scholarly journals REcovery and SURvival of patients with moderate to severe acute REspiratory distress syndrome (ARDS) due to COVID-19: a multicentre, single-arm, Phase IV Itolizumab Trial: RESURRECT

2021 ◽  
Author(s):  
Raveendra KR ◽  
Chirag Rathod ◽  
Rahul Darnule ◽  
Subramanian Loganathan ◽  
Sarika Deodhar ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Oxygen Therapy ◽  
Ordinal Scale ◽  
Tertiary Hospitals ◽  
Post Infusion ◽  
Secondary Analyses ◽  
Grade 3 ◽  
Treatment Safety ◽  
Common Teaes

Objective: To evaluate safety and efficacy of Itolizumab in hospitalized COVID-19 patients with PaO2/FiO2 ratio (PFR) ≤200 requiring oxygen therapy. Design: A multicentre, single-arm, Phase-4 study with a treatment period of 30-Days and an extended follow-up period of 90-Days. Methods: Hospitalized adult patients (n=300) with SARS-CoV-2 infection, with PFR ≤200, oxygen saturation ≤94% and ≥1 elevated inflammatory markers were included from 17 COVID-19 specific tertiary hospitals in India. Patients received Itolizumab infusion 1.6 mg/kg and were assessed for 1-month and then followed up to Day-90. Results: Day-30 post-treatment safety/efficacy results and Day-90 mortality results are presented. Primary outcome measures: incidence of severe acute infusion-related reactions (IRRs) (≥Grade-3) was 1.3% and mortality rate at 1-month was 6.7% (n=20/300). Key secondary analyses: Mortality rate at Day-90 was 8.0% (24/300). 91.7% patients came off the oxygen therapy within Day-30 of treatment. By Day-7, most patients had stable/improved SpO2 without increasing FiO2. Mean PFR improved by 50% by Day-7 (p<0.001) and the trend remained consistent till Day-30. Median time of recovery was 8 days. Cumulatively, at Day-30, 260(86.7%), 256(85.3%), 132(44.0%), 113(37.6%) and 32(10.7%) patients showed >1-point, >2-point, >3-point, >4-point and 5-point improvement on the modified COVID-19 8-point ordinal scale and worsening of symptoms by >1 point, >2 points and 3-points was seen in 26(8.7%), 20(6.7%) and 6(2.0%) patients, respectively. CRP, D-dimer, LDH and serum ferritin levels significantly decreased (p≤0.01) compared with baseline. IL-6 and TNFα levels also decreased 48-hours post-infusion. Overall, 123 treatment-emergent adverse events (TEAEs) were reported in 63 patients, most being Grades 1-3. Most common TEAEs were IRRs and lymphopenia; most common serious TEAEs were septic shock, worsening of ARDS and respiratory failure. No deaths were attributable to Itolizumab. Conclusion: Itolizumab shows no new safety concerns and suggests a mortality and recovery benefit at 1-month in hospitalized COVID-19 patients requiring oxygen therapy.

Overall survival results for durvalumab and savolitinib in metastatic papillary renal cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 619-619 ◽  
Author(s):  
Cristina Suarez Rodriguez ◽  
James M. G. Larkin ◽  
Poulam Patel ◽  
Begona Pérez Valderrama ◽  
Alejo Rodriguez-Vida ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Cancer ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Treatment Naïve ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3 ◽  
Treatment Safety

619 Background: There is a strong rationale for investigating MET and PD-L1 inhibition in metastatic papillary renal cancer (PRC). We previously reported response rates (RR) and progression free survival (PFS) for savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) together. Here we report overall survival (OS) data available 12 months after the last patient was enrolled. Methods: This single arm phase I/II trial explores durvalumab (1500mg Q4W) and savolitinib (600mg OD) together in PRC, with a 4wk savolitinib run in. Treatment naïve or previously treated patients with metastatic PRC were included. Confirmed RR (RECIST v1.1), PFS, tolerability (CTCAE v4.03) and overall survival (OS) were analysed. MET and PD-L1 biomarkers were explored (NCT02819596). Results: 42 patients were enrolled with 41 receiving at least one dose of study treatment. Safety and efficacy analyses were performed on these 41 patients. The median follow up was 14.3 months. IMDC good, intermediate and poor risk disease occurred in 29%, 63%, and 7% of patients respectively. Overall confirmed RR was 27% while median PFS was 4.9 months (95% CI: 2.5 – 12.0 months). Median OS was 12.3 months (95% CI: 5.8 – 21.3 months). Confirmed RR and median OS in the previously untreated cohort (N=27) were 33% and 12.3 months (95% CI: 4.7 – not reached (NR) months) respectively. Treatment related Grade 3/4 toxicity occurred in 34% of patients. No new safety signals were seen. PD-L1 and MET expression were not associated with higher RR (25% and 40% respectively) or longer OS. Conclusions: The combination of savolitinib and durvalumab has clinical activity in PRC and outcomes were not enhanced in biomarker positive cancers. Clinical trial information: NCT02819596.

