Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial.

BACKGROUND: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. METHODS: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. RESULTS: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. CONCLUSIONS: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.

A nationwide survey of clinical use of blood in Italy.

BACKGROUND: In Italy, as in many developed countries, a decline in blood component (BC) consumption, especially red blood cells (RBC), has been described, but not studied at a national level. We, therefore, designed a nationwide survey to determine the main features of BC recipients and obtain a picture of the clinical use of BC for the first time in Italy, in order to understand BC demands better and identify specific fields in which to apply Patient Blood Management (PBM). MATERIAL AND METHODS: A nationwide survey of all Italian Blood Establishments working as Hospital Blood Banks (HBB) was performed. Data were collected through an online report form recording information on the number and geographic area of the responding HBB, year of birth and sex of the BC recipients, and clinical indications for every unit of RBC, platelets and plasma transfused in a 24-hour period. RESULTS: On the survey date, 153/237 (64.5%) of the HBB returned 4,356 forms, reporting 7,523 transfusions. The median and mean ages of the recipients were 73 (range, 0-106) and 67.5 years, respectively; 33.0% were >80 years old and 64.9% >65 years old, with no relevant differences between males and females. Overall, 6,309 RBC units were transfused to 3,850 recipients, 66.7% of them for a medical indication and 32.4% for a surgical indication. The commonest medical indication was acquired, non-cancer-related anaemia and more than 30% of the transfusions occurred in the Emergency Department. Five hundred and sixty platelet transfusions were given to 520 recipients, 62.7% of them for prophylaxis and 28.6% for bleeding before or during an invasive procedure or surgery or for thrombocytopenia. One hundred and ninety-four patients received 654 units of plasma, 71.1% of which were for therapeutic purposes in bleeding patients. DISCUSSION: We collected a picture of blood transfusion epidemiology in Italy. The data suggest that future PBM plans should be focused on medical anaemia especially in the setting of Emergency Departments.

Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19.

Passive immunotherapy with plasma derived from patients convalescent from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that Blood Establishments are prepared to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution and control of use of the product. This position paper is aimed to give recommendations on biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.

Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19.

Passive immunotherapy with plasma derived from convalescent patients recovering from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that blood establishments are ready to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution, and control of product use. This Position paper aims to give recommendations on the biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.

Transversus abdominis plane (TAP) block versus thoracic epidural analgesia (TEA) in laparoscopic colon surgery in the ERAS program.

AIM: The enhanced recovery after surgery (ERAS) pathway and laparoscopic approach had been proven beneficial for patients and should now be considered as a standard of care in colorectal surgery. Multimodal analgesia is the gold standard in the ERAS program with the use of thoracic epidural analgesia (TEA). Few data are available on Transversus abdominis plane (TAP) blocks in laparoscopic colorectal surgery and ERAS pathway. The aim of this study is to evaluate the efficacy of TAP block compared to TEA in the management of postoperative pain and the impact on the recurrence of postoperative nausea, vomiting and ileus in laparoscopic colorectal surgery in the ERAS program. METHOD: From October 2014 to October 2016, 182 patients underwent elective colon surgical interventions in enhanced recovery after surgery pathway. The patients were divided into two groups: Group 1 (n = 92) and Group 2 (n = 91) who received TEA and TAP block, respectively, with a standardized postoperative analgesic regimen consisting of regular 1 g of paracetamol every 8 h and a rescue dose with intravenous non-steroidal anti-inflammatory drugs infusion for both groups. RESULTS: No differences were observed in baseline patient characteristics, clinical variables and surgical procedures between the two groups, as well as in the postoperative complications rate (p = 0.515) in accordance with Clavien-Dindo classification, 90-day mortality (p = 0.319), hospital stay (p = 0.469) and 30-day readmission rate (p = 0.711). Patients in the TAP block group showed lower postoperative nausea and vomiting rates (p = 0.025), as well as lower ileus (p = 0.031) and paraesthesia rates (p = 0.024). No differences were found in urinary retention (p = 0.157). Despite the "opioid-free" analgesia protocol in the TAP block group, pain intensity was comparable between the two groups (p = 0.651). CONCLUSION: TAP block combined with an opioid-sparing analgesia in the setting of the laparoscopic colorectal surgery and ERAS program is feasible and effective in postoperative pain control.

E.R.A.S. pathway in colorectal surgery in elderly: Our experience: A retrospective cohort study.

