Crural Diaphragm Research Articles

Role of the Kölliker-Fuse/parabrachial complex in the generation of postinspiratory vagal and sympathetic nerve activities and their recruitment by hypoxemic stimuli in the rat.

In the rat, the activity of laryngeal adductor muscles, the crural diaphragm, and sympathetic vasomotor neurons is entrained to the postinspiratory (post-I) phase of the respiratory cycle, a mechanism thought to enhance cardiorespiratory efficiency. The identity of the central neurons responsible for transmitting respiratory activity to these outputs remains unresolved. Here we explore the contribution of the Kölliker-Fuse/parabrachial nuclei (KF-PBN) in the generation of post-I activity in vagal and sympathetic outputs under steady-state conditions and during acute hypoxemia, a condition that potently recruits post-I activity. In artificially ventilated, vagotomized, and urethane-anesthetized rats, bilateral KF-PBN inhibition by microinjection of the GABAA receptor agonist isoguvacine evoked stereotypical responses on respiratory pattern, characterized by a reduction in phrenic nerve burst amplitude, a modest lengthening of inspiratory time, and an increase in breath-to-breath variability, while post-I vagal nerve activity was abolished and post-I sympathetic nerve activity diminished. During acute hypoxemia, KF-PBN inhibition attenuated tachypneic responses and completely abolished post-I vagal activity while preserving respiratory-sympathetic coupling. Furthermore, KF-PBN inhibition disrupted the decline in respiratory frequency that normally follows resumption of oxygenation. These findings suggest that the KF-PBN is a critical hub for the distribution of post-I activities to vagal and sympathetic outputs and is an important contributor to the dynamic adjustments to respiratory patterns that occur in response to acute hypoxia. Although KF-PBN appears essential for post-I vagal activity, it only partially contributes to post-I sympathetic nerve activity, suggesting the contribution of multiple neural pathways to respiratory-sympathetic coupling.NEW & NOTEWORTHY Inhibition of neurons in the pontine Kölliker-Fuse/parabrachial complex (KF-PBN) differentially inhibited postinspiratory (post-I) activity in vagal and sympathetic outputs. The strong recruitment of post-I vagal activity that occurs in response to hypoxemia is selectively abolished by KF-PBN inhibition. This suggests that 1) post-I activity in vagal and sympathetic outputs may be generated by partially independent mechanisms and 2) neurons in the KF-PBN are a preeminent source of drive for the generation of eupneic post-I activity.

Effect of hiatal hernia and esophagogastric junction morphology on esophageal motility: Evidence from high-resolution manometry studies.

High-resolution Manometry (HRM) is the most sensitive and specific test available for clinical assessment of hiatal hernia (HH), a common condition defined as the separation between the Lower Esophageal Sphincter (LES) and crural diaphragm (CD). While the link between HH and Gastroesophageal Reflux Disease (GERD) is established, the potential association of HH with esophageal dysmotility, independently from GERD, is uncertain. This study aimed to analyze if HH, with or without GERD, can associate with esophageal motility disorders. Consecutive patients without previous esophageal surgery who underwent HRM between 2018 and 2022 were enrolled. All patients with symptoms suggestive of GERD underwent impedance-pH testing off-therapy. HH was defined as a separation >1 cm between LES and CD, and esophagogastric junction (EGJ) morphology was classified as: Type I, when there was no separation between LES and CD; Type II, in case of minimal separation (>1 and <3 cm); Type III, when ≥3 cm of separation was present. Demographic and clinical characteristics were collected at baseline, including Age, Gender, Alcohol-, Coffee- and Smoke-habits, GERD diagnosis and symptoms' duration. Two cohorts of patients, with and without HH, were retrospectively individuated, and their association with Ineffective Peristalsis, Hypercontractile Esophagus and Outflow Obstruction was analyzed with univariate and multivariate Logistic regressions using the statistical software R. 848 consecutive patients were enrolled, and 295 cases of HH (34.8%), subdivided into 199 (23.5%) Type II- and 96 (11.3%) Type III-EGJ patients, were identified. Ineffective peristalsis was diagnosed in 162 (19.1%) subjects, Hypercontractile esophagus in 32 (3.8%), and Outflow Obstruction in 91 (10.7%), while GERD was present in 375 (44.2%) patients. HH was significantly associated with Ineffective Peristalsis (p < 0.001) and GERD (p < 0.001). Furthermore, HH resulted to be a risk factor for Ineffective peristalsis (OR 2.0, 95% CI 1.4-2.8, p < 0.001) both when the analysis was conducted in all the 848 subjects, independently from GERD, and when it was carried out in patients without GERD (OR 2.3, 95% CI 1.02-5.3, p = 0.04). The risk for Ineffective Peristalsis increased 1.3 times for every centimeter of HH. No statistically significant association was found between HH and Outflow obstruction or Hypercontractile Esophagus. An increasing separation between the LES and CD may lead to a gradual and significant elevation in the risk of Ineffective Peristalsis. Interestingly, this association with HH is true in patients with and in those without GERD, suggesting that the anatomical alteration seems to play a major role in motility change.

