scholarly journals Safety and Long-term Improvement of Mesenchymal Stromal Cell Infusion in Critically COVID-19 Patients: A Randomized Clinical Trial.

2021 ◽  
Author(s):  
Carmen Kuniyoshi Rebelatto ◽  
Alexandra Cristina Senegaglia ◽  
Claudio Luciano Franck ◽  
Debora Regina Daga ◽  
Patrícia Shigunov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Critically Ill ◽  
Adjunctive Therapy ◽  
Invasive Mechanical Ventilation ◽  
Chronic Phase ◽  
Cell Subpopulation ◽  
Regeneration Ability ◽  
Persistent Symptoms

Abstract Background: COVID-19 is a multisystem disease that presents acute and persistent symptoms, the PostAcute Sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen for by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord-MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is the first report that presents the longest follow-up after MSC treatment in COVID-19 patients. Methods: This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation – critically ill patients – were included. The patient infusion was three doses of 5x105 cells/kg UC-MSCs, with a dosing interval of 48 hours (n=11) or placebo (n=6). These evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. Results: The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer, and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in lung extension was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. Conclusions: UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration: Brazilian Registry of Clinical Trials (ReBEC), UTN code - U1111-1254-9819. Registered 31 October 2020 - Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr

scholarly journals Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 patients. A controlled clinical trial.

2021 ◽  
Author(s):  
Jose Lenin Beltran Gonzalez ◽  
Mario Gonzalez Gamez ◽  
Emmanuel Antonio Mendoza Enciso ◽  
Ramiro Josue Esparza Maldonado ◽  
Daniel Hernandez Palacios ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mechanical Ventilation ◽  
Critically Ill ◽  
Invasive Mechanical Ventilation ◽  
Controlled Clinical Trial ◽  
Treatment Groups ◽  
Intention To Treat ◽  
Duration Of Hospitalization ◽  
Group 2

Background The proportion of critically ill COVID 19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation. Methods This is a controlled, randomized, open clinical trial of patients with pneumonia secondary to SARS CoV 2 infection, that fulfilled criteria for severe or critical disease. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8 hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days. Results: One hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 to 72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 to 26). Mortality at 28 days was 45.2 % (n=86). In the intention to treat analysis, there was no difference between groups neither in mortality on follow up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti SARS CoV 2 antibodies. Conclusions: In critically ill patients or on invasive mechanical ventilation for treatment of COVID19, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients.

Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19

2021 ◽  
pp. 088506662110625
Author(s):  
Sudham Chand ◽  
Sumit Kapoor ◽  
Ali Naqvi ◽  
Jyotsana Thakkar ◽  
Melissa J. Fazzari ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hospital Discharge ◽  
Medical Center ◽  
Invasive Mechanical Ventilation ◽  
Kidney Injury ◽  
Persistent Symptoms ◽  
Increased Risk ◽  
Telephone Questionnaire

Background Little is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes. Methods We conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020). Results 126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge. Conclusion Persistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.

scholarly journals Clinical Outcomes and Independent Risk Factors for 90-day Mortality in Critically-ill Patients Infected With SARS CoV-2: a Multicenter Study in Turkish Intensive Care Units

2021 ◽  
Author(s):  
Kursat Gundogan ◽  
Ismail Hakki Akbudak ◽  
Pervin Hanci ◽  
Burcin Halacli ◽  
Sahin Temel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Critically Ill ◽  
Fluid Balance ◽  
Critically Ill Patients ◽  
Lactate Level ◽  
Invasive Mechanical Ventilation ◽  
Positive Fluid Balance

Abstract Background: There are limited data on long-term outcome and mortality predictors of COVID-19 from different parts of the world. The aim of this study was to determine risk factors of 90-day mortality in critically-ill patients infected with SARS-CoV-2 in Turkish ICUs. Methods: This multicenter, retrospective study was performed in 26 ICUs in Turkey. All patients with confirmed SARS-CoV2 infection, requiring more than 24 hours of ICU follow-up were included in the study. Demographics, clinical characteristics, laboratory variables, respiratory support, treatment types, and survival data were recorded. Results: A total of 421 patients were included in the study. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. 90-day mortality rate was 55.1%. Factors independently associated with 90-day mortality were receiving invasive mechanical ventilation (HR 4.09 [95% CI: 2.20-7.63]), admission lactate level > 2 mmol/L (2.78 [1.93-4.01]), age ≥ 60 years (2.45 [1.48-4.06)]), having cardiac arrhythmia during ICU stay (2.01 [1.27-3.20]), receiving vasopressor treatment (1.94 [1.32-2.84]), positive fluid balance of ≥ 600 ml/per day during ICU follow-up (1.68 [1.21-2.34]), admission PaO2/FiO2 ratio of ≤ 150 mmHg (1.66 [1.18-2.32], and baseline ECOG score ≥ 1 (1.42 [1.00-2.02]. Conclusion: This study has shown that long-term mortality was high in critically-ill COVID-19 patients in Turkish ICUs. Invasive mechanical ventilation, high lactate level, older age, presence of cardiac arrhythmia, need for vasopressor treatment, positive fluid balance, severe hypoxemia and not having fully-active performance were related with mortality.

Nivolumab in advanced esophageal squamous cell carcinoma (ATTRACTION-1/ONO-4538-07): Minimum of five-year follow-up.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Kato ◽  
Yuichiro Doki ◽  
Takashi Ura ◽  
Yasuo Hamamoto ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Group Performance ◽  
Objective Response

207 Background:ATTRACTION-1/ONO-4538-07 (AT-1), an open-label, single-arm, multicenter phase 2 clinical trial conducted in Japan, evaluated the clinical activity and safety of nivolumab in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory/intolerant to fluoropyrimidine-, platinum-, and taxane-based chemotherapy. We previously reported the 2-year follow-up findings of AT-1, in which nivolumab demonstrated antitumor activity with a manageable safety profile for these patients. Here we report the final findings from AT-1 at a minimum follow-up of 5 years. Methods:Patients aged ≥20 years with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 received 3 mg/kg nivolumab intravenously every 2 weeks in 6-week cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally-assessed objective response rate (ORR), defined as the proportion of patients whose best overall response was either a complete or partial response. Secondary endpoints included overall survival (OS), investigator-assessed ORR, progression-free survival (PFS), change in tumor burden, time to response, time to disease progression, and duration of response. Results:Between February 25 and November 14, 2014, a total of 65 patients were enrolled. Sixty-four patients were evaluated for the efficacy, and all patients were evaluated for the safety. At the final database lock on August 6, 2020, 11 (17.2%, 95% confidence interval [CI] 9.9-28.2) of 64 patients had an objective response by central assessment. The median OS was 10.8 months (95% CI, 7.4-13.9), and the estimated 5-year OS rate was 6.3% (95% CI, 2.0-14.0). The median PFS was 1.5 months (95% CI, 1.4-2.8), and the estimated 5-year PFS rate was 6.8% (95% CI, 2.2-15.1). Treatment-related adverse events that occurred with a frequency of > 10% were diarrhea and rash. The presentation will include characteristics of long-term survivors as well as detailed efficacy and safety data of nivolumab. Conclusions:This final assessment represents the longest follow-up of patients with advanced ESCC treated with nivolumab. Nivolumab demonstrated continued long-term efficacy in these patients based on a minimum of 5-year long-term survival update of AT-1. Furthermore, no new safety signals with nivolumab were identified during long-term follow-up. These findings are consistent with those of nivolumab monotherapy for various types of cancer. Clinical trial information: No.142422.

Sign in / Sign up

Export Citation Format

Share Document