Compact, ultrastable, high repetition-rate 2 µm and 3 µm fiber laser for seeding mid-IR OPCPA.

We report a compact and reliable ultrafast fiber laser system optimized for seeding a high energy, 2 µm pumped, 3 µm wavelength optical parametric chirped pulse amplification to drive soft X-ray high harmonics. The system delivers 100 MHz narrowband 2 µm pulses with >1 nJ energy, synchronized with ultra-broadband optical pulses with a ∼1 µm FWHM spectrum centered at 3 µm with 39 pJ pulse energy. The 2 µm and 3 µm pulses are derived from a single 1.5 µm fiber oscillator, fully fiber integrated with free-space downconversion for the 3 µm. The system operates hands-off with power instabilities <0.2% over extended periods of time.

Effect of monensin on milk production efficiency and milk composition in lactating dairy cows fed modern diets.

Since the US Food and Drug Administration's approval of monensin in 2004, significant nutritional advances have been made to increase feed efficiency and milk fat production. Recent evidence suggests monensin's adverse effect on milk fat percentage may be absent when diets are formulated to address known diet-induced milk fat depression risk factors. Thus, study objectives were to evaluate effects of monensin level on dry matter intake (DMI), milk production and composition, and efficiency of high-producing cows fed diets formulated to optimize milk fat. Ninety-six lactating Holstein cows (36 primiparous, 60 multiparous; 106 ± 17 d in milk [DIM]) were balanced by parity, DIM, and milk production and were randomly assigned to 1 of 12 pens with 8 cows per pen. All cows received 11 g/t monensin for 5 wk after which pens received 1 of 4 dietary treatments (n = 3) formulated to provide 0 (CON), 11 (R11), 14.5 (R14.5), or 18 (R18) g/t monensin for 9 wk. The basal diet was 54% forage, 27% NDF, 29% starch, and 2.3% rumen unsaturated fatty acid load. Pen was the experimental unit and data were analyzed using the Fit Model Procedure of JMP. Effects of treatment, time, and treatment × time interaction were included as fixed effects and pen as a random effect. Least squares means were determined and linear and quadratic contrasts were tested. Dry matter intake tended to decrease linearly with increasing monensin dose. Milk yield, fat percentage, and protein percentage and yield were unaffected by treatment while fat yield was quadratically increased. Milk de novo and mixed fatty acid (FA) yields (g/d) increased quadratically with monensin whereas preformed FA linearly decreased during the experimental period. Energy-corrected milk (ECM) was quadratically increased by monensin. Milk urea nitrogen concentrations increased linearly with increasing monensin dose. Monensin linearly increased feed efficiency (ECM/DMI, 3.5% fat-corrected milk/DMI, and solids-corrected milk/DMI). Body weight gain did not differ between treatments. Estimated dietary energy tended to increase linearly with increasing monensin level. These data suggest monensin improves component-corrected milk production efficiency, estimated dietary energy, and does not negatively affect milk fat percentage or FA profile.

Numerical investigation of gas-filled multipass cells in the enhanced dispersion regime for clean spectral broadening and pulse compression.

We show via numerical simulations that the regime of enhanced frequency chirp can be achieved in gas-filled multipass cells. Our results demonstrate that there exists a region of pulse and cell parameters for which a broad and flat spectrum with a smooth parabolic-like phase can be generated. This spectrum is compatible with clean ultrashort pulses, whose secondary structures are always below the 0.5% of its peak intensity such that the energy ratio (the energy contained within the main peak of the pulse) is above 98%. This regime makes multipass cell post-compression one of the most versatile schemes to sculpt a clean intense ultrashort optical pulse.

Nonlinear post-compression in multi-pass cells in the mid-IR region using bulk materials.

We numerically investigate the regime of nonlinear pulse compression at mid-IR wavelengths in a multi-pass cell (MPC) containing a dielectric plate. This post-compression setup allows for ionization-free spectral broadening and self-compression while mitigating self-focusing effects. We find that self-compression occurs for a wide range of MPC and pulse parameters and derive scaling rules that enable its optimization. We also reveal the solitonic dynamics of the pulse propagation in the MPC and its limitations and show that spatiotemporal/spectral couplings can be mitigated for appropriately chosen parameters. In addition, we reveal the formation of spectral features akin to quasi-phase matched degenerate four-wave mixing. Finally, we present two case studies of self-compression at 3-µm and 6-µm wavelengths using pulse parameters compatible with driving high-field physics experiments. The simulations presented in this paper set a framework for future experimental work using few-cycle pulses at mid-IR wavelengths.