Phrenic Ampulla Emptying Dysfunction in Patients with Esophageal Symptoms.

Pharyngeal pump, esophageal peristalsis, and phrenic ampulla emptying play important roles in the propulsion of bolus from the mouth to the stomach. There is limited information available on the mechanism of normal and abnormal phrenic ampulla emptying. The goal of our study is to describe the relationship between bolus flow and esophageal pressure profiles during the phrenic ampulla emptying in normal subjects and patient with phrenic ampulla dysfunction. Pressure (using topography) and bolus flow (using changes in impedance) relationship through the esophagus and phrenic ampulla were determined in 15 normal subjects and 15 patients with retrograde escape of bolus from the phrenic ampulla into esophagus during primary peristalsis. During the phrenic ampulla phase, 2 high pressure peaks (proximal, related to lower esophageal sphincter and distal, related to crural diaphragm) were observed in normal subjects and patients during the phrenic ampulla emptying phase. The proximal was always higher than the distal one in normal subjects; in contrast, reverse was the case in patients with the retrograde escape of bolus from the phrenic ampulla into the esophagus. We propose that a strong after-contraction of the lower esophageal sphincter plays an important role in the normal phrenic ampullary emptying. A defective lower esophageal after-contraction, along with high crural diaphragm pressure are responsible for the phrenic ampulla emptying dysfunction.

Effects of aging on diaphragm hyperemia and blood flow distribution in male and female Fischer 344 rats.

Aging is associated with inspiratory muscle dysfunction; however, the impact of aging on diaphragm blood flow (BF) regulation, and whether sex differences exist, is unknown. We tested the hypotheses in young animals that diaphragm BF and vascular conductance (VC) would be greater in females and that aging would decrease the diaphragm's ability to increase BF with contractions. Young (4-6 mo) and old (22-24 mo) Fischer 344 rats were divided into four groups: young female (YF, n = 7), young male (YM, n = 8), old female (OF, n = 9), and old male (OM, n = 9). Diaphragm BF (mL/min/100 g) and VC (mL/mmHg/min/100 g) were determined, via fluorescent microspheres, at rest and during 1 Hz contractions. In YF versus OF, aging blunted the increase in medial costal diaphragm BF (44 ± 5% vs. 16 ± 12%; P < 0.05) and VC (43 ± 7% vs. 21 ± 12%; P < 0.05). Similarly, in YM versus OM, aging blunted the increase in medial costal diaphragm BF (43 ± 6% vs. 24 ± 12%; P < 0.05) and VC (50 ± 6% vs. 34 ± 10%; P < 0.05). In female rats, age increased dorsal costal diaphragm BF, whereas in male rats, age increased crural diaphragm BF(P < 0.05). Compared with age-matched females, dorsal costal diaphragm BF was lower in YM and OM (P < 0.05). In conclusion, aging results in an inability to augment medial costal diaphragm BF and alters regional diaphragm BF distribution in response to muscular contractions. Furthermore, sex differences in regional diaphragm BF are present in young and old animals.NEW & NOTEWORTHY This is the first study, to our knowledge, to demonstrate that old age impairs the hyperemic response and alters blood flow distribution in the diaphragm of both female and male rats. In addition, this investigation provides novel evidence of sex differences in regional diaphragm blood flow distribution with contractions. The data presented herein suggest that aging compromises diaphragm vascular function and provides a potential mechanism for the diaphragm contractile dysfunction associated with old age.

Pathophysiology of gastro-oesophageal reflux disease: implications for diagnosis and management.

Gastro-oesophageal reflux disease (GERD) is a common gastrointestinal disorder in which retrograde flow of gastric content into the oesophagus causes uncomfortable symptoms and/or complications. It has a multifactorial and partially understood pathophysiology. GERD starts in the stomach, where the refluxate material is produced. Following the trajectory of reflux, the failure of the antireflux barrier, primarily the lower oesophageal sphincter and the crural diaphragm, enables the refluxate to reach the oesophageal lumen, triggering oesophageal or extra-oesophageal symptoms. Reflux clearance mechanisms such as primary and secondary peristalsis and the arrival of bicarbonate-rich saliva are critical to prevent mucosal damage. Alterations of the oesophageal mucosal integrity, such as macroscopic oesophagitis or microscopic changes, determine the perception of symptoms. The intensity of the symptoms is affected by peripheral and central neural and psychological mechanisms. In this Review, we describe an updated understanding of the complex and multifactorial pathophysiology of GERD. It is now recognized that different GERD phenotypes have different degrees of reflux, severity of mucosal integrity damage and type, and severity of symptoms. These variations are probably due to the occurrence of a predominant pathophysiological mechanism in each patient. We also describe the main pathophysiological mechanisms of GERD and their implications for personalized diagnosis and management.

Divergent expiratory braking activity of costal and crural diaphragm

BackgroundThere is increasing clinical interest in understanding the contribution of the diaphragm in early expiration, especially during mechanical ventilation. However, current experimental evidence is limited, so essential activity of the diaphragm during expiration and diaphragm segmental differences in expiratory activity, are unknown. ObjectivesTo determine if: 1) the diaphragm is normally active into expiration during spontaneous breathing and hypercapnic ventilation, 2) expiratory diaphragmatic activity is distributed equally among the segments of the diaphragm, costal and crural. MethodsIn 30 spontaneously breathing male and female canines, awake without confounding anesthetic, we measured directly both inspiratory and expiratory electrical activity (EMG), and corresponding mechanical shortening, of costal and crural diaphragm, during room air and hypercapnia. ResultsDuring eupnea, costal and crural diaphragm are active into expiration, showing significant and distinct expiratory activity, with crural expiratory activity greater than costal, for both magnitude and duration. This diaphragm segmental difference diverged further during progressive hypercapnic ventilation: crural expiratory activity progressively increased, while costal expiratory activity disappeared. ConclusionThe diaphragm is not passive during expiration. During spontaneous breathing, expiratory activity -“braking”- of the diaphragm is expressed routinely, but is not equally distributed. Crural muscle “braking” is greater than costal muscle in magnitude and duration.With increasing ventilation during hypercapnia, expiratory activity -“braking”- diverges notably. Crural expiratory activity greatly increases, while costal expiratory “braking” decreases in magnitude and duration, and disappears.Thus, diaphragm expiratory "braking" action represents an inherent, physiological function of the diaphragm, distinct for each segment, expressing differing neural activation.

Selective dysfunction of the crural diaphragm in patients with chronic restrictive and obstructive lung disease.

