To supply a fuller morphological characterization of the vagal afferents innervating the lower esophageal sphincter (LES), specifically to label vagal terminals in the tissues forming the LES in the gastroesophageal junction, the present experiment employed injections of dextran biotin into the nodose ganglia of rats. Four types of vagal afferents innervated the LES. Clasp and sling muscle fibers were directly and prominently innervated by intramuscular arrays (IMAs). Individual IMA terminals subtended about 16° of arc of the esophageal circumference, and, collectively, the terminal fields were distributed within the muscle ring to establish a 360° annulus of mechanoreceptors in the sphincter wall. 3D morphometry of the terminals established that, compared to sling muscle IMAs, clasp muscle IMAs had more extensive arbors and larger receptive fields. In addition, at the cardia, local myenteric ganglia between smooth muscle sheets and striated muscle bundles were innervated by intraganglionic laminar endings (IGLEs), in a pattern similar to the innervation of the myenteric plexus throughout the stomach and esophagus. Finally, as previously described, the principle bundle of sling muscle fibers that links LES sphincter tissue to the antropyloric region of the lesser curvature was innervated by exceptionally long IMAs as well as by unique web ending specializations at the distal attachment of the bundle. Overall, the specialized varieties of densely distributed vagal afferents innervating the LES underscore the conclusion that these sensory projections are critically involved in generating LES reflexes and may be promising targets for managing esophageal dysfunctions.

Background The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. Methods Sprague Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days post-injection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal were counterstained. Key Results The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with interstitial cells of Cajal. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings (IGLEs), the two types of mechanoreceptors found throughout stomach smooth muscle. Conclusions & Inferences The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors.

Tenofovir is one of the most widely used medications for HIV treatment and is administered as either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Use of TAF is preferred as it is associated with fewer negative impacts on renal function; however, long-term follow-up beyond 96 weeks is limited. A retrospective chart review of patients ≥18 years who received TDF-containing anti-retroviral therapy (ART) for ≥6 months and then switched to a TAF-containing regimen between 1 December 2015 and 1 January 2020 is presented. The primary objective was to evaluate changes in kidney function as measured by eGFR and Scr. The secondary objective was to evaluate changes in lipids. Among the 142 patients identified, the median age was 66 years old with a median follow-up of 3.6 years. The change in kidney function was a median increase in Scr of 0.1 mg/dL and a decrease in eGFR of −8 mL/min/1.73 m2. The change in lipid panels at the end of the medication use evaluation endpoint was a decrease in total cholesterol, LDL, HDL, and triglycerides of −2.5, −0.1, −0.6, and −9 mmol/L, respectively. There was no clinically meaningful difference in kidney function as measured by eGFR or Scr, nor was there any clinically meaningful difference in lipid panels in patients switched from TDF to TAF-containing ART. Our observations suggest that the favorable impact of TAF on kidney function is sustained for at least 44 months after conversion from TDF.