scholarly journals Therapy of Paediatric B-ALL with a Fast Off Rate CD19 CAR Leads to Enhanced Expansion and Prolonged CAR T Cell Persistence in Patients with Low Bone Marrow Tumour Burden, and Is Associated with a Favourable Toxicity Profile

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 225-225
Author(s):  
Sara Ghorashian ◽  
Anne Marijn Kramer ◽  
Shimobi Onuoha ◽  
Gary Wright ◽  
Jack Luke Bartram ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Magnetic Bead ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T ◽  
Post Infusion ◽  
Grade 3

Introduction: The CARPALL study (NCT02443831) employed a novel CD19CAR (CAT-41BBz CAR) with a faster off rate than the Kymriah FMC63-41BBz CAR (CAT 3.1x10-3s-1, FMC 6.8 x 10-5s-1), with equivalent on-rate (CAT 2.2 x 105, FMC 2.1 x 105). We herein report updated outcomes and CAR T cell persistence with an additional 6 months follow up from a submitted manuscript (Ghorashian et al., Nat Med, submitted) Methods: Patients aged &lt;25 years with high risk, relapsed CD19+ B-ALL were eligible on this multi-centre, open label, non-randomised phase I study of autologous CAT-41BBz CAR T cells. Patients were followed to a data cut-off of 07/18/2019. CAT-41BBz CAR T cells were generated by magnetic bead activation of leucapheresed PBMCs, lentiviral transduction, followed by bioreactor expansion and magnetic bead removal prior to cryopreservation. All patients received lymphodepletion (fludarabine + cyclophosphamide) followed by 1x106/kg CAR T cells. Presence of CAR T cells in the blood and bone marrow (BM) was assessed (flow cytometry and qPCR) monthly for 6 months, then 6 weekly to 1 year and then 3 monthly. BM MRD was assessed (IgH qPCR, flow cytometry) at the same time-points up to 2 years to establish durability of responses as a stand-alone therapy. Primary end-points were incidence of grade 3-5 toxicity and the proportion of patients achieving molecular remission. Results: Of 17 patients recruited, 14 were treated due to manufacturing failure in 3 patients.The median age was 9 years (range 1-19 years). All patients had advanced ALL with a median of 4 prior therapy lines. 10 of 14 patients (71%) had relapsed post allogeneic SCT. Prior to lymphodepletion, 4 patients had &gt;5% BM disease, 6 had disease between 5x10-2and 1x10-5, 4 were BM MRD negative having had recurrent isolated CNS disease. Median transduction efficiency was 31% (range 16.5 to 96.4%). 12/14 treated patients received the anticipated dose of 1x106CAR T cells/kg (2 received 0.9x106/kg). Considering all evaluable patients, (n=14 for CAR T cell persistence by qPCR, n=13 by flow) the geometric mean of Cmax was 128 912/µg DNA and of the area under the curve between D0 and D28 was 1,721,355 copies/ µg DNA (Table 1). At the point of maximal expansion, a median of 35% of circulating T cells were CAR+. Median half-life was 34 days (range 3-102). CAR T cells continued to be detectable by qPCR in 11 of 14 (79%) patients at last assessment and by flow cytometry up to 30 months post infusion in 8 of 13(61%). Median duration of CAR T persistence by flow was 261 days (range 7-917). 3 patients failed to have persistence of CAR T cells beyond 1 month. T cell mediated anti-CAR specific cytotoxic activity was detected in 2/2 evaluable patients. Updated persistence data will be presented at the meeting Cytokine release syndrome (CRS) occurred in 13 (93%, grade 1 n=9, grade 2 n=4). None developed ≥grade 3 CRS, had CRS-related ICU admission, or received Tocilizumab. CRS was associated with modest elevations of IL-6, IFN-γand IL-10. Grade 2 neurotoxicity was observed in 3 patients and resolved spontaneously. One patient had grade 4 leucoencephalopathy presumed due to chemotherapy as well as grade 5 sepsis. Ten patients (71%) had grade 3-4 cytopenia persisting beyond day 28 or recurring afterthis. 12/14 (86%) patients achieved molecular complete or continuing complete remission at a median of 30 days post infusion (range 30-90 days, Table 2). At a median follow-up of 20.3 months, 4/14 (29%) evaluable patients remain MRD negative. 5 relapsed with CD19-disease, 1 with CD19+ disease. The median duration of EFS (based on death or morphological relapse) has not been reached, 12 month EFS = 52%, OS = 70% (Figures 1, 2 and Table 3). Conclusion: We noted excellent CAR T cell expansion and persistence in a ALL cohort treated with the fast off-rate CAT-41BBz CAR despite their lower BM disease at treatment compared to other studies. The kinetics documented for all evaluable patients showed a 5-fold greater CAR T cell expansion and 2-fold longer half-life than responders in published series utilising tisagenlecleucel in a similar ALL cohort (Mueller et al., Blood 2017). Patients had a favourable toxicity profile with no severe (grade 3-4) CRS and equivalent disease outcomes to the ELIANA study despite having similarly advanced disease (Maude et al., NEJM 2018292). These data suggest long lived CAR T cell persistence supports stand-alone therapy for ALL with durable responses. Disclosures Ghorashian: Celgene: Honoraria; novartis: Honoraria; UCLB: Patents & Royalties: UCLB. Kramer:UCLB: Patents & Royalties. Ciocarlie:Servier: Other: Financial Support. Farzaneh:Autolus Ltd: Equity Ownership, Research Funding. Pule:Autolus: Employment, Equity Ownership, Patents & Royalties. Amrolia:UCLB: Patents & Royalties.