Photonic crystal resonators for inverse-designed multi-dimensional optical interconnects.

We experimentally demonstrate a 400 Gbit/s optical communication link utilizing wavelength-division multiplexing and mode-division multiplexing for a total of 40 channels. This link utilizes a novel, to the best of our knowledge, 400 GHz frequency comb source based on a chip-scale photonic crystal resonator. Silicon-on-insulator photonic inverse-designed 4 × 4 mode-division multiplexer structures enable a fourfold increase in data capacity. We show less than -10 dBm of optical receiver power for error-free data transmission in 34 out of a total of 40 channels using a PRBS31 pattern.

New materials for improving catches of horseflies (Diptera: Tabanidae) in Nzi traps.

New materials in 85 configurations were tested relative to standard fabric Nzi traps to improve catches of tabanids based on artificial visual cues that mimic those used in nature for locating hosts or water. Colour-fast synthetic fabrics and photo-selective horticultural mesh were tested to facilitate insecticide impregnation and for improved durability. Many plastics were explored to document how flies react to polarized and visible vs. ultraviolet light. Lastly, sticky horizontal, linearly polarizing ground-level shiny plastic targets were tested for capturing water-seeking tabanids relative to traps and vertical fabric targets. Based on the capture of 281 786 female Tabanidae (Tabanus Linnaeus, Hybomitra Enderlein, Chrysops Meigen), four alternative formats provided higher catches and/or durability. They were substituting: (1) phthalogen turquoise for phthalogen blue, (2) solution-dyed fabrics for blue and black cotton, (3) clear/white horticultural mesh for mosquito netting, and (4) clear, reflective plastic for some or all netting. A Sunbrella/BioNet fabric trap (portable) and a blue-black Plexiglas®/netting trap (fixed applications) consistently performed best (1.5-3 × higher catches). Ground-level targets captured many male and gravid female Hybomitra but were ineffective for Tabanus. Traps and vertical fabric or transparent sticky targets captured mainly unfed females.

Liver development is restored by blastocyst complementation of HHEX knockout in mice and pigs.

BACKGROUND: There are over 17,000 patients in the US waiting to receive liver transplants, and these numbers are increasing dramatically. Significant effort is being made to obtain functional hepatocytes and liver tissue that can for therapeutic use in patients. Blastocyst complementation is a challenging, innovative technology that could fundamentally change the future of organ transplantation. It requires the knockout (KO) of genes essential for cell or organ development in early stage host embryos followed by injection of donor pluripotent stem cells (PSCs) into host blastocysts to generate chimeric offspring in which progeny of the donor cells populate the open niche to develop functional tissues and organs. METHODS: The HHEX gene is necessary for proper liver development. We engineered loss of HHEX gene expression in early mouse and pig embryos and performed intraspecies blastocyst complementation of HHEX KO embryos with eGFP-labeled PSCs in order to rescue the loss of liver development. RESULTS: Loss of HHEX gene expression resulted in embryonic lethality at day 10.5 in mice and produced characteristics of lethality at day 18 in pigs, with absence of liver tissue in both species. Analyses of mouse and pig HHEX KO fetuses confirmed significant loss of liver-specific gene and protein expression. Intraspecies blastocyst complementation restored liver formation and liver-specific proteins in both mouse and pig. Livers in complemented chimeric fetuses in both species were comprised of eGFP-labeled donor-derived cells and survived beyond the previously observed time of HHEX KO embryonic lethality. CONCLUSIONS: This work demonstrates that loss of liver development in the HHEX KO can be rescued via blastocyst complementation in both mice and pigs. This complementation strategy is the first step towards generating interspecies chimeras for the goal of producing human liver cells, tissues, and potentially complete organs for clinical transplantation.

Effects of prepartum diets varying in dietary energy density and monensin on early-lactation performance in dairy cows.