Gastroesophageal reflux (GER) is known to be associated with chronic lung diseases. The driving force of GER is the transdiaphragmatic pressure (Pdi) generated mainly by costal and crural diaphragm contraction. The latter also enhances the esophagogastric junction (EGJ) pressure to guard against GER. The relationship between Pdi and EGJ pressure was determined using high resolution esophageal manometry in patients with interstitial lung disease (ILD, n = 26), obstructive lung disease (OLD, n- = 24), and healthy subjects (n = 20). The patient groups did not differ with respect to age, gender, BMI, and pulmonary rehabilitation history. Patients with ILD had significantly higher Pdi but lower EGJ pressures as compared to controls and OLD patients (p < 0.001). In control subjects, the increase in EGJ pressure at all-time points during inspiration was greater than Pdi. In contrast, the EGJ pressure during inspiration was less than Pdi in 14 patients with ILD and 7 patients with OLD. The drop in EGJ pressure was usually seen after the peak Pdi in ILD group (p < 0.0001) and before the peak Pdi in OLD group, (p = 0.08). Nine patients in the ILD group had sliding hiatus hernia, compared to none in control subjects (p = 0.003) and two patients in the OLD, (p = 0.04). A higher Pdi and low EGJ pressure, and dissociation between Pdi and EGJ pressure temporal relationship suggests selective dysfunction of the crural diaphragm in patients with chronic lung diseases and may explain the higher prevalence of GERD in ILD as seen in previous studies.

Impaired sliding between the lower esophageal sphincter and crural diaphragm (esophageal hiatus) in patients with achalasia esophagus.

Swallow-related axial shortening of the esophagus results in the formation of phrenic ampulla in normal subjects; whether it is the case in achalasia esophagus is not known. The goal is to study axial shortening of the esophagus and relative movement between the lower esophageal sphincter (LES) and crural diaphragm (CD) in normal subjects and patients with achalasia. A novel method, isoimpedance contour excursion at the lower edger of LES, as a marker of axial esophageal shortening was validated using X-ray fluoroscopy (n = 5) and used to study axial shortening and separation between the LES and CD during peristalsis in normal subjects (n = 15) and patients with achalasia type 2 esophagus (n = 15). Abdominal CT scan images were used to determine the nature of tissue in the esophageal hiatus of control (n = 15) and achalasia patients (n = 15). Swallow-induced peristalsis resulted in an axial excursion of isoimpedance contours, which was quantitatively similar to the metal clip anchored to the LES on X-ray fluoroscopy (2.3 ± 1.4 vs. 2.1 ± 1.4 cm with deep inspiration and 2.7 ± 0.6 cm vs. 2.7 ± 0.6 cm with swallow-induced peristalsis). Esophageal axial shortening with swallows in patients with achalasia was significantly smaller than normal (1.64 ± 0.5 cm vs. 3.59 ± 0.4 cm, P < 0.001). Gray-level matrix analysis of CT images suggests more "fibrous" and less fat in the hiatus of patients with achalasia. Lack of sliding between the LES and CD explains the low prevalence of hiatus hernia, and low compliance of the LES in achalasia esophagus, which likely plays a role in the pathogenesis of achalasia.NEW & NOTEWORTHY Swallow-related axial shortening of the esophagus is reduced, and there is no separation between the lower esophageal sphincter and crural diaphragm (CD) with swallowing in patients with achalasia esophagus. Fat in the hiatal opening of the esophagus appears to be replaced with fibrous tissue in patients with achalasia, resulting in tight anchoring between the LES and CD. The above findings explain low prevalence of hiatus hernia and the low compliance of the LES in achalasia esophagus.

The effects of age on dyspnea and respiratory mechanical and neural responses to exercise in healthy men.

The respiratory muscle pressure generation and inspiratory and expiratory neuromuscular recruitment patterns in younger and older men were compared during exercise, alongside descriptors of dyspnea. Healthy younger (n = 8, 28 ± 5 years) and older (n = 8, 68 ± 4 years) men completed a maximal incremental cycling test. Esophageal, gastric (Pga ) and transdiaphragmatic pressures, and electromyography (EMG) of the crural diaphragm were measured using a micro-transducer and EMG catheter. EMG of the parasternal intercostals, sternocleidomastoids, and rectus abdominis were measured using skin surface electrodes. After the exercise test, participants completed a questionnaire to evaluate descriptors of dyspnea. Pga at end-expiration, Pga expiratory tidal swings, and the gastric pressure-time product (PTPga ) at absolute and relative minute ventilation were higher (p < 0.05) for older compared to younger men. There were no differences in EMG responses between older and younger men. Younger men were more likely to report shallow breathing (p = 0.005) than older men. Our findings showed younger and older men had similar respiratory neuromuscular activation patterns and reported different dyspnea descriptors, and that older men had greater expiratory muscle pressure generation during exercise. Greater expiratory muscle pressures in older men may be due to compensatory mechanisms designed to offset increasing airway resistance due to aging. These results may have implications for exercise-induced expiratory muscle fatigue in older men.