scholarly journals A Novel Low Affinity CD19CAR Results in Durable Disease Remissions and Prolonged CAR T Cell Persistence without Severe CRS or Neurotoxicity in Patients with Paediatric ALL

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 806-806
Author(s):  
Sara Ghorashian ◽  
Anne Marijn Kramer ◽  
Sarah Jayne Albon ◽  
Gary Wright ◽  
Fernanda Castro ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Transduction Efficiency ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T ◽  
Post Infusion ◽  
Grade 3

Abstract Introduction: Published studies of CD19 CAR T cells have shown unprecedented response rates in ALL but with a 23-27% incidence of severe Cytokine Release Syndrome (CRS) and 27-50% incidence of severe neurotoxicity which may limit broader application. We developed a novel second generation CD19CAR (CAT-41BBz CAR) with a lower affinity and faster off-rate but equivalent on-rate than the FMC63-41BBz CAR (Kd 116 nM vs 0.9 nM, T1/2 10s vs 1260s) utilised in CTL019 currently under consideration by the FDA. Pre-clinical studies indicated T-cells transduced with CAT-41BBz mediate enhanced tumor clearance and show increased expansion in an NSG-NALM6 stress test model (Kramer et al., submitted). We here report interim results from a multi-centre, Phase I clinical study of autologous CAT-41BBz CAR T cells as therapy for high risk/relapsed paediatric ALL, CARPALL (NCT02443831) demonstrating efficacy with an excellent safety profile. Methods: Autologous T cells were activated with anti-CD3/CD28 beads, transduced with a SIN lentiviral vector encoding CAT-41BBz CAR and expanded for 4 days prior to magnetic bead removal and cryopreservation. Transduction efficiency was assessed using an anti-idiotype antibody. Serum levels of cytokines associated with CRS were measured using cytometric bead array. All patients received lymphodepletion with fludarabine 150 mg/m2 + cyclophosphamide 1.5g/m2 followed by a single infusion of CAR T cells at a dose of 1x106 CAR+ T cells. Patients were monitored for the presence of CAR T cells in the blood by flow cytometry and by qPCR for the 41BBz junctional region, as well as circulating B cell count monthly for 6 months and then 6 weekly to 1 year. Disease status was assessed in the bone marrow morphologically, by IgH qPCR, as well as by flow cytometric assessment of MRD at the same time-points to establish durability of responses as a stand-alone therapy. The primary end-points were incidence of grade 3-5 toxicity related to CAR T cells within 30 days and the proportion of patients achieving molecular remission. Results: We have enrolled 10 patients and treated 8 to date. Six of 8 had relapsed post myeloablative SCT. The median disease burden prior to lymphodepletion was 9% blasts (ranging from molecular CR to 74% blasts, Table 1). It was possible to generate a product meeting release criteria