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BACKGROUND : Peroral endoscopic myotomy (POEM) is now widely used for esophageal motility disorders including achalasia. Closure of the mucosal incision site is a critical step of the procedure. We evaluated the use of a novel through-the-scope (TTS) suture system for closure of POEM mucosal incision sites. METHODS : We retrospectively reviewed consecutive patients who underwent POEM with TTS suture closure at our institution between February and July 2021. Technical success was defined as complete mucosal incision site closure using TTS suturing, without the need for adjunctive devices. Continuous variables are presented as median (interquartile range [IQR]) or mean (SD). RESULTS : 35 consecutive patients (median age 58 years [IQR 46.5-72]; 54.3 % female) underwent POEM with attempted mucosal closure by TTS suturing. Technical success was achieved in 32 patients (91.4 %) with a mean closure time of 12.4 (SD 6.9) minutes. The median mucosal incision length at time of closure was 2.5 cm (IQR 2-2.5). Overall, 17 patients (53.1 %) required ≥ 2 TTS suture systems and 3 patients (8.6 %) required additional TTS clips to achieve secure mucosal closure. No adverse events were encountered. CONCLUSIONS : TTS suturing was effective and safe for POEM mucosotomy closure. However, prospective comparative trials and cost-effectiveness analyses are warranted before routine adoption.BACKGROUND : Peroral endoscopic myotomy (POEM) is now widely used for esophageal motility disorders including achalasia. Closure of the mucosal incision site is a critical step of the procedure. We evaluated the use of a novel through-the-scope (TTS) suture system for closure of POEM mucosal incision sites. METHODS : We retrospectively reviewed consecutive patients who underwent POEM with TTS suture closure at our institution between February and July 2021. Technical success was defined as complete mucosal incision site closure using TTS suturing, without the need for adjunctive devices. Continuous variables are presented as median (interquartile range [IQR]) or mean (SD). RESULTS : 35 consecutive patients (median age 58 years [IQR 46.5–72]; 54.3 % female) underwent POEM with attempted mucosal closure by TTS suturing. Technical success was achieved in 32 patients (91.4 %) with a mean closure time of 12.4 (SD 6.9) minutes. The median mucosal incision length at time of closure was 2.5 cm (IQR 2–2.5). Overall, 17 patients (53.1 %) required ≥ 2 TTS suture systems and 3 patients (8.6 %) required additional TTS clips to achieve secure mucosal closure. No adverse events were encountered. CONCLUSIONS : TTS suturing was effective and safe for POEM mucosotomy closure. However, prospective comparative trials and cost-effectiveness analyses are warranted before routine adoption.

Vaccination elicits a complex combination of immune responses. Immune memory formation is observed not only in the antibody responses of B-cells, but also in the T-cell response. Moreover, some live attenuated vaccines such as measles-containing vaccines can induces heterologous protection, likely through induction of memory characteristics in the innate immune response. Little is known about the immunological interaction that may occur when different vaccines are administered soon after one another, especially in relation to the novel COVID-19 vaccines.The aim of this study was to compare the innate and adaptive immune responses between persons randomized to receive either a MMR or a placebo (0.9% NaCl) injection prior to their SARS-CoV-2 mRNA vaccination. We compared: i) the cytokine and chemokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10, IL-17, IL-22, interferon [IFN]-α and IFN-γ) after in-vitro stimulation of peripheral blood mononuclear cells (PBMCs) with heterologous stimuli (severe acute respiratory syndrome coronavirus [SARS-CoV]-2, measles mumps and rubella [MMR] vaccine, Toll-like receptor [TLR]-3 ligand, TLR-7/8 ligand, or TLR-4 ligand), and ii) the SARS-CoV-2 neutralizing antibody responses.Ninety-five participants in the CROWN CORONATION trial (NCT04333732; a randomized control trial comparing MMR to placebo for prevention of COVID-19) agreed to an additional single blood sample collection for this immunological study. Samples were collected around 196 (SD 22) days after administration of MMR or placebo, and around 105 (SD 27) days after their second SARS-CoV-2 mRNA vaccine injection.Twenty-four percent of participants were older than fifty and sixty-seven percent were female. The median TNF-α response to stimulation with MMR was 8315.3 pg/mL in the MMR group and 4340.5 pg/mL in the placebo group; adjusted median difference (95% CI) 3012.5 (−4734.1; −323.5); p=0.017. No other significant differences were noted in the cytokine and chemokine responses between treatment groups. The SARS-CoV-2 neutralization assay geometric mean (SD) IC50 in the MMR group was 507.6 (2.6) and in the placebo group was 515.7 (2.2); ratio of geometric means (95% CI) 1.0 (0.7; 1.5).Pre-exposure to MMR vaccine was generally not associated with changes in cytokine and chemokine responses of stimulated PBMCs at 105 (27) days after SARS-CoV-2 mRNA vaccination. MMR vaccination led only to an increase of TNF-α production in response to an additional ex-vivo stimulation with the MMR vaccine. The SARS-CoV-2 neutralization IC50 values did not differ between MMR and placebo groups. Further studies using a repeated measures design would be better suited to explore or rule-out any short-lived vaccine response and vaccine-vaccine immunological interaction.