Pressure dynamics of the esophagogastric junction at rest and during inspiratory maneuvers after Nissen fundoplication.

Low sphincter pressure and inability of the crural diaphragm to elevate it at the esophagogastric junction are important pathophysiological mechanisms of gastroesophageal reflux disease (GERD). The object of this study was to depict how Nissen fundoplication changed the resting and inspiratory pressures of the anti-reflux barrier. We selected 14 patients (eight males; mean age 42.7years; mean body mass index 27.8) for surgery. They answered symptoms questionnaires and underwent high-resolution manometry (HRM) before and 6months after Nissen fundoplication. We used a standard manometric protocol (resting and liquid swallows) and assessment of esophagogastric junction (EGJ) pressure metrics during standardized forced inspiratory maneuvers against increasing loads (Threshold Maneuvers). We used the Wilcoxon test for comparison of pre and postoperative data. After fundoplication, heartburn and regurgitation scores diminished remarkably (from 4.5 and 2, respectively, to zero; P = 0.002 and P = 0.0005, respective medians). Also, the median expiratory EGJ pressure had a significant increase from 8.1 to 18.1mmHg (P = 0.002), while mean respiratory pressure and EGJ contractility integral (EGJ-CI) increased without statistical significance (P = 0.064 and P = 0.06, respectively). Axial EGJ displacement was lower after fundoplication. The EGJ relaxation pressure (P = 0.001), the mean distal esophageal intrabolus pressure (P = 0.01) and the distal latency (P = 0.017) increased after fundoplication. There was a reduction in the contraction front velocity (P = 0.043). During evaluation with standardized inspiratory maneuvers, the inspiratory EGJ pressures (under loads of 12, 24, 36 and 48 cmH2O) were lower after surgery for all loads (median for load 12 cmH2O: 145.6 vs. 102.7mmHg; P = 0.004). Fundoplication and hiatal closure increased the expiratory EGJ pressure and promoted a great GERD symptom relief. The surgery seemed to overcompensate a reduced EGJ mobility and inspiratory pressure.

Intermittent Hiatus Hernia on High-Resolution Manometry Associates With Abnormal Reflux Burden Similar to Persistent Hiatus Hernia.

Hiatus hernia is characterized by axial separation between the lower esophageal sphincter and the crural diaphragm, and higher reflux burden. Impact on reflux is unclear if such separation is intermittent rather than persistent. Reflux burden off antisecretory therapy was compared between no hernia (n = 357), intermittent hernia (n = 42), and persistent hernia (n = 155) after review of consecutive high-resolution manometry and reflux monitoring studies. Proportions with pathologic acid exposure was similar between intermittent and persistent hernia (45.2% vs 46.5%, respectively), and both were significantly different from no hernia (28.7%, P ≤ 0.002). Intermittent hiatus hernias are clinically relevant in gastroesophageal reflux pathophysiology.

Is systematic formal crural repair mandatory at the time of magnetic sphincter augmentation implantation?

Laparoscopic placement of the LINX Magnetic Sphincter Augmentation (MSA) device has become an accepted alternative to fundoplication in appropriate patients. Initial studies of MSA targeted to patients with 'early' disease allowed for the most minimal dissection of the esophagus to place the device, without hiatal dissection or repair (NoHHR), in patients with no or minimal hernia findings at surgery. Subsequent studies have compared systematic formal hiatal dissection and repair (Formal HHR) with the original minimal dissection technique. Review of published literature on MSA includes discussion on treatment of hiatal hernia at the time of implantation, accompanying the review of the physiology of the crural diaphragm. Formal hiatal hernia repair at the time of MSA implantation results in better control of reflux with less dysphagia and risk of postoperative hernia than NoHHR, regardless of the presence or size of hiatal hernia. Systematic crural repair should accompany any MSA implantation regardless of the presence or size of hiatal hernia.