in all but 1 patient (90% feasibility). Median transduction efficiency was 18.1% (range 6.7 to 76.3%). All treated patients received the anticipated dose of 1x106 CAR T cells/kg. Cytokine release syndrome occurred in all patients (grade 1 n=4, grade 2 n=4), but to date none have developed ≥ grade 3 CRS, required ICU admission or therapy with Tocilizumab. CRS was associated with modest elevations of IL-6, IFN-γ and IL-10 and resolved spontaneously in all. Grade 2 neurotoxicity was observed in 3 patients and resolved spontaneously, but no severe (≥grade 3) neurotoxicity was seen. Five patients had prolonged grade 4 neutropenia lasting &gt; 30 days but this resolved in all by 2 months. Only 1 patient experienced significant infective complications in the context of pre-existing poor marrow reserve following allogeneic SCT. 6/7 (86%) evaluable patients achieved molecular remission at a median of 30 days post infusion (range 30-60 days, Table 1). One patient did not respond and died of CD19+ disease progression. At a median follow-up of 5.9 months (range 28-328 days), 4/7 evaluable patients remain in flow MRD negative remission of whom 3 show no evidence of molecular MRD at 1, 7.5 and 9 months. Two patients relapsed with CD19- disease at 3 and 4 months post infusion: 1 of these remains alive with disease at 11 months and the other died of disease progression. Reflecting our pre-clinical data with CAT-41BBz CAR, we have seen excellent CAR T cell expansion (median 65459 copies/µg DNA at 1 month, range 609 to 230112) and persistence at up to 11 months post-infusion (Figure 1). All 7 evaluable patients have ongoing CAR T cell persistence detectable by both flow and qPCR as well as ongoing B cell aplasia at last follow-up. Conclusions: These interim results with a novel low affinity CD19 CAR show similar remission rates to those reported by US studies in paediatric ALL with an improved safety profile. No severe (grade ≥3) CRS or neurotoxicity has occurred to date despite high tumour burden in 4 patients. Excellent CAR T cell expansion has been documented, as well as long duration of CAR T cell persistence and associated B cell aplasia. Disclosures Ghorashian: UCL: Patents & Royalties: UCL Business. Kramer: UCL: Patents & Royalties: UCL Business. Lucchini: Alexion: Membership on an entity's Board of Directors or advisory committees. Pule: Autolus Ltd: Employment, Equity Ownership, Research Funding; UCL: Patents & Royalties: UCL Business.

Mechanical thrombectomy using a Solitaire stent retriever in the treatment of pediatric acute ischemic stroke

2019 ◽  
Vol 23 (3) ◽  
pp. 363-368 ◽  
Author(s):  
Bing Zhou ◽  
Xiao-Chuan Wang ◽  
Jun-Yi Xiang ◽  
Ming-Zhao Zhang ◽  
Bo Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Balloon Dilation ◽  
Stent Retriever ◽  
National Institutes Of Health ◽  
Clinical Prognosis ◽  
Nihss Score ◽  
Grade 3

