Reza Shaker

Introduction: Effects of aging on the relationship of striated esophagus (StEso) motor function with pharyngeal deglutitive biomechanics has not been systematically studied. Objective: The aim of this study is to characterize the effects of aging on the correlation of deglutitive StEso with pharyngeal function. Materials and Methods: We studied 33 healthy subjects. Fifteen elderly (age: 75 ± 7 years, 8 female) and 18 nonelderly (age: 50 ± 14 years, 9 F) were evaluated using high resolution manometry/impedance. Nine elderly (73 ± 7 years, 5 F) and eight young (24 ± 3 years, 4 F) were further evaluated by digital videofluoroscopy. Results and Discussion: Duration of StEso excursion averaged 2.56 ± 0.65 s in elderly and 2.33 ± 0.41 in young. We identified four periods in StEso motor function during deglutitive excursion: (a) anterosuperior ascent without bolus/peristaltic activity, (b) nonperistaltic bolus receiving function at apogee of StEso excursion during UES opening and pharyngeal peristalsis, (c) peristaltic bolus transport as StEso descends, (d) continued peristalsis in resting position. Apart from the final period described, the periods are significantly different in the elderly compared with the young subjects ( p < 0.04). Furthermore, the interaction of striated esophageal flow dynamics and peristaltic contractile vigor showed that a significant correlation ( r = −0.71, p = 0.0009) was found when comparing the average bolus injection length to the average SECI in young subjects. This correlation was muted in the elderly and did not reach statistical significance ( r = −0.41, p = 0.13). Conclusions: Sequencing of StEso/pharyngeal deglutitive motor function is preserved in the elderly. The differences observed in early stages of spatiotemporal mapping of StEso deglutitive motor function when comparing healthy elderly to young populations may be due to age‐related suprahyoid muscle weakness since the affected periods are those associated with the active StEso ascent and descent. Like young individuals, elderly pressure signatures currently attributed to the StEso deglutitive motor activity do not represent the entirety of StEso peristalsis.

Deglutitive inhibition is caused by central inhibition of ongoing esophageal phase of swallowing during the new pharyngeal phase by short-term cessation of striated muscle peristalsis and longer-term reduction in smooth muscle peristaltic magnitude. The esophageal or oral phase of swallowing does not cause deglutitive inhibition. Deglutitive inhibition is pharyngeal phase central inhibition of the esophageal phase of swallowing.

Introduction: In March 2020, the National Center for Advancing Translational Sciences—Clinical and Translational Science Awards (CTSA) Program issued an urgent “Call to Action,” requesting CTSA hubs to accelerate clinical and translational research (C&TR) in response to the COVID-19 public health emergency. The Clinical and Translational Science Institute of Southeast Wisconsin (CTSI) quickly responded by launching a regional research initiative among its eight academic and healthcare partner institutions to nucleate teams around COVID-19 C&TR.Methods: A comprehensive search of COVID-19 funding opportunities, combined with suggestions from CTSI leadership and C&TR investigators, produced a list of 31 distinct C&TR questions that were used to nucleate investigators into teams. A survey was shared with the faculty of all eight partner institutions to solicit interest in joining the teams. Multidisciplinary team formation was based on a novel CTSI model, called the “Team Science-Guided Integrated Clinical and Research Ensemble (Ensemble).” In this model, teams are formed around an unmet patient medical need, based on the intentional recruitment of members from three domains: (1) the clinical and translational research enterprise, (2) the health care systems, and (3) the community of stakeholders. The teams were provided no funding, but received substantial CTSI research and administrative support.Results: Forty-one teams were formed, and 243 investigators participated during the first year of the initiative. Team efforts resulted in the submission of 21 grant proposals, totaling $32,528,297. Three grant proposals were funded, totaling $609,888. The research initiative generated eight publications and had a significant impact on patient health, involving a combined total of 456 research participants. The initiative led to several systemic improvements, by (1) exposing investigators to team science-guided C&TR (Ensembles), (2) increasing inter-institutional and inter-departmental collaborations, (3) creating new partnerships with community organizations, and (4) providing qualitative data on lessons learned.Conclusion: The COVID-19 regional research initiative provided a compelling model of how basic science, clinical/translational, and community researchers can be mobilized for accelerated C&TR to address a public health threat. The initiative demonstrated that the fundamentals of the novel CTSI Ensemble team concept can be leveraged to expedite the formation of highly efficient teams.