Our objectives were to evaluate the effects of prepartum monensin supplementation and dry-period nutritional strategy on the postpartum productive performance of cows fed monensin during lactation. A total of 102 Holstein cows were enrolled in the experiment (32 primiparous and 70 multiparous). The study was a completely randomized design, with randomization restricted to balance for parity, body condition score, and expected calving date. A 2 × 2 factorial arrangement of prepartum treatments was used; the variables of interest were prepartum feeding strategy [controlled-energy diet throughout the dry period (CE) vs. controlled-energy diet from dry-off to 22 d before expected parturition, followed by a moderate-energy close-up diet from d 21 before expected parturition through parturition (CU)] and prepartum monensin supplementation [0 g/t (control, CON) or 24.2 g/t (MON); Rumensin; Elanco Animal Health, Greenfield, IN]. Lactation diets before and after the dry period contained monensin at 15.4 g/t. During the close-up period, cows fed CU had greater DM and NEL intakes than cows fed CE. Calf BW at birth tended to be greater for cows fed CU than for those fed CE but was not affected by MON supplementation. Diet did not affect calving difficulty score, but cows supplemented with MON had an increased calving difficulty score. We found a tendency for a MON × parity interaction for colostral IgG concentration, such that multiparous MON cows tended to have lower IgG concentration than CON cows, but colostral IgG concentration for primiparous MON and CON cows did not differ. Postpartum milk yield did not differ between diets but tended to be greater for cows supplemented with MON. Milk fat and lactose content were greater for cows fed CU than for those fed CE, and lactose content and yield were increased for cows supplemented with MON. Solids-corrected and fat-corrected milk yields were increased by MON supplementation, but were not affected by diet. Overall means for postpartum DMI did not differ by diet or MON supplementation. The CU diet decreased the concentration of nonesterified fatty acids during the close-up period but increased it postpartum. Neither diet nor monensin affected ß-hydroxybutyrate or liver composition. Overall, postpartum productive performance differed little between prepartum dietary strategies, but cows fed MON had greater energy-corrected milk production. In herds fed monensin during lactation, monensin should also be fed during the dry period.

Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model.

Surgical site infection risk continues to increase due to lack of efficacy in current standard of care drugs. New methods to treat or prevent antibiotic-resistant bacterial infections are needed. Multivalent Adhesion Molecules (MAM) are bacterial adhesins required for virulence. We developed a bacterial adhesion inhibitor using recombinant MAM fragment bound to polymer scaffold, mimicking MAM7 display on the bacterial surface. Here, we test MAM7 inhibitor efficacy to prevent Gram-positive and Gram-negative infections. Using a rodent model of surgical infection, incision sites were infected with antibiotic-resistant bioluminescent strains of Staphylococcus aureus or Pseudomonas aeruginosa. Infections were treated with MAM7 inhibitor or control suspension. Bacterial abundance was quantified for nine days post infection. Inflammatory responses and histology were characterized using fixed tissue sections. MAM7 inhibitor treatment decreased burden of S. aureus and P. aeruginosa below detection threshold. Bacterial load of groups treated with control were significantly higher than MAM7 inhibitor-treated groups. Treatment with inhibitor reduced colonization of clinically-relevant pathogens in an in vivo model of surgical infection. Use of MAM7 inhibitor to block initial adhesion of bacteria to tissue in surgical incisions may reduce infection rates, presenting a strategy to mitigate overuse of antibiotics to prevent surgical site infections.

An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Esophageal provocation tests: Are they useful to improve diagnostic yield of high resolution manometry?

High resolution manometry (HRM) is the gold standard to diagnose esophageal motility disorders but has some limitations. The inclusion of provocative tests might enhance the diagnostic yield of HRM. These tests are easy to perform and to add to the regular manometry protocol. Multiple rapid swallows (MRS; 5 2-mL swallows) is useful to assess the contractile reserve and deglutitive inhibition. The optimal number of MRS to perform might be 3 as suggested by Mauro et al. in this issue of Neurogastroenterology & Motility. The absence of contractile reserve might be associated with gastro-esophageal reflux disease and with an increased risk of post fundoplication dysphagia. Single viscous and solid swallows might enhance the detection of esophageal motility disorders but are not significantly associated with symptom occurrence. Test meal has the advantage to represent a real-life scenario and is promising to depict significant motility findings responsible for esophageal symptoms. Post-prandial recording might also be of interest to diagnose rumination and belching disorders. The best indication of rapid drink challenge test (free drinking of 200 mL) is currently the diagnosis of esophago-gastric junction obstruction. Finally, abdominal compression might be an option to evaluate response of esophageal peristalsis in a context of outflow resistance as proposed by Brink et al. in this issue. These provocative maneuvers appear to provide a complementary role in the evaluation of esophageal motility but require prospective studies to determine the validity of the findings and whether they will lead to changes in clinical practice.