OBJECTIVEMechanical thrombectomy using a Solitaire stent retriever has been widely applied as a safe and effective method in adult acute ischemic stroke (AIS). However, due to the lack of data, the safety and effectiveness of mechanical thrombectomy using a Solitaire stent in pediatric AIS has not yet been verified. The purpose of this study was to explore the safety and effectiveness of mechanical thrombectomy using a Solitaire stent retriever for pediatric AIS.METHODSBetween January 2012 and December 2017, 7 cases of pediatric AIS were treated via mechanical thrombectomy using a Solitaire stent retriever. The clinical practice, imaging, and follow-up results were reviewed, and the data were summarized and analyzed.RESULTSThe ages of the 7 patients ranged from 7 to 14 years with an average age of 11.1 years. The preoperative National Institutes of Health Stroke Scale (NIHSS) scores ranged from 9 to 22 with an average of 15.4 points. A Solitaire stent retriever was used in all patients, averaging 1.7 applications of thrombectomy and combined balloon dilation in 2 cases. Grade 3 on the modified Thrombolysis In Cerebral Infarction scale of recanalization was achieved in 5 cases and grade 2b in 2 cases. Six patients improved and 1 patient died after thrombectomy. The average NIHSS score of the 6 cases was 3.67 at discharge. The average modified Rankin Scale score was 1 at the 3-month follow-up. Subarachnoid hemorrhage after thrombectomy occurred in 1 case and that patient died 3 days postoperatively.CONCLUSIONSThis study shows that mechanical thrombectomy using a Solitaire stent retriever has a high recanalization rate and excellent clinical prognosis in pediatric AIS. The safety of mechanical thrombectomy in pediatric AIS requires more clinical trials for confirmation.

scholarly journals Adenosine-induced Asystole during AVM Embolization

2021 ◽  
Author(s):  
V. Hellstern ◽  
P. Bhogal ◽  
M. Aguilar Pérez ◽  
M. Alfter ◽  
A. Kemmling ◽  
...  
Keyword(s):  
Demographic Data ◽  
Clinical Results ◽  
Endovascular Embolization ◽  
Neurological Deficits ◽  
Residual Shunt ◽  
Grade 5 ◽  
Martin Grade ◽  
Grade 3 ◽  
Brain Avms

Abstract Background Adenosine induced cardiac standstill has been used intraoperatively for both aneurysm and arteriovenous malformation (AVM) surgery and embolization. We sought to report the results of adenosine induced cardiac standstill as an adjunct to endovascular embolization of brain AVMs. Material and Methods We retrospectively identified patients in our prospectively maintained database to identify all patients since January 2007 in whom adenosine was used to induce cardiac standstill during the embolization of a brain AVM. We recorded demographic data, clinical presentation, Spetzler Martin grade, rupture status, therapeutic intervention and number of embolization sessions, angiographic and clinical results, clinical and radiological outcomes and follow-up information. Results We identified 47 patients (22 female, 47%) with average age 42 ± 17 years (range 6–77 years) who had undergone AVM embolization procedures using adjunctive circulatory standstill with adenosine. In total there were 4 Spetzler Martin grade 1 (9%), 9 grade 2 (18%), 15 grade 3 (32%), 8 grade 4 (18%), and 11 grade 5 (23%) lesions. Of the AVMs six were ruptured or had previously ruptured. The average number of embolization procedures per patient was 5.7 ± 7.6 (range 1–37) with an average of 2.6 ± 2.2 (range 1–14) embolization procedures using adenosine. Overall morbidity was 17% (n = 8/47) and mortality 2.1% (n = 1/47), with permanent morbidity seen in 10.6% (n = 5/47) postembolization. Angiographic follow-up was available for 32 patients with no residual shunt seen in 26 (81%) and residual shunts seen in 6 patients (19%). The angiographic follow-up is still pending in 14 patients. At last follow-up 93.5% of patients were mRS ≤2 (n = 43/46). Conclusion Adenosine induced cardiac standstill represents a viable treatment strategy in high flow AVMs or AV shunts that carries a low risk of mortality and permanent neurological deficits.

scholarly journals Dr. Answer AI for Prostate Cancer: Predicting Biochemical Recurrence Following Radical Prostatectomy

2021 ◽  
Vol 20 ◽  
pp. 153303382110246
Author(s):  
Jihwan Park ◽  
Mi Jung Rho ◽  
Hyong Woo Moon ◽  
Jaewon Kim ◽  
Chanjung Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Random Forest ◽  
Radical Prostatectomy ◽  
Prediction Model ◽  
Biochemical Recurrence ◽  
Clinical Decision ◽  
Outcome Variable ◽  
Tertiary Hospitals ◽  
Input Variables

