and more aggressively to avoid disease progression requiring hospitalization.