Validation of the oesophageal hypervigilance and anxiety scale for chronic oesophageal disease.

BACKGROUND: Oesophageal hypervigilance and anxiety can drive symptom experience in chronic oesophageal conditions, including gastro-oesophageal reflux disease, achalasia and functional oesophageal disorders. To date, no validated self-report measure exists to evaluate oesophageal hypervigilance and anxiety. AIMS: This study aims to develop a brief and reliable questionnaire assessing these constructs, the oesophageal hypervigilance and anxiety scale (EHAS). METHODS: Questions for the EHAS were drawn from 4 existing validated measures that assessed hypervigilance and anxiety adapted for the oesophagus. Patients who previously underwent high-resolution manometry testing at a university-based oesophageal motility clinic were retrospectively identified. Patients were included in the analysis if they completed the EHAS as well as questionnaires assessing symptom severity and health-related quality of life at the time of the high-resolution manometry. RESULTS: Nine hundred and eighty-two patients aged 18-85 completed the study. The EHAS demonstrates excellent internal consistency (α = 0.93) and split-half reliability (Guttman = 0.87). Inter-item correlations indicated multicollinearity was not achieved; thus, no items were removed from the original 15-item scale. Principal components factor analysis revealed two subscales measuring symptom-specific anxiety and symptom-specific hypervigilance. Construct validity for total and subscale scores was supported by positive correlations with symptom severity and negative correlations with health-related quality of life. CONCLUSIONS: The EHAS is a 15-item scale assessing oesophageal hypervigilance and symptom-specfic anxiety. The EHAS could be useful in evaluating the role of these constructs in several oesophageal conditions in which hypersensitivity, hypervigilance and anxiety may contribute to symptoms and impact treatment outcomes.

A triple-blind, placebo-controlled randomised trial of the ilioinguinal-transversus abdominis plane (I-TAP) nerve block for elective caesarean section.

This study investigated the efficacy of a new ilioinguinal-transversus abdominis plane block when used as a component of multimodal analgesia. We conducted a prospective, triple-blind, placebo-controlled randomised study of 100 women undergoing elective caesarean section. All women had spinal anaesthesia with hyperbaric bupivacaine, 15 µg fentanyl and 150 µg morphine, as well as 100 mg diclofenac and 1.5 g paracetamol rectally. Women were randomly allocated to receive the ilioinguinal-transversus abdominis plane block or a sham block at the end of surgery. The primary outcome was the difference in fentanyl patient-controlled analgesia dose at 24 h. Secondary outcomes included postoperative pain scores, adverse effects and maternal satisfaction. The cumulative mean (95%CI) fentanyl dose at 24 h was 71.9 (55.6-92.7) µg in the ilioinguinal-transversus abdominis group compared with 179.1 (138.5-231.4) µg in the control group (p < 0.001). Visual analogue scale pain scores averaged across time-points were 1.9 (1.5-2.3) mm vs. 5.0 (4.3-5.9) mm (p = 0.006) at rest, and 4.7 (4.1-5.5) mm vs. 11.3 (9.9-13.0) mm (p = 0.001) on movement, respectively. Post-hoc analysis showed that the ilioinguinal-transversus abdominis group was less likely to use ≥ 1000 µg fentanyl compared with the control group (2% vs. 16%; p = 0.016). There were no differences in opioid-related side-effects or maternal satisfaction with analgesia. The addition of the ilioinguinal-transversus abdominis plane block provides superior analgesia to our usual multimodal analgesic regimen.

Evaluating the reliability and construct validity of the Eckardt symptom score as a measure of achalasia severity.