Objectives: To develop a model to predict biochemical recurrence (BCR) after radical prostatectomy (RP), using artificial intelligence (AI) techniques. Patients and Methods: This study collected data from 7,128 patients with prostate cancer (PCa) who received RP at 3 tertiary hospitals. After preprocessing, we used the data of 6,755 cases to generate the BCR prediction model. There were 16 input variables with BCR as the outcome variable. We used a random forest to develop the model. Several sampling techniques were used to address class imbalances. Results: We achieved good performance using a random forest with synthetic minority oversampling technique (SMOTE) using Tomek links, edited nearest neighbors (ENN), and random oversampling: accuracy = 96.59%, recall = 95.49%, precision = 97.66%, F1 score = 96.59%, and ROC AUC = 98.83%. Conclusion: We developed a BCR prediction model for RP. The Dr. Answer AI project, which was developed based on our BCR prediction model, helps physicians and patients to make treatment decisions in the clinical follow-up process as a clinical decision support system.

scholarly journals 439 Conservative Versus Surgical Management of Complicated Diverticulitis - A Retrospective Study of Long-Term Outcomes

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
E Durity ◽  
G Elliott ◽  
T Gana
Keyword(s):  
Complicated Diverticulitis ◽  
Complication Rates ◽  
Long Term Outcomes ◽  
Female Ratio ◽  
Stoma Reversal ◽  
Group A ◽  
Grade 3 ◽  
Group B

Abstract Introduction Management of complicated diverticulitis has shifted towards a conservative approach over time. This study evaluates the feasibility and long-term outcomes of conservative management. Method We retrospectively evaluated a consecutive series of patients managed with perforated colonic diverticulitis from 2013-2017. Results Seventy-three (73) patients were included with a male to female ratio of 1:2. Thirty-one (31) underwent Hartmann’s procedure (Group A) and 42 patients were managed with antibiotics +/- radiological drainage (Group B). Mean follow-up was 64.9 months (range 3-7 years). CT Grade 3 and 4 disease was observed in 64.5% and 40.4% of Group A and Group B patients, respectively. During follow-up, 9 (21.4%) Group B patients required Hartmann’s. Group A had longer median length of stay compared to Group B (25.1 vs 9.2 days). Post-operative complications occurred in 80.6% with 40% being Clavien-Dindo grade III or higher in group A. Stoma reversal was performed in 8 patients (25.8%). Conclusions In carefully selected cases, complicated diverticulitis including CT grade 3 and 4 disease, can be managed conservatively with acceptable recurrence rates (16.7% at 30 days, 4.8% at 90 days, 19.0% at 5 years). Surgical intervention on the other hand, carries high post-operative complication rates and low stoma reversal rates.

scholarly journals Flow diverter stents in the treatment of recanalized intracranial aneurysms

2021 ◽  
pp. 159101992199050
Author(s):  
Erol Akgul ◽  
Hasan Bilen Onan ◽  
Irem Islek ◽  
Mehmet Tonge ◽  
Yavuz Durmus ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Demographic Data ◽  
Previous Treatment ◽  
Flow Diverter ◽  
Serious Adverse Events ◽  
Clinical Complications ◽  
Tertiary Hospitals ◽  
The Mean ◽  
Technical Complication

Background We assessed the safety and efficacy of flow diverter stents (FDSs) in the treatment of recanalized or residual intracranial aneurysms treated endovascularly. Materials & Methods Patients whose recanalized or residual aneurysms were treated with FDSs in five tertiary hospitals were reviewed retrospectively. The patients’ demographic data, aneurysm characteristics, types of previous treatment, and clinical complications, or serious adverse events associated with FDSs, as well as the results of neurological and angiographic follow-up assessments, were recorded. Results Eighty-six patients (37 males) with 87 aneurysms were included in this study. Eighty (91.9%) aneurysms were in the anterior and seven (8.1%) in the posterior circulation. The initial treatment methods were the primary coiling or balloon remodeling technique in 69 (79.3%) and stent-assisted coiling in 18 (20.7%) aneurysms. The endovascular procedure was successful in all patients. Complications occurred in four patients, for a total complication rate of 4.6%. A technical complication developed in one patient (1.2%). An in-stent thrombosis treated with tirofiban was seen in two cases. Late in-stent stenosis exceeding 50% was treated with balloon angioplasty in one patient. The mean length of follow-up was 21.0 months. The first angiographic follow-up (3–6 months) revealed the complete occlusion of 74 aneurysms (85.1%). While 76 aneurysms (87.4%) were occluded at the last angiographic follow-up (mean: 26.0 months), 11 aneurysms (12.6%) were still filling. Morbimortality was zero. Conclusion The drawback of endovascular treatment is aneurysmal remnants or recurrences, which is safely and durably amenable to flow diversion.