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden in Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility.

Background/AimsStraight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients.MethodsConsecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR.ResultsOf 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P = 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006).ConclusionOur work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

S2271 Dysphagia Aortica: An Achalasia Mimic and Pitfalls in Esophageal Manometry Interpretation

Introduction: Dysphagia aortica is a rare clinical entity wherein compression of the esophagus is due to aneurysmal dilatation of the aorta, resulting in dysphagia symptoms. Approximately 70 cases of dysphagia aortica have been reported in literature; 9 of these have been in the US. Clinical attributes of dysphagia aortica include older age, spinal abnormalities, and hypertension. Case Description/Methods: This is an 82-year-old female with relevant history of prior ascending aortic aneurysm repair with known 54 mm thoracoabdominal aortic aneurysm (TAAA), mild to moderate dysphasia, hiatal hernia and GERD presented with a food impaction. EGD was performed for food bolus retrieval and revealed a tortuous esophagus with abnormal motility/spasticity in the middle and lower esophagus. Esophageal manometry revealed a median IRP of 12.2 and 60% ineffective swallows but was limited by the inability to advance the probe beyond 43 cm. The diagnosis of achalasia was made, and the patient underwent 3 botulinum toxin injections over the next year, but without significant relief of dysphagia. A repeat CT showed interval enlargement of TAAA to 60 mm at level of diaphragmatic hiatus which compressed the distal esophagus. Discussion: Dysphagia aortica is mostly attributed to aortic aneurysm, tortuosity or dissection. Symptoms include dysphagia, cough, sternal pain and weight loss. Clinicians must be aware that LES pressure may not be reliably differentiated from other contributors to intraluminal pressure such as crural diaphragm or TAAA. Therefore, a high index of suspicion must be maintained for dysphagia aortica when interpreting manometry based on patients’ clinical attributes and comorbidities. In contrast to previously reported literature, a localized high-pressure zone was not initially noted on manometry in our patient and subsequent CT imaging demonstrated extrinsic compression – adding to the subtle variations by which dysphagia aortica may represent a diagnostic conundrum.

The American Foregut Society White Paper on the Endoscopic Classification of Esophagogastric Junction Integrity

Background: The American Foregut Society (AFS) is dedicated to advancing patient care and digestive health within the realm of foregut disease. One of the most common and debilitating esophageal conditions is gastroesophageal reflux disease (GERD). The Hill grade is an endoscopic classification of the esophagogastric junction (EGJ) based on the appearance of the gastroesophageal flap valve from a retroflexed view of the hiatus. This endoscopic classification provides insight into the anatomic disruption of the EGJ which has been shown to correlate with GERD. However, clinical utilization of this classification by endoscopists has been limited due to the perceived relevance and subjectivity of the classification. With the advent of endoscopic treatment options for GERD, there is renewed enthusiasm to develop a grading system of the EGJ that can objectively define anatomical impairment and reduce interobserver grading variability. Methods: The AFS convened a 13-member working group tasked with reviewing the Hill grade classification and formulating a proposal for its revision utilizing a modified Delphi method. This white paper summarizes the output from this working group. Results: The working group concluded that all components of the antireflux barrier—the lower esophageal sphincter and its sling fibers, the crural diaphragm, and the gastroesophageal flap valve—contribute to EGJ integrity. Using defined objective parameters of extent of hiatal axial herniation and crural disruption and presence or absence of a flap valve, the new AFS classification stratifies EGJ integrity from normal (grade 1) to increasing degrees of EGJ disruption (grade 2-4) beginning with loss of the flap valve and progressing to increasing degrees of crural disruption and hiatus hernia. This AFS classification also stipulates appropriate endoscopic methodology to utilize in making the assessment and provides a basic nomenclature for communication among endoscopists. Conclusions: The AFS endoscopic classification of the EGJ expands on the Hill classification by including assessment of axial hiatal hernia length (L), hiatal aperture diameter (D), and presence or absence of the flap valve (F) making it more comprehensive - LDF components. Future directions include validation studies correlating the ability of the AFS classification in predicting the presence and severity of GERD.

