Remimazolam for sedation in gastrointestinal endoscopy:A comprehensive review

Worldwide,a majority of routine endoscopic procedures are performed under some form of sedation to maximize patient comfort.Propofol,benzodiazepines and opioids continue to be widely used.However,in recent years,Remimazolam is gaining immense popularity for procedural sedation in gastrointestinal(GI)endoscopy.It is an ultra-short-acting benzodiazepine sedative which was approved by the Food and Drug Administration in July 2020 for use in procedural sedation.Remimazolam has shown a favorable pharmacokinetic and pharmacodynamic profile in terms of its non-specific metabolism by tissue esterase,volume of distribution,total body clearance,and negligible drug-drug interactions.It also has satisfactory efficacy and has achieved high rates of successful sedation in GI endoscopy.Furthermore,studies have demonstrated that the efficacy of Remimazolam is non-inferior to Propofol,which is currently a gold standard for procedural sedation in most parts of the world.However,the use of Propofol is associated with hemodynamic instability and respiratory depression.In contrast,Remimazolam has lower incidence of these adverse effects intra-procedurally and hence,may provide a safer alternative to Propofol in procedural sedation.In this comprehensive narrative review,highlight the pharmacologic characteristics,efficacy,and safety of Remimazolam for procedural sedation.We also discuss the potential of Remimazolam as a suitable alternative and how it can shape the future of procedural sedation in gastroenterology.

PTEN inhibition and axon regeneration and neural repair

The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog （PTEN） appears critical to con- trol the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in con- ditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Im- portantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

Efficacy of peroral endoscopic myotomy vs other achalasia treatments in improving esophageal function

AIM: To assess and compare the esophageal function after peroral endoscopic myotomy(POEM) vs other conventional treatments in achalasia.METHODS: Chart review of all achalasia patients who underwent POEM, laparoscopic Heller myotomy(LHM) or pneumatic dilation(PD) at our institution between January 2012 and March 2015 was performed. Patient demographics, type of achalasia, prior treatments, pre- and post-treatment timed barium swallow(TBE) and high-resolution esophageal manometry(HREM) findings were compared between the three treatment groups. Patients who had both pre- and 2 mo posttreatment TBE or HREM were included in the final analysis. TBE parameters compared were barium column height, width and volume of barium remaining at 1 and 5 min. HREM parameters compared were basal lower esophageal sphincter(LES) pressures and LES-integrated relaxation pressures(IRP). Data are presented as mean ± SD, median [25th, 75 th percentiles] or frequency(percent). Analysis of variance, KruskalWallis test, Pearsons χ~2 test and Fishers Exact tests were used for analysis.RESULTS: A total of 200 achalasia patients were included of which 36 underwent POEM, 22 underwent PD and 142 underwent LHM. POEM patients were older(55.4 ± 16.8 years vs 46.5 ± 15.7 years, P = 0.013) and had higher BMI than LHM(29.1 ± 5.9 kg/m^2 vs 26 ± 5.1 kg/m^2, P = 0.012). More number of patients in POEM and PD groups had undergone prior treatments compared to LHM group(72.2% vs 68.2% vs 44.3% respectively, P = 0.003). At 2 mo post-treatment, all TBE parameters including barium column height, width and volume remaining at 1 and 5 min improved significantly in all three treatment groups(P = 0.01 to P < 0.001) except the column height at 1 min in PD group(P = 0.11). At 2 mo post-treatment, there was significant improvement in basal LES pressure and LES-IRP in both LHM(40.5 mm Hg vs 14.5 mm Hg and 24 mm Hg vs 7.1 mm Hg respectively, P < 0.001) and POEM groups(38.7 mm Hg vs 11.4 mm Hg and 23.6 mm Hg vs 6.6 mm Hg respectively, P < 0.001). However, when the efficacy of three treatments were compared to each other in terms of improvement in TBE or HREM parameters at 2 mo, there was no significant difference(P > 0.05).CONCLUSION: POEM, PD and LHM were all effective in improving esophageal function in achalasia at shortterm. There was no difference in efficacy between the three treatments.

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases:A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.

Text Encryption Using Pell Sequence and Elliptic Curves with Provable Security

The demand for data security schemes has increased with the significant advancement in the field of computation and communication networks.We propose a novel three-step text encryption scheme that has provable security against computation attacks such as key attack and statistical attack.The proposed scheme is based on the Pell sequence and elliptic curves,where at the first step the plain text is diffused to get a meaningless plain text by applying a cyclic shift on the symbol set.In the second step,we hide the elements of the diffused plain text from the attackers.For this purpose,we use the Pell sequence,a weight function,and a binary sequence to encode each element of the diffused plain text into real numbers.The encoded diffused plain text is then confused by generating permutations over elliptic curves in the third step.We show that the proposed scheme has provable security against key sensitivity attack and statistical attacks.Furthermore,the proposed scheme is secure against key spacing attack,ciphertext only attack,and known-plaintext attack.Compared to some of the existing text encryption schemes,the proposed scheme is highly secure against modern cryptanalysis.

Efficient construction of a substitution box based on a Mordell elliptic curve over a finite field

Elliptic curve cryptography has been used in many security systems due to its small key size and high security compared with other cryptosystems. In many well-known security systems, a substitution box (S-box) is the only non-linear component. Recently, it has been shown that the security of a cryptosystem can be improved using dynamic S-boxes instead of a static S-box. This necessitates the construction of new secure S-boxes. We propose an efficient method to generate S-boxes that are based on a class of Mordell elliptic curves over prime fields and achieved by defining different total orders. The proposed scheme is devel-oped in such a way that for each input it outputs an S-box in linear time and constant space. Due to this property, our method takes less time and space than the existing S-box construction methods over elliptic curves. Computational results show that the pro-posed method is capable of generating cryptographically strong S-boxes with security comparable to some of the existing S-boxes constructed via different mathematical structures.