Effect of Topical Nasal Anesthetic on Comfort and Swallowing in High-Resolution Impedance Manometry.

OBJECTIVES/HYPOTHESIS: Use of topical nasal anesthetic (TNA) is common in high-resolution impedance manometry (HRIM). This study investigated the effect of TNA on swallowing and procedure tolerability during HRIM with a 4.2-mm catheter, a more commonly used catheter size with impedance capabilities. STUDY DESIGN: Randomised experimental study with blinding of participants. METHODS: Twenty healthy participants (mean age = 33 years, 16 female) were randomized to undergo HRIM using the ManoScan™ ESO Z 4.2-mm catheter twice, 1 week apart, under two conditions: with TNA (viscous lidocaine) and with placebo. Analyses included esophageal data of three saliva, three saline (5 mL), and three bread swallows (2 cm × 2 cm) performed while reclined 45°, and pharyngeal data under the same conditions while seated upright. Pharyngeal and upper esophageal sphincter (UES) HRIM parameters were analyzed using the Swallow Gateway analysis platform. Visual analogue scale (VAS) scores rating procedural comfort were analyzed. RESULTS: There were no significant physiological differences in pharyngeal and UES parameters between conditions. There were also no significant differences in VAS scores under placebo (mean = 54.8, standard deviation (SD) = 19.3) and TNA (mean = 60.0, SD = 21.9) (t[19] = -0.9, P = .4) conditions; however, there was a significant difference in the first versus second session (t[19]) = 5.1, P < .05). CONCLUSIONS: TNA did not improve comfort, but it also did not significantly affect swallowing behavior. There was, however, a practice effect regardless of TNA use with improved tolerance of the 4.2-mm catheter and likely more natural swallowing behavior during the second session of HRIM. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2124-2131, 2022.

High-Resolution Pharyngeal Manometry and Impedance: Protocols and Metrics-Recommendations of a High-Resolution Pharyngeal Manometry International Working Group.

High-resolution manometry has traditionally been utilized in gastroenterology diagnostic clinical and research applications. Recently, it is also finding new and important applications in speech pathology and laryngology practices. A High-Resolution Pharyngeal Manometry International Working Group was formed as a grass roots effort to establish a consensus on methodology, protocol, and outcome metrics for high-resolution pharyngeal manometry (HRPM) with consideration of impedance as an adjunct modality. The Working Group undertook three tasks (1) survey what experts were currently doing in their clinical and/or research practice; (2) perform a review of the literature underpinning the value of particular HRPM metrics for understanding swallowing physiology and pathophysiology; and (3) establish a core outcomes set of HRPM metrics via a Delphi consensus process. Expert survey results were used to create a recommended HRPM protocol addressing system configuration, catheter insertion, and bolus administration. Ninety two articles were included in the final literature review resulting in categorization of 22 HRPM-impedance metrics into three classes: pharyngeal lumen occlusive pressures, hypopharyngeal intrabolus pressures, and upper esophageal sphincter (UES) function. A stable Delphi consensus was achieved for 8 HRPM-Impedance metrics: pharyngeal contractile integral (CI), velopharyngeal CI, hypopharyngeal CI, hypopharyngeal pressure at nadir impedance, UES integrated relaxation pressure, relaxation time, and maximum admittance. While some important unanswered questions remain, our work represents the first step in standardization of high-resolution pharyngeal manometry acquisition, measurement, and reporting. This could potentially inform future proposals for an HRPM-based classification system specifically for pharyngeal swallowing disorders.

Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses.

Clostridium difficile-associated diarrhoea (CDAD) is caused by C. difficile toxins A and B and represents a serious emerging health problem. Yet, its progression and functional consequences are unclear. We hypothesised that C. difficile can drive major measurable metabolic changes in the gut microbiota and that a relationship with the production or absence of toxins may be established. We tested this hypothesis by performing metabolic profiling on the gut microbiota of patients with C. difficile that produced (n=6) or did not produce (n=4) toxins and on non-colonised control patients (n=6), all of whom were experiencing diarrhoea. We report a statistically significant separation (P-value <0.05) among the three groups, regardless of patient characteristics, duration of the disease, antibiotic therapy and medical history. This classification is associated with differences in the production of distinct molecules with presumptive global importance in the gut environment, disease progression and inflammation. Moreover, although severe impaired metabolite production and biological deficits were associated with the carriage of C. difficile that did not produce toxins, only previously unrecognised selective features, namely, choline- and acetylputrescine-deficient gut environments, characterised the carriage of toxin-producing C. difficile. Additional results showed that the changes induced by C. difficile become marked at the highest level of the functional hierarchy, namely the metabolic activity exemplified by the gut microbial metabolome regardless of heterogeneities that commonly appear below the functional level (gut bacterial composition). We discuss possible explanations for this effect and suggest that the changes imposed by CDAD are much more defined and predictable than previously thought.

Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity.

The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to carbohydrate metabolism, and to contribute to unravel the underlying mechanisms and consequences for health conditions. We measured the activity level of GIT carbohydrate-active enzymes toward 23 distinct sugars in adults patients (n = 2) receiving 14-d ß-lactam therapy and in obese (n = 7) and lean (n = 5) adolescents. We observed that both 14 d antibiotic-treated and obese subjects showed higher and less balanced sugar anabolic capacities, with 40% carbohydrates being preferentially processed as compared with non-treated and lean patients. Metaproteome-wide metabolic reconstructions confirmed that the impaired utilization of sugars propagated throughout the pentose phosphate metabolism, which had adverse consequences for the metabolic status of the GIT microbiota. The results point to an age-independent positive association between GIT glycosidase activity and the body mass index, fasting blood glucose and insulin resistance (r ( 2) ≥ 0.95). Moreover, antibiotics altered the active fraction of enzymes controlling the thickness, composition and consistency of the mucin glycans. Our data and analyses provide biochemical insights into the effects of antibiotic usage on the dynamics of the GIT microbiota and pin-point presumptive links to obesity. The knowledge and the hypotheses generated herein lay a foundation for subsequent, systematic research that will be paramount for the design of "smart" dietary and therapeutic interventions to modulate host-microbe metabolic co-regulation in intestinal homeostasis.