BackgroundBoth omeprazole and its S enantiomer (esomeprazole) have been available and used to treat  symptoms of gastroesophageal reflux disease (GERD) and conditions associated with excessive stomach acid secretion for more than a decade. Controversy exists over improved efficacy of S enantiomer (esomeprazole) over parent racemate (omeprazole). However, a comparison of the clinical outcomes of these products may reveal the rationale for switching from the racemate to single enantiomer. Since enantiomers of omeprazole are equipotent, we compared the outcomes of equal doses of each product to see if both actually differ in their efficacy’s or the reported superiority of S enantiomer is just a dose effect.MethodsA web search was carried out for randomized controlled trials with head-to-head comparisons of omeprazole and S-omeprazole. The data were abstracted and after calculating theodd ratios (OR) for the outcomes reported in each study, the combined overall odd ratios (OR’) were estimated. The random effect inverse variance method with omeprazole as the reference (OR” = 1) was used.ResultsOut of 1171 studies, 14 were deemed eligible. There was no significant difference in the therapeutic success between omeprazole and S-omeprazole as a part of triple therapy for the treatment of H. pylori in both intention-to-treat (OR’, 1.06; CI, 0.83, 1.36; p = 0.63) as well as per-protocol analysis (OR’, 1.07; CI, 0.84, 1.36; p = 0.57). For the treatment of gastro-oesophageal reflux disease, S-omeprazole was significantly but marginally superior to the racemate (OR’, 1.18; CI, 1.01, 1.38; p = 0.04). The two products were equipotent in all metrics used to assess intragastric pH except for the % patients maintaining a 24 h gastric pH above 4 (1.57; CI, 1.04, 2.381; p = 0.03).ConclusionThe therapeutic benefit of chiral switch of omeprazole is questionable considering the substantially greater economic burden involved.

The intracellular roles of Granzyme B (GrB) in immune-mediated cell killing have been extensively studied. Recent data also implicate GrB in extracellular pathways of inflammation, cytokine activation and autoimmunity. Targeting (GrB) provides a new pharmaceutical agent for various inflammatory disorders. Serpina3n is a mouse extracellular inhibitor of GrB. There is no apparent equivalent in humans. In this study, we used a novel applied genetics approach to engineer a new extracellular GrB serpin. A chimeric protein was generated in which the reactive center loop (RCL) of human extracellular antichymotrypsin (ACT) was replaced with that of serpina3n. This serpin contained 27 amino acid residues from the serpina3n RCL and the remaining 395 residues from human ACT. The insertion converted human ACT into a GrB-inhibitory serpin. Several critical residues were identified by scanning mutagenesis on the chimera and serpina3n. Targeted mutagenesis was conducted on wild-type human ACT by specifically substituting those critical residues, creating a novel inhibitor that contains 99.3% human ACT sequence with only three point mutations. Wild-type human ACT had a kass for GrB of 2.26 × 10(4) M(-1) s(-1), whereas the novel inhibitor binds GrB with a kass of 7.65 × 10(5) M(-1) s(-1). This new drug candidate can be developed in animal models and further tested in clinical trials to help us understand the role of GrB in numerous disorders.

Objectives: To review the current literature evaluating the performance of the Surgical Apgar Score (SAS). Background: The SAS is a simple metric calculated at the end of surgery that provides clinicians with information about a patient’s postoperative risk of morbidity and mortality. The SAS differs from other prognostic models in that it is calculated from intraoperative rather than preoperative parameters. The SAS was originally derived and validated in a general and vascular surgery population. Since its inception, it has been evaluated in many other surgical disciplines, large heterogeneous surgical populations, and various countries. Methods: A database and gray literature search was performed on March 3, 2020. Identified articles were reviewed for applicability and study quality with prespecified inclusion criteria, exclusion criteria, and quality requirements. Thirty-six observational studies are included for review. Data were systematically extracted and tabulated independently and in duplicate by two investigators with differences resolved by consensus. Results: All 36 included studies reported metrics of discrimination. When using the SAS to correctly identify postoperative morbidity, the area under the receiver operating characteristic curve or concordance-statistic ranged from 0.59 in a general orthopedic surgery population to 0.872 in an orthopedic spine surgery population. When using the SAS to identify mortality, the area under the receiver operating characteristic curve or concordance-statistic ranged from 0.63 in a combined surgical population to 0.92 in a general and vascular surgery population. Conclusions: The SAS provides a moderate and consistent degree of discrimination for postoperative morbidity and mortality across multiple surgical disciplines.

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