BACKGROUND: Achalasia is a disease of mechanical esophageal dysfunction characterized by dysphagia, chest pain, regurgitation, and malnutrition. The Eckardt symptom score (ESS) is the gold standard self-report assessment tool. Current guidelines outline a three-step approach to patient reported outcomes measure design. Developed prior to these policies, the ESS has not undergone rigorous testing of its reliability and validity. METHODS: Adult achalasia patients retrospectively identified via a patient registry were grouped based on treatment history. Patients were grouped PREPOST (completed ESS, GERDQ, brief esophageal dysphagia questionnaire, NIH PROMIS Global Health, high resolution manometry, timed barium esophagram prior to treatment and after) and POST (completed measures only after treatment). Clinical characteristics, treatment type and date were obtained via medical record. Standardized psychometric analyses for reliability and construct validity were performed. KEY RESULTS: 107 patients identified; 83 POST and 24 PREPOST. The ESS has fair internal consistency and split-half reliability with a single factor structure. Dysphagia accounts for half the variance in ESS, while chest pain and weight loss account for 10% each. Pre-post-surgical assessment demonstrates improvements in ESS, except for weight loss. Effect sizes range from 0.24 to 2.53, with greatest change in regurgitation. Validity of the ESS is supported by modest correlations with GERDQ, HRQOL, and physiological data. CONCLUSIONS & INFERENCES: The ESS demonstrates fair reliability and validity, with a single factor structure mostly explained by dysphagia. Based on psychometric findings, weight loss and chest pain items may be decreasing ESS reliability and validity. Further assessment of the ESS under FDA guidelines is warranted.

Inter-rater agreement of novel high-resolution impedance manometry metrics: Bolus flow time and esophageal impedance integral ratio.

BACKGROUND: Novel high-resolution impedance manometry (HRIM) metrics of bolus flow time (BFT) and esophageal impedance integral (EII) ratio have demonstrated clinical utility, though the reliability of their analysis has not been assessed. We aimed to evaluate the inter-rater agreement of the BFT and EII ratio. METHODS: HRIM studies including five upright, liquid swallows from 40 adult patients were analyzed by two raters using a customized MATLAB program to generate the BFT and EII ratio. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC) for median values generated per patient and also for all 200 swallows. KEY RESULTS: The ICC (95% confidence interval, CI) for BFT was 0.873 (0.759-0.933) for median values and 0.838 (0.778-0.881) for all swallows. The ICC (95% CI) for EII ratio was 0.983 (0.968-0.991) for median values and 0.905 (0.875-0.928) for all swallows. Median values for both BFT and EII ratio were similar between the two raters (P-values .05). CONCLUSIONS AND INFERENCES: The BFT and EII ratio can be reliably calculated as supported by generally excellent inter-rater agreement. Thus, broader utilization of these measures appears feasible and would facilitate further evaluation of their clinical utility.

Jackhammer esophagus: Assessing the balance between prepeak and postpeak contractile integral.

BACKGROUND: We hypothesized that symptoms in Jackhammer esophagus (JH) are associated with an imbalance between the prepeak and postpeak phases of contraction. Thus, we developed a method to distinguish the contractile integral components of prepeak and postpeak phase contractile activity to determine the contribution of each phase and their association with dysphagia. METHODS: Patients diagnosed with JH were enrolled and compared to controls. The first five intact swallows during manometry were analyzed. A single swallow was divided into a prepeak and postpeak phase. The contractile integral of each phase and its corresponding time-controlled integral were computed. All metrics were compared between controls and JH patients subcategorized by the impaction dysphagia question (IDQ) score with cut-off of 6. KEY RESULTS: Thirty eight JH patients and 71 controls were included. Twelve JH patients had IDQ ≤ 6 and 26 with IDQ > 6. JH patients had higher contractile integral in both phases, and a higher ratio between postpeak to prepeak contractile integral independent of duration. Similarly, JH patients with an IDQ > 6 had higher contractile metrics than those with IDQ ≤ 6. There was a correlation between the IDQ score and the ratio within the postpeak to prepeak contractile integral (r = .375). CONCLUSIONS: Abnormalities in contractile integral of the postpeak phase are more significant in JH with higher dysphagia scores Although the total postpeak contractile integral was higher in symptomatic patients, this was associated with longer duration of postpeak activity suggesting that dysphagia patients with JH have a defect in the postpeak phase of peristalsis.

Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients.

BACKGROUND: Esophageal dysfunction and gastro-esophageal reflux disease (GERD) are common among patients with systemic sclerosis (SSc). Although high-dose proton pump inhibitors (PPIs) typically normalize esophageal acid exposure, the effectiveness of PPI therapy has not been systematically studied in SSc patients. The aim of this study was to characterize reflux in SSc patients on high-dose PPI using esophageal pH-impedance testing. METHODS: In this case-controlled retrospective analysis, 38 patients fulfilling 2013 American College of Rheumatology SSc criteria who underwent esophageal pH-impedance testing on twice-daily PPI between January 2014 and March 2017 at a tertiary referral center were compared with a control-cohort of 38 non-SSc patients matched for PPI formulation and dose, hiatal hernia size, age, and gender. Patient clinical characteristics, including endoscopy and high-resolution manometry findings, were assessed via chart review. KEY RESULTS: On pH-impedance, SSc patients had higher acid exposure times (AETs) than controls. Sixty-one percent of the SSc patients and 18% of the control patients had a total AET ≥4.5% (P < .001). Systemic sclerosis patients also had significantly longer AETs, longer median bolus clearance, and lower nocturnal impedance values. CONCLUSIONS & INFERENCES: Abnormal esophageal acid exposure despite high-dose PPI therapy was common among patients with SSc. The lack of increased reflux episodes in the SSc patients, and longer bolus clearance times and lower nocturnal impedance, supports ineffective clearance as the potential mechanism. Systemic sclerosis patients may require adjunctive therapies to PPIs to control acid reflux.

The relationship between esophageal acid exposure and the esophageal response to volumetric distention.

BACKGROUND: Increased esophagogastric junction (EGJ) distensibility is thought to contribute to gastroesophageal reflux disease (GERD). Using the functional lumen imaging probe (FLIP), we aimed to assess the esophageal response to distension among patients undergoing esophageal pH monitoring. METHODS: 25 patients (ages 22-73; 13 females) who underwent ambulatory wireless esophageal pH testing while off proton-pump inhibitors were evaluated with FLIP during sedated upper endoscopy. Esophageal reflux was quantified by total percent acid exposure time (AET; <6% was considered normal). FLIP studies were analyzed using a customized program generate FLIP topography plots to identify esophageal contractility patterns and to calculate the EGJ-distensibility index (DI). Reflux symptoms were assessed with the GERDQ. Values reflect median (interquartile range). RESULTS: Among all patients, the AET was 7.2% (3.7-11.1) and EGJ-DI was 4.2 (2.5-7.6) mm2 /mm Hg. Repetitive antegrade contractions (RACs) were induced in 19/25 (76%) of patients; AET was lower among patients with (6.1%, 3-7.8) than without (14.9, 8.5-22.3) RACs (P = .009). Correlation was weak and insignificant between AET and EGJ-DI, GERDQ and AET, and GERDQ and EGJ-DI. Patients with abnormal AET (n = 16) and normal AET (n = 9) had similar EGJ-DI, 4.6 mm2 /mm Hg (2.9-9.2) vs 3.2 (2.2-5.1), P = .207 and GERDQ, P = .138. CONCLUSIONS: Abnormal esophageal acid exposure was associated with an impaired contractile response to volume distention of the esophagus. This supports that acid exposure is dependent on acid clearance mechanisms.

High-resolution manometry assessment of the lower esophageal sphincter after-contraction: Normative values and clinical correlation.

BACKGROUND: The Chicago Classification v3.0 proposed extending the distal contractile integral (DCI) measurement domain to include the lower esophageal sphincter (LES) to enhance the detection of esophageal hypercontractility. However, normative and clinical data for this approach are unreported. We aimed to describe the application of an extended DCI measurement in asymptomatic controls and patients. METHODS: High-resolution manometry (HRM) of 65 asymptomatic controls and 72 patients with normal motility were evaluated retrospectively. Dysphagia and chest pain symptoms were assessed using the brief esophageal dysphagia questionnaire (BEDQ); ≥10 was considered abnormal. HRM studies of 10 supine swallows were evaluated via the standard DCI and an extended DCI measurement domain (DCI+) to include the lower esophageal sphincter (LES) during and after the peristaltic wave. The DCI-increment was calculated as the DCI+ minus DCI. KEY RESULTS: Among controls, the median (5-95th percentile) DCI+ was 1915 (1359-6921) mm Hg/cm/s and DCI-increment was 534 (126-1488) mm Hg/cm/s. Two patients (3%) had ≥2 swallows with DCI+ >8000 mm Hg/cm/s and seven (10%) patients had at least one swallow with DCI+ >8000 mm Hg/cm/s, ie, had potential motility reclassification by application of DCI+. Seven of these nine patients (78%) were evaluated for dysphagia or chest pain, but only 3/9 (33%) had an abnormal BEDQ. CONCLUSIONS AND INFERENCES: Extension of the DCI measurement domain may aid quantifying hypercontractility that involves the LES. However, adjusting management strategies based on reclassification of patients with otherwise normal motility should be cautiously considered.