Background: Internationally adopted Chicago Classification (CC) criteria based on adult normative data have been used to diagnose children with esophageal motility disorders undergoing high‐resolution esophageal manometry (HREM). The aim of this study was to compare HREM parameters of children without dysphagia and children with dysphagia and normal findings according to CC.Methods: HREM metrics of 41 children (13.2 (9–18) years; 20 female) without dysphagia and 41 children (13.7 (8–18) years; 30 female) with dysphagia and normal diagnosis according to CC were compared. Analyzed data included resting and integrated relaxation pressures (IRP) of upper (UES) and lower (LES) esophageal sphincters, esophageal peristaltic contractile integrals, transition zone (TZ) gaps, distal latency (DL), and manometric esophageal length to height ratio (MELH). 95%ile normative cutoffs were calculated from the cohort without dysphagia.Key Results: Proximal contractile integral (PCI), UES and LES mean resting and IRP were not significantly different between the cohorts (p > 0.3). On the contrary, distal contractile integral (DCI), TZ gap and MELH were notably different with p = 0.0002, p = 0.027, and p = 0.033 respectively. According to 95%ile normative cutoffs of DCI, TZ gap and MELH, in cohort with dysphagia 27%, 15%, and 22% of patients respectively were not normal.Conclusion & Inferences: First study ever to compare HREM parameters of children without dysphagia to children with dysphagia. Considerable proportion of children with dysphagia may be underdiagnosed according to the adult criteria. This emphasizes the need for universally accepted child‐specific diagnostic protocols and norms.

Background: The functional relationship of striated esophagus (St.Eso) motor function with pharyngeal deglutitive biomechanical events has not been systematically studied. The aim of this study was to determine the spatio‐temporal characteristics of St.Eso function and its correlation with pharyngeal biomechanics and bolus transport.Methods: We studied 50 healthy volunteer subjects (age range: 21–82 years, 31 female) by digital videofluoroscopy. All subjects were studied in a seated, upright position. Thirteen of these 50 volunteers also underwent high‐resolution manometry (HRM) concurrent with fluoroscopy. We used laryngeal excursion as a surrogate for St.Eso excursion.Key Results: Median duration of St.Eso excursion was 2.35 [1.93,2.85, 5th and 95th percentile] seconds. Mean maximum extent of St.Eso excursion was 2.84 ± 0.72 cm. We identified four distinct periods in deglutitive St.Eso motor function: P1. Anterosuperior ascent without bolus or peristaltic activity, P2. Non‐peristaltic bolus receiving at the apogee of St.Eso excursion concurrent with UES opening and pharyngeal peristalsis P3. Peristaltic bolus transport as St.Eso descends and P4. Continued peristalsis in resting position.Conclusions and Inferences: 1. St.Eso motor function spans both pharyngeal and esophageal phases of swallowing for receiving and transporting the bolus, 2. Pressure signatures in HRM recordings currently attributed to St.Eso deglutitive motor activity does not represent the entirety of St.Eso peristalsis, only the part that occurs in its resting position. St.Eso peristalsis that occurs during its descent is recorded by pressure sensors initially in the pharynx. This finding needs to be considered when interpreting HRM recordings of the pharynx and proximal esophagus.

Circumferential tension of cervical esophagus (CTE) increases during esophageal peristalsis. CTE response is correlated with distal longitudinal tension on cervical esophagus during esophageal peristalsis but not laryngeal elevation or esophageal muscle contraction. CTE response is not blocked by transection of motor innervation of laryngeal elevating muscles or proximal esophagus but is temporally reduced after hexamethonium administration. We conclude that the CTE response is a biomechanical effect caused by longitudinal esophageal contraction during esophageal peristalsis.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, and more than 80% of PD patients will develop oropharyngeal dysphagia. Despite its striated histology, proximity to airway, and potential negative impact of its dysfunction on bolus transport and airway safety, the contractile function of the striated esophagus in PD patients has not been systematically studied.Methods: Using our repository of clinical manometry and the Milwaukee ManoBank, we analyzed high‐resolution manometry (HRM) studies of 20 PD patients, mean age 69.1 (range 38–87 years); 30 non‐PD patients with dysphagia, mean age 64.0 (44–86 years); and 32 healthy volunteers, mean age 65.3 (39–86 years). Patients with abnormal findings based on Chicago Classification 4.0 were identified. Repeat analysis was performed in 20% of the manometric tracings by a different investigator with inter‐rater concordance between 0.91 and 0.99.Key Results: The striated esophageal contractile integral in PD patients was significantly lower than that in non‐PD dysphagic patients and healthy controls (p = 0.03 and p = 0.02 and 0.01, respectively). In both analyses, the distal esophageal contractile integral did not show any significant difference between groups (p = 0.58 and 0.93, respectively).Conclusions & Inferences: PD is associated with a significant decrease in striated esophagus contractility compared to non‐PD and healthy controls. This finding may play a pathophysiologic role in development of dysphagia in this patient population.