Phase II Study of a Multi-center Randomized Controlled Trial to Evaluate Oral Vitamin B12 Treatment for Vitamin B12 Deficiency After Total Gastrectomy in Gastric Cancer Patients.

BACKGROUND/AIM: This prospective multi-central randomized phase II trial evaluated the efficacy and safety of oral Vitamin B12 500 µg/day replacement compared with oral Vitamin B12 1,500 µg/day in patients with Vitamin B12 deficiency after total gastrectomy for gastric cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive oral Vitamin B12 500 µg/day or Vitamin B12 1,500 µg/day in a 1:1 ratio with a minimization method. The primary endpoint was the incidence of a normal serum Vitamin B12 level at three months after treatment. RESULTS: From January 2018 to December 2021, 3 institutions collaborated with the present study, and 74 patients were registered from these 3 institutions. The study was prematurely closed due to poor accrual after reaching almost 50% of its goal. Among the 74 recruited patients, 36 were allocated to the Vitamin B12 500 µg/day arm and 38 to Vitamin B12 1,500 µg/day arm. The incidences of patients with a normal Vitamin B12 level at 3 months (serum Vitamin B12 level >200 pg/ml) were 91.7% (33/36) in the Vitamin B12 500 µg/day arm and 100% (38/38) in the Vitamin B12 1,500 µg/day arm (p=0.3587). The types of clinical symptoms with Vitamin B12 deficiency that improved with Vitamin B12 treatment and the degree of improvement were also similar. CONCLUSION: Although the primary endpoint of the present study was not met, it was found that oral Vitamin B12 500 µg/day replacement is as effective and safe as oral Vitamin B12 1,500 µg/day replacement for Vitamin B12 deficiency.

Sustained Neutralizing Antibodies 6 Months Following Infection in 376 Japanese COVID-19 Survivors.

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19. Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients' characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20-32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman's correlation. Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147-224); median [range] years of age, 50 (20-78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman's correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig). Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.

Purification and characterization of a new platelet aggregation inhibitor with dissociative effect on ADP-induced platelet aggregation, from the venom of Protobothrops elegans (Sakishima-habu).

A platelet aggregation inhibitor, named snake venom platelet aggregation dissociator (SV-PAD)-1, with a dissociative reaction of ADP-induced platelet aggregation, was purified from the venom of Protobothrops elegans (Sakishima-habu) by gel-filtration employing Sephadex G-100, and ion-exchange chromatographies using DEAE-Sepharose Fast Flow, CM-Sepharose Fast Flow, and Mono S. By this procedure, about 1.5mg of purified protein was obtained from 1.0g of P. elegans venom. The purified protein showed a single protein band and the molecular weight was about 110kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. The pI of purified protein showed four-bands of 7.7, 7.8, 7.95, and 8.15. This protein strongly inhibited ADP-induced platelet aggregation in rabbit platelet-rich plasma (PRP), and its IC(50) was about 58nM. It inhibited ristocetin-induced platelet aggregation in rabbit PRP (IC(50): 100nM), but hardly blocked collagen-induced platelet aggregation. This protein promptly dissociated platelet aggregation in rabbit PRP stimulated by high-concentration ADP.