Identifying hiatal hernia with impedance planimetry during esophageal distension testing.

Functional luminal imaging probe (FLIP) Panometry evaluates the esophageal response to distension involving biomechanics and motility. We have observed that hiatus hernia (HH) is evident during FLIP studies as a separation between the crural diaphragm (CD) and lower esophageal sphincter (LES) like what is seen with high-resolution manometry (HRM). The aim of this study was to compare FLIP findings to endoscopy and HRM in the detection of HH. A total of 100 consecutive patients that completed FLIP during sedated endoscopy and HRM were included. LES-CD separation was assessed on FLIP and HRM with the presence of HH defined as LES-CD ≥1cm. The agreement was evaluated using the kappa (κ) statistic. Hiatal hernia was detected in 32% of patients on HRM and 44% of patients on FLIP with a substantial agreement between studies (84% agreement; κ= 0.667). On FLIP, a 'new' HH (i.e. HH not observed on HRM) occurred in 14 patients and an "enlarged" HH (i.e., LES-CD ≥2cm larger than on HRM) occurred in 11 patients. Among patients that also completed, timed barium esophagogram (TBE), delayed esophageal emptying on TBE was more common in patients with new or enlarged HH on FLIP than those without: 7/11 (64%) versus 2/12 (17%); p= 0.017. FLIP can detect HH with a substantial agreement with HRM, though esophageal distension with FLIP testing appeared to elicit and/or enlarge a HH in an additional 25% of patients. Although this unique response to esophageal distension may represent a mechanism of dysphagia or susceptibility to reflux, additional study is needed to clarify its significance.

Effect of Increased Intra-abdominal Pressure on the Esophagogastric Junction: A Systematic Review.

With the advent of high-resolution esophageal manometry, it is recognized that the antireflux barrier receives a contribution from both the lower esophageal sphincter (intrinsic sphincter) and the muscle of the crural diaphragm (extrinsic sphincter). Further, an increased intra-abdominal pressure is a major force responsible for an adaptive response of a competent sphincter or the disruption of the esophagogastric junction resulting in gastroesophageal reflux, especially in the presence of a hiatal hernia. This review describes how the pressure dynamics in the lower esophageal sphincter were discovered and measured over time and how this has influenced the development of antireflux surgery.

Laryngeal and swallow dysregulation following acute cervical spinal cord injury.

Laryngeal function is vital to airway protection. Although swallow is mediated by the brainstem, the mechanism underlying the increased risk of dysphagia after cervical spinal cord injury (SCI) is unknown. We hypothesized that: 1) loss of descending phrenic drive affects swallow and breathing differently, and 2) loss of ascending spinal afferent information alters swallow regulation. We recorded electromyograms (EMGs) from upper airway and chest wall muscles in freely breathing pentobarbital-anesthetized cats and rats. Laryngeal abductor activity during inspiration increased about twofold following C2 lateral hemisection. Ipsilateral to the injury, the crural diaphragm EMG amplitude was reduced during breathing (62 ± 25% change postinjury), but no animal had complete termination of activity; 75% of animals had increased contralateral diaphragm recruitment, but this did not reach significance. During swallow, laryngeal adductor and pharyngeal constrictor muscles increased activity, and diaphragm activity was bilaterally suppressed. This was unexpected because of the ipsilateral-specific response during breathing. Swallow-breathing coordination was disrupted by injury, and more swallows occurred during early expiration. Finally, to determine if the chest wall is a major source of feedback for laryngeal regulation, we performed T1 total transections in rats. As in the C2 lateral hemisection, inspiratory laryngeal recruitment was the first feature noted after injury. In contrast to the C2 lateral hemisection, diaphragmatic drive increased after T1 transection. Overall, we found that SCI alters laryngeal drive during swallow and breathing, and alters swallow-related diaphragm activity. Our results show behavior-specific effects, suggesting that swallow is affected more than breathing is by SCI, and emphasizing the need for additional studies on the effect of ascending afferents from the spinal cord on laryngeal function.NEW & NOTEWORTHY This is the first manuscript to determine the impact of cSCI on laryngeal and swallow function, and to describe a possible mechanism for dysphagia and altered airway protection after injury.