AIM: Numerous geriatric patients develop colorectal disease. Elderly patients are often considered high-risk surgical candidates. Enhanced recovery after surgery (E.R.A.S.) has been proven to be beneficial for patients. The aim of the study was to evaluate the results of an ERAS protocol in older patients that underwent colorectal surgery compared to younger patients. METHOD: In the period between January 2010 to December 2015 a total of 589 patients underwent elective colorectal surgical interventions treated within the E.R.A.S pathway: 211 patients younger than 65 years, 175 patients aged from 66 years to 75 years, and 203 patients older than 75 years. End point of interest were postoperative complications, 90-day mortality, length of hospital stay and readmission within 30 days. RESULTS: Significant differences between the three groups were observed for comorbidities (p:0.001); in particular older patients had significantly more diabetes, renal, cardiac, and respiratory diseases, ASA (p < 0.001), presence of malignancy (p < 0.001). However there were not differences between the groups in surgical procedures (p = 0.095), operative time (p = 0.823), anastomotic leakage (p = 0.960), hospital stay (p = 0.081), readmission rate (p = 0.904), 90-days mortality (p = 0.183) and morbidity (p = 0.973) in accordance with Clavien-Dindo classification. Multivariate logistic regression analysis showed that advanced age in E.R.A.S. pathway is not a predictive factor of morbidity, readmission within 30 days and 90-day mortality. CONCLUSION: There was no significant difference in morbidity, 90-day mortality, length of stay or readmission rate in patients aged over 75 years compared with younger patients. Old age does not represent a contraindication to the implementation of the E.R.A.S protocol in patients that underwent colorectal surgery. WHAT DOES THIS PAPER ADD TO THE EXISTING LITERATURE?: In the literature there are not many studies that address the impact of older age in the treatment of colorectal disease in an ERAS program. The aging of the population raises new questions in the management of the colorectal surgery in the elderly. ERAS pathway has been proven to be beneficial for patients, which results in a reduction of postoperative morbidity. Compared to what is reported in the literature this study confirms that ERAS program in colorectal surgery can be applied in older patients with no significant difference in morbidity, 90-day mortality, length of stay or readmission rate compared with younger.

Laparoscopic complete mesocolic excision with central vascular ligation in 600 right total mesocolectomies: Safety, prognostic factors and oncologic outcome.

BACKGROUND: To analyze our experience with laparoscopic right Mesocolectomy in right colonic cancers. METHODS: 600 consecutive patients were studied. RESULTS: Mortality was 0.5%; morbidity was 35.5%. Mean mesocolic area was 15339 ± 1639 mm3, specimen length 24.3 ± 3.3 cm, distance from the tumor to high tie was 103 ± 6 mm and mean lymph nodes harvested was 27 ± 3; mesocolic plane was achieved in 81% of cases. Survival was 83%; stratified survival in patients with stage II, IIIA/B and in the subgroup of stage IIIC patients with negative apical nodes was 88.7%, 72.4%, 71.4% respectively; stage IIIC patients with positive apical nodes showed poor survival (27.7%). Recurrence occurred in 177 patients (29.5%) and was mainly systemic (22.7%). At the multivariate analysis, "non mesocolic" plane of resection, positive N3 apical nodes and CEA levels >5 ng/dL were found to be independent prognostic factors. CONCLUSIONS: Laparoscopic right Mesocolectomy showed to be safe and yielded surgical specimens of high quality, with impact on survival; positive N3 apical nodes and "non mesocolic" planes were independently associated to poor outcome.

"Ultra" E.R.A.S. in laparoscopic colectomy for cancer: discharge after the first flatus? A prospective, randomized trial.

BACKGROUND: Enhanced Recovery After Surgery (E.R.A.S.) programs are now widely accepted in colonic laparoscopic resections because of faster recovery and less perioperative complications. The aim of this study was to assess safety and feasibility of discharging patients operated on by laparoscopic colectomy on postoperative day 2, so long as the first flatus has passed and in the absence of complication-related symptoms. METHODS: This study was a non-inferiority, open-label, single-center, prospective, randomized study comparing "Ultra" to Classic E.R.A.S. with discharge on POD 2 and 4, respectively. Seven hundred and sixty-five patients with resectable non-metastatic colonic cancer were analyzed: 384 patients were assigned to "Ultra" E.R.A.S. and 381 to Classic E.R.A.S. Primary end-point was mortality; secondary end-points were morbidity, readmission and reoperation rate. Limitations are: it is a single-center experience; it is not double-blind, with the intrinsic risk of intentional or unconscious bias; exclusion criteria because of "non-compliance" may be considered arbitrary. RESULTS: Mortality was 0.89 % in "Ultra" E.R.A.S. group and 0.59 % in Classic E.R.A.S. (p = 0.571). Morbidity was 34.1 % for "Ultra" E.R.A.S. arm and 35.4 % for Classic E.R.A.S. (p = 0.753). Readmissions were 5.6 % for "Ultra" E.R.A.S. and 5.9 % for Classic E.R.A.S. (p = 0.359). Reoperation rate was 3.8 % for "Ultra" ERAS and 4.7 % for Classic E.R.A.S. (p = 0.713). Multivariate regression analyses using Cox's proportional hazard model showed that mortality (primary end-point), morbidity, reoperation and readmission (secondary end-points) were not significantly influenced by the two different perioperative regimens; conversely, the global cost of "Ultra" E.R.A.S. regimen was more economically effective. CONCLUSION: "Ultra" E.R.A.S. showed to be safe, actual and effective; discharge on postoperative day 2 after the first flatus passage, in the absence of complication-related symptoms, should be actively considered in a modern, multidisciplinary, multimodal laparoscopic management of colonic cancer.