scholarly journals Conservative oxygen therapy for critically ill patients: a meta-analysis of randomized controlled trials

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiao-Li Chen ◽  
Bei-Lei Zhang ◽  
Chang Meng ◽  
Hui-Bin Huang ◽  
Bin Du
Keyword(s):  
Sensitivity Analysis ◽  
Randomized Controlled Trials ◽  
Critically Ill Patients ◽  
Oxygen Therapy ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Icu Patients ◽  
Randomized Controlled

Abstract Objective Conservative oxygen strategy is recommended in acute illness while its benefit in ICU patients remains controversial. Therefore, we sought to conduct a systematic review and meta-analysis to examine such oxygen strategies’ effect and safety in ICU patients. Methods We searched PubMed, Embase, and the Cochrane database from inception to Feb 15, 2021. Randomized controlled trials (RCTs) that compared a conservative oxygen strategy to a conventional strategy in critically ill patients were included. Results were expressed as mean difference (MD) and risk ratio (RR) with a 95% confidence interval (CI). The primary outcome was the longest follow-up mortality. Heterogeneity, sensitivity analysis, and publication bias were also investigated to test the robustness of the primary outcome. Results We included seven trials with a total of 5265 patients. In general, the conventional group had significantly higher SpO2 or PaO2 than that in the conservative group. No statistically significant differences were found in the longest follow-up mortality (RR, 1.03; 95% CI, 0.97–1.10; I2=18%; P=0.34) between the two oxygen strategies when pooling studies enrolling subjects with various degrees of hypoxemia. Further sensitivity analysis showed that ICU patients with mild-to-moderate hypoxemia (PaO2/FiO2 >100 mmHg) had significantly lower mortality (RR, 1.24; 95% CI, 1.05–1.46; I2=0%; P=0.01) when receiving conservative oxygen therapy. These findings were also confirmed in other study periods. Additional, secondary outcomes of the duration of mechanical ventilation, the length of stay in the ICU and hospital, change in sequential organ failure assessment score, and adverse events were comparable between the two strategies. Conclusions Our findings indicate that conservative oxygen therapy strategy did not improve the prognosis of the overall ICU patients. The subgroup of ICU patients with mild to moderate hypoxemia might obtain prognosis benefit from such a strategy without affecting other critical clinical results.

scholarly journals LB0001 MAVRILIMUMAB IMPROVES OUTCOMES IN PHASE 2 TRIAL IN NON-MECHANICALLY-VENTILATED PATIENTS WITH SEVERE COVID-19 PNEUMONIA AND SYSTEMIC HYPERINFLAMMATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 198.2-199
Author(s):  
L. Pupim ◽  
T. S. Wang ◽  
K. Hudock ◽  
J. Denson ◽  
N. Fourie ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Oxygen Therapy ◽  
Supplemental Oxygen ◽  
Ordinal Scale ◽  
Phase 2 ◽  
Double Blind ◽  
Gm Csf ◽  
Risk Of Death ◽  
Percentage Points ◽  
Supplemental Oxygen Therapy

