Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. Methods: Open-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate. Results: Of 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion. Conclusion: Immediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration- did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.

Yield of capsule endoscopy in obscure gastrointestinal bleeding: A comparative study between premenopausal and menopausal women.

AIM: To evaluate differences in capsule endoscopy (CE) performed in the setting of obscure gastrointestinal bleeding (OGIB) among premenopausal women (PMW) and menopausal women (MW). METHODS: Retrospective, single-center study, including female patients submitted to CE in the setting of OGIB between May 2011 and December 2016. Patients were divided into 2 groups according to age, considering fertile age as ≤ 55 years and postmenopausal age as > 55 years. The diagnostic yield (DY), the rebleeding rate and the time to rebleed were evaluated and compared between groups. Rebleeding was defined as a drop of Hb > 2 g/dL or need for transfusional support or presence of melena/hematochezia. RESULTS: A hundred and eighty three female patients underwent CE for OGIB, of whom 30.6% (n = 56) were PMW and 69.4% (n = 127) were MW. The DY was 30.4% in PMW and 63.8% in MW. The most common findings were angiodysplasias in both groups (PMW: 21.4%, MW: 44.9%) (P = 0.003). In PMW, only 1.8% required therapeutic endoscopy. In 17.3% of MW, CE findings led to additional endoscopic treatment. Rebleeding at 1, 3 and 5 years in PMW was 3.6%, 10.2%, 10.2% and 22.0%, 32.3% and 34.2% in MW. Postmenopausal status was significantly associated with higher DY (P < 0.001), TY (P = 0.003), rebleeding (P = 0.031) and lower time to rebleed (P = 0.001). CONCLUSION: PMW with suspected OGIB are less likely to have significant findings in CE. In MW DY, need for endoscopic treatment and rebleeding were significantly higher while time to rebleed was lower.

Impact of the timing of capsule endoscopy in overt obscure gastrointestinal bleeding on yield and rebleeding rate - is sooner than 14 d advisable?

AIM: To evaluate the impact of the timing of capsule endoscopy (CE) in overt-obscure gastrointestinal bleeding (OGIB). METHODS: Retrospective, single-center study, including patients submitted to CE in the setting of overt-OGIB between January 2005 and August 2017. Patients were divided into 3 groups according to the timing of CE (≤ 48 h; 48 h-14 d; ≥ 14 d). The diagnostic and therapeutic yield (DY and TY), the rebleeding rate and the time to rebleed were calculated and compared between groups. The outcomes of patients in whom CE was performed before (≤ 48 h) and after 48 h (> 48 h), and before (< 14 d) and after 14 d (≥ 14 d), were also compared. RESULTS: One hundred and fifteen patients underwent CE for overt-OGIB. The DY was 80%, TY-46.1% and rebleeding rate - 32.2%. At 1 year 17.8% of the patients had rebled. 33.9% of the patients performed CE in the first 48 h, 30.4% between 48h-14d and 35.7% after 14 d. The DY was similar between the 3 groups (P = 0.37). In the ≤ 48 h group, the TY was the highest (66.7% vs 40% vs 31.7%, P = 0.005) and the rebleeding rate was the lowest (15.4% vs 34.3% vs 46.3% P = 0.007). The time to rebleed was longer in the ≤ 48 h group when compared to the > 48 h groups (P = 0.03). CONCLUSION: Performing CE within 48 h from overt-OGIB is associated to a higher TY and a lower rebleeding rate and longer time to rebleed.

Appropriateness of the study of iron deficiency anemia prior to referral for small bowel evaluation at a tertiary center.

AIM: To evaluate the adequacy of the study of iron deficiency anemia (IDA) in real life practice prior to referral to a gastroenterology department for small bowel evaluation. METHODS: All consecutive patients referred to a gastroenterology department for small bowel investigation due to iron deficiency anemia, between January 2013 and December 2015 were included. Both patients referred from general practitioners or directly from different hospital departments were selected. Relevant clinical information regarding prior anemia workup was retrospectively collected from medical records. An appropriate pre-referral study was considered the execution of esophagogastroduodenoscopy (EGD) with Helicobacter pylori (H. pylori) investigation, colonoscopy with quality standards (recent, total and with adequate preparation) and celiac disease (CD) screening (through serologic testing and/or histopathological investigation). RESULTS: A total of 77 patients (58.4% female, mean age 67.1 ± 16.7 years) were included. Most (53.2%) patients were referred from general practitioners, 41.6% from other hospital specialties and 5.2% directly from the emergency department. The mean pre-referral hemoglobin concentration was 8.8 ± 2.0 g/dL and the majority of anemias had microcytic (71.4%) and hypochromic (72.7%) characteristics. 77.9% of patients presented with an incomplete pre-referral study: EGD in 97.4%, with H. pylori investigation in 58.3%, colonoscopy with quality criteria in 63.6%, and CD screening in 24.7%. Patients with an appropriate study at the time of referral were younger (48.7 ± 17.7 vs 72.3 ± 12.3 years, P < 0.001). Small bowel evaluation was ultimately undertaken in 72.7% of patients, with a more frequent evaluation in patients with a quality colonoscopy at referral (78.6% vs 23.8%); P < 0.001 (OR = 11.7, 95%CI: 3.6-38.6). The most common diagnosis regarded as the likely cause of IDA was small bowel angioectasia (18.2%) but additional causes were also found in the upper and lower gastrointestinal tracts of near 20% of patients. Small bowel studies detected previously unknown non-small bowel findings in 7.7% of patients. CONCLUSION: The study of anemia prior to referral to gastroenterology department is unsatisfactory. Only approximately a quarter of patients presented with an appropriate study.