Purpose of review Gastroesophageal reflux disease (GERD) is one of the most common chronic conditions affecting adults. A substantial proportion of patients continue to have symptoms despite medical therapy, and there has been increased demand for minimally invasive GERD therapy. We will examine currently available techniques and outcomes data on endoscopic approaches to the treatment of GERD. Recent findings In the last 2 years, research has given rise to more robust understanding of not only the pathophysiology of GERD but also how to better manage the various phenotypes. We are learning the ideal patient to benefit from endoscopic GERD therapy. In this review, we describe the four major endoluminal techniques for treating GERD and summarize current data. Summary Endoscopic therapies are well positioned to fill the 'therapy gap' between medical therapy and more invasive surgical procedures.

Background and Aims Flexible endoscopic cricopharyngeal myotomy (FECM) allows minimally invasive treatment of patients with Zenker’s diverticulum (ZD); however, retreatment rates are substantial. We hypothesized that the functional lumen imaging probe (FLIP) may provide insight into ZD pathophysiology and serve as an intraprocedural guide to adequacy of myotomy. Methods We prospectively evaluated 11 ZD patients undergoing FECM and compared the baseline cricopharyngeal (CP) distensibility with 16 control subjects. Intraprocedural CP distensibility was measured immediately pre- and postmyotomy. The CP distensibility index (CP-DI) was defined as a ratio of the narrowest cross-sectional area (nCSA) and the corresponding intrabag pressure at 40 mL distension. Same-procedure myotomy extension was undertaken in a subgroup if threshold distensibility changes were not met. Results ZD patients had reduced baseline nCSA and CP-DI compared with control subjects, (169.6 vs 227.5 mm2 [P Conclusions CP distensibility is reduced in ZD patients and is partially reversible by FECM. An intraprocedural FLIP CP distensibility measurement is safe and sensitive in detecting myotomy-induced changes. These findings support using FLIP to optimize FECM outcome. Further studies are required to derive precise metrics predictive of clinical response.

Simple Summary Colorectal cancer is the third most diagnosed cancer worldwide and contributes significantly to global mortality and morbidity. The gut microbiome, composed of the trillions of microbes endemic to the human gastrointestinal tract, has been shown to be implicated in colorectal cancer oncogenesis; however, the roles of microbiota and dysbiosis in CRC treatment remain poorly understood. This review sought to characterize this relationship and in doing so, identify how these interactions may inform future treatments in the form of synbiotics designed to alter the host microbiota to achieve optimized treatment outcomes. Abstract In healthy hosts, trillions of microbes colonise the gut and oral cavity in a well-balanced state, maintaining a mutually beneficial relationship. Loss of this balance, termed dysbiosis, is strongly implicated in the pathogenesis of colorectal cancer (CRC). However, the roles of microbiota and dysbiosis in CRC treatment remain poorly understood. Recent studies suggest that the gut microbiota has the ability to affect the host response to chemotherapeutic agents by enhancing drug efficacy, promoting chemoresistance and mediating chemotherapy-induced toxicity and side effects via a variety of mechanisms. Several other studies have also proposed manipulation of the microbiota to optimise CRC treatment. In this review, we summarise the current advancement of knowledge on how microbiota and CRC treatments interact with each other and how this interaction may shed some light on the development of personalised microbiota manipulations that improve CRC treatment outcomes.

Vitamin B12-binding proteins were detected in the body fluids and/or tissues of horseshoe crabs ( Limulus polyphemus ), clams and sponges. Among the biological specimens tested the Limulus plasma was especially rich in free B12-binding proteins. Gel filtration experiments revealed that Limulus plasma contains two classes of B12-binding proteins. One class of proteins, molecular weight in excess of 100,000, bind B12 preferentially with affinity constant of 5×1011M−1. The second type of proteins, molecular weights around 50,000, bind B12 with specificity approaching that of mammalian intrinsic factors. The binding constant of these proteins for B12 is around 1011M−1.