Background:Granulocyte/macrophage-colony stimulating factor (GM-CSF) is a cytokine both vital to lung homeostasis and important in regulating inflammation and autoimmunity1,2,3 that has been implicated in the pathogenesis of respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.4-6 Mavrilimumab is a human anti GM-CSF receptor α monoclonal antibody capable of blocking GM-CSF signaling and downregulating the inflammatory process.Objectives:To evaluate the effect of mavrilimumab on clinical outcomes in patients hospitalized with severe COVID-19 pneumonia and systemic hyperinflammation.Methods:This on-going, global, randomized, double-blind, placebo-controlled seamless transition Phase 2/3 trial was designed to evaluate the efficacy and safety of mavrilimumab in adults hospitalized with severe COVID-19 pneumonia and hyperinflammation. The Phase 2 portion comprised two groups: Cohort 1 patients requiring supplemental oxygen therapy without mechanical ventilation (to maintain SpO2 ≥92%) and Cohort 2 patients requiring mechanical ventilation, initiated ≤48 hours before randomization. Here, we report results for Phase 2, Cohort 1: 116 patients with severe COVID- 19 pneumonia and hyperinflammation from USA, Brazil, Chile, Peru, and South Africa; randomized 1:1:1 to receive a single intravenous administration of mavrilimumab (10 or 6 mg/kg) or placebo. The primary efficacy endpoint was proportion of patients alive and free of mechanical ventilation at Day 29. Secondary endpoints included [1] time to 2-point clinical improvement (National Institute of Allergy and Infectious Diseases COVID-19 ordinal scale), [2] time to return to room air, and [3] mortality, all measured through Day 29. The prespecified evidentiary standard was a 2-sided α of 0.2 (not adjusted for multiplicity).Results:Baseline demographics were balanced among the intervention groups; patients were racially diverse (43% non-white), had a mean age of 57 years, and 49% were obese (BMI ≥ 30). All patients received the local standard of care: 96% received corticosteroids (including dexamethasone) and 29% received remdesivir. No differences in outcomes were observed between the 10 mg/kg and 6 mg/kg mavrilimumab arms. Results for these groups are presented together. Mavrilimumab recipients had a reduced requirement for mechanical ventilation and improved survival: at day 29, the proportion of patients alive and free of mechanical ventilation was 12.3 percentage points higher with mavrilimumab (86.7% of patients) than placebo (74.4% of patients) (Primary endpoint; p=0.1224). Mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death through Day 29 (Hazard Ratio (HR) = 0.35; p=0.0175). Day 29 mortality was 12.5 percentage points lower in mavrilimumab recipients (8%) compared to placebo (20.5%) (p=0.0718). Mavrilimumab recipients had a 61% reduction in the risk of death through Day 29 (HR= 0.39; p=0.0726). Adverse events occurred less frequently in mavrilimumab recipients compared to placebo, including secondary infections and thrombotic events (known complications of COVID-19). Thrombotic events occurred only in the placebo arm (5/40 [12.5%]).Conclusion:In a global, diverse population of patients with severe COVID-19 pneumonia and hyperinflammation receiving supplemental oxygen therapy, corticosteroids, and remdesivir, a single infusion of mavrilimumab reduced progression to mechanical ventilation and improved survival. Results indicate mavrilimumab, a potent inhibitor of GM-CSF signaling, may have added clinical benefit on top of the current standard therapy for COVID-19. Of potential importance is that this treatment strategy is mechanistically independent of the specific virus or viral variant.References:[1]Trapnell, Nat Rev Dis Pri, 2019[2]Wicks, Nat Rev Immunology, 2015[3]Hamilton, Exp Rev Clin Immunol, 2015[4]De Luca, Lancet Rheumatol, 2020[5]Cremer, Lancet Rheumatol, 2021[6]Zhou, Nature, 2020Disclosure of Interests:Lara Pupim Employee of: Kiniksa, Shareholder of: Kiniksa, Tisha S. Wang Consultant of: Partner Therapeutics; steering committee for Kinevant BREATHE clinical trial, Kristin Hudock: None declared, Joshua Denson: None declared, Nyda Fourie: None declared, Luis Hercilla Vasquez: None declared, Kleber Luz: None declared, Mohammad Madjid Grant/research support from: Kiniksa, Kirsten McHarry: None declared, José Francisco Saraiva: None declared, Eduardo Tobar: None declared, Teresa Zhou Employee of: Kiniksa, Shareholder of: Kiniksa, Manoj Samant Employee of: Kiniksa, Shareholder of: Kiniksa, Joseph Pirrello Employee of: Kiniksa, Shareholder of: Kiniksa, Fang Fang Employee of: Kiniksa, Shareholder of: Kiniksa, John F. Paolini Employee of: Kiniksa, Shareholder of: Kiniksa, Arian Pano Employee of: Kiniksa, Shareholder of: Kiniksa, Bruce C. Trapnell: None declared

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