State of evidence and future perspectives in minimally invasive management of gastroesophageal reflux disease (GERD)

The future of minimally invasive treatment of gastroesophageal reflux disease (GERD) will be realized through collaborative precision medicine more than any foreseeable new technology. Multidisciplinary foregut societies are fostering the collaboration and expertise needed to provide a personalized treatment of GERD. Patient-centric therapy will consider combination therapies’ clinical successes. Taking a patient uncontrolled on medication to controlled via a combination of medicine and a procedure will replace the historical mutual exclusivity of acid-suppressive medication or surgery as a treatment for GERD. Research directed at precision medicine will focus on subgroup analysis rather than randomized controlled trials. Recognition of the crural diaphragm as a reflux barrier which fails in GERD patients regardless of the presence of an axial hernia has resulted from modalities such as 3-D high-resolution impedance manometry, endoscopic ultrasound, functional luminal impedance planimetry. More precise patient selection for purely endoscopic therapies will be possible.The concept of hernia reduction will be replaced by calibration of the crural repair to restore its sphincteric function. Partnering a surgically calibrated hernia repair partnered with interventional gastrointestinal endoscopic reinforcement of the lower esophageal sphincter will foster physician alliances and offer patient-centric alternatives to traditional fundoplication. As such, laparoscopic Nissen Fundoplication will lose its historical primacy and be relegated to the most severe GERD. Magnetic sphincter augmentation (LINX®), varing degrees of partial fundoplication, and endoluminal therapies with or without hiatal hernia repair will become the mainstay of GERD AntiReflux Procedures. Radio Frequency modulation (Stretta®) may be an alternative to neuromodulators in treating the acid-sensitive esophagus. The nascent era of endoscopic robotics will improve precision, reproducibility and revive natural orifice transluminal endoscopic surgery.

Effect of end-inspiratory lung volume and breathing pattern on neural activation of the diaphragm and extra-diaphragmatic inspiratory muscles in healthy adults.

This study examined the effect of changes in end-inspiratory lung volume (EILV) and breathing pattern on neural activation of the crural diaphragm (EMGDIA) and of the sternocleidomastoid (EMGSCM), scalene (EMGSCA), and external intercostal muscles (EMGINT) at constant ventilation (V̇E). Twelve healthy adults performed a series of 30-s breathing trials at a constant V̇E corresponding to 15% of their maximum voluntary ventilation while 1) altering EILV at a constant breathing pattern and 2) altering breathing pattern at a constant EILV. Using a real-time visual display of each participant's spirogram, EILV was voluntarily targeted at 65% (EILV65%), 75% (EILV75%), 85% (EILV85%), and 95% (EILV95%) of each participant's inspired vital capacity, whereas breathing frequency (fR) was targeted at 15, 35, and 50 breaths/min using a metronome. The tidal volume needed for a participant to maintain V̇E constant across trials was achieved via changes in end-expiratory lung volume. A multipair esophageal electrode catheter was used to record EMGDIA, whereas surface electrodes were used to record EMGSCM, EMGSCA, and EMGINT. On average, EMGDIA, EMGSCM, EMGSCA, and EMGINT increased as a function of increasing EILV at constant V̇E, independent of changes in breathing pattern. The magnitudes of these increases were particularly notable in the transition from EILV85% to EILV95%, especially for EMGSCM and EMGSCA. In healthy adults, as EILV increases toward total lung capacity, progressive compensatory increases in neural activation of the diaphragm and extra-diaphragmatic inspiratory muscles are needed to support V̇E, independent of changes in breathing pattern.NEW & NOTEWORTHY We examined the effect of changes in end-inspiratory lung volume (EILV) and breathing pattern on neural activation of the inspiratory muscles in healthy adults. We found that, at a constant ventilation, neural activation of the crural diaphragm and of the extra-diaphragmatic inspiratory muscles (sternocleidomastoid, scalene, and seventh external intercostals) increased as a function of increasing EILV, independent of changes in breathing pattern. Our results point to a critical mechanistic role of EILV in determining the level of central inspiratory neural drive needed to support ventilation.