pHoenix score: development and validation of a novel approach to decrease the number of inconclusive GERD diagnoses.

BACKGROUND: The Johnson-DeMeester composite score (DMS) is the historical gold standard for diagnosing gastroesophageal reflux disease (GERD). The Lyon Consensus outlines criteria for diagnosing GERD by pH monitoring, defining normal acid exposure time (AET) as < 4% and pathological as > 6%, presenting diagnostic uncertainty from 4 to 6%. We aimed to (i) calculate the proportion of borderline studies defined by total AET alone that are reclassified as normal or pathological by the DMS, (ii) determine the importance of supine AET for reclassification, and (iii) propose a new classification system using a composite score that considers positional changes. METHODS: This single-center, retrospective, observational study analyzed data from patients with an overall total AET from 2 to 6% on 48-h pH monitoring (Bravo pH capsule). Preselected predictors (supine and upright AET) were included in a model to create a composite score (i.e., pHoenix score) using the regression coefficients. The model was internally validated, and discriminative ability was tested against the DMS and compared to the total AET. RESULTS: We identified 114 patients (80 [70.2%] women; median age, 55 years). Using the total AET, 26 (22.8%) were classified as normal and 88 (77.2%) as borderline; however, using the DMS, 45 (39.5%) were classified as normal and 69 (60.5%) as pathological. The new pHoenix score demonstrated strong discriminative ability (AUC: 0.957 [95% CI 0.917, 0.998]) with high sensitivity and specificity (lower threshold, 94.4% and 79.2%; upper threshold, 87 and 95.8%). Compared to the total AET alone, the pHoenix score significantly decreased the proportion of inconclusive cases (77.2% vs. 13.2%, p < 0.001). CONCLUSION: Total AET has low sensitivity to identify pathological reflux as it disregards supine versus upright reflux. The pHoenix score improves the distinction between normal and pathological cases and reduces ambiguity, offering an alternative approach to diagnosing GERD that addresses the limitations of using total AET alone or the DMS.

Noninvasive biomarkers for the detection of GERD-induced pulmonary injury.

BACKGROUND: The role of gastroesophageal reflux in progressive lung damage is increasingly recognized. We have proposed, based on our work with lung transplant recipients, a novel immune mechanism of pulmonary injury after aspiration of gastric contents, during which higher levels of normally sequestered lung self-antigens (SAgs) collagen V (Col-V) and K-alpha-1 tubulin (Kα1T) in circulating small extracellular vesicles (EVs) induce the production of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. Thus, we aimed to determine whether levels of SAbs or SAgs increased in an animal model of aspiration-induced lung damage in a nontransplant setting. METHODS: We created a murine model of repetitive lung aspiration using C57BL/6J mice. Mice were aspirated weekly with 1 mL/kg of hydrochloric acid (n = 9), human gastric contents (n = 9), or combined (1:1) fluid (n = 9) once, three, or six times (n = 3 in each subgroup; control group, n = 9). Blood samples were periodically obtained, and all animals were sacrificed at day 90 for pathological assessment. SAbs were measured using an enzyme-linked immunosorbent assay; SAgs and NF-κB contained in small EVs were assessed by western blot. RESULTS: Aspirated mice weighed significantly less than controls throughout the study and had histological evidence of pulmonary injury at day 90. Overall, aspirated mice developed higher concentrations of anti-Col-V at day 28 (53.9 ± 28.7 vs. 29.9 ± 4.5 ng/mL, p < 0.01), day 35 (42.6 ± 19.8 vs. 28.6 ± 7.2 ng/mL, p = 0.038), and day 90 (59.7 ± 27.7 vs. 34.1 ± 3.2 ng/mL, p = 0.014) than the control group. Circulating small EVs isolated from aspirated mice on day 90 contained higher levels of Col-V (0.7 ± 0.56 vs. 0.18 ± 0.6 m.o.d., p = 0.009) and NF-κB (0.42 ± 0.27 vs. 0.27 ± 0.09 m.o.d., p = 0.095) than those from controls. CONCLUSIONS: This experimental study supports the theory that gastroesophageal reflux leads to the development of lung damage and an increase of humoral markers that may serve as noninvasive biomarkers to detect asymptomatic lung injury among patients with gastroesophageal reflux disease.

Collagen-V and K-α-1 Tubulin Antibodies as Potential Markers of Unsuspected GERD-Related Lung Damage: Insights from a Cross-Sectional Analysis.

PURPOSE: Our group has proposed that aspiration of gastric contents leads to exposure of normally sequestered lung self-antigens (SAgs), specifically collagen-V (Col-V) and K-α-1-tubulin (Kα1T), which elicits an immune response characterized by increasing concentrations of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. We sought to establish the point prevalence of abnormally elevated concentrations of SAbs among patients with pathological gastroesophageal reflux disease (GERD) and/or hiatal hernia undergoing antireflux surgery (ARS). METHODS: For this cross-sectional study, we retrieved a plasma aliquot from the Norton Thoracic Institute BioBank from blood samples that were taken preoperatively from patients who underwent ARS between November 2019 and August 2022. Enzyme-linked immunosorbent assays were employed to detect and quantify anti-Col-V and anti-Kα1T. RESULTS: Samples from 43 patients (females, n = 34 [79.1%]; mean age, 62 ± 12 years; and mean BMI, 30.5 ± 7  kg/m2) were analyzed. Before ARS, 28 (65.1%, CI95: 50.3-80.0%) patients had abnormally elevated concentrations of anti-Col-V and 19 (44.2%, CI95: 28.7-59.7%) had elevated concentrations of circulating anti-Kα1T. Overall, 13 patients (30.2%) had low (i.e., normal) concentrations of both SAbs, 13 (30.2%) were positive only for one, and 17 (39.5%) were positive for both SAbs. CONCLUSION: A relative high point prevalence of abnormally elevated circulating SAbs (i.e., anti-Col-V and/or anti-Kα1T) before ARS was found. This result suggests clinically unsuspected pulmonary parenchymal injury secondary to GERD-related aspiration. Further studies are required to confirm this hypothesis and to identify alternative non-invasive early biomarkers of GERD-related lung damage.

Impaired esophagogastric junction relaxation and lung transplantation outcomes.

The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)-free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan-Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.

Downregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection.

BACKGROUND: We recently demonstrated decreased tumor suppressor gene liver kinase B1 (LKB1) level in lung transplant recipients diagnosed with bronchiolitis obliterans syndrome. STE20-related adaptor alpha (STRADα) functions as a pseudokinase that binds and regulates LKB1 activity. METHODS: A murine model of chronic lung allograft rejection in which a single lung from a B6D2F1 mouse was orthotopically transplanted into a DBA/2J mouse was employed. We examined the effect of LKB1 knockdown using CRISPR-CAS9 in vitro culture system. RESULTS: Significant downregulation of LKB1 and STRADα expression was found in donor lung compared to recipient lung. STRADα knockdown significantly inhibited LKB1, pAMPK expression but induced phosphorylated mammalian target of rapamycin (mTOR), fibronectin, and Collagen-I, expression in BEAS-2B cells. LKB1 overexpression decreased fibronectin, Collagen-I, and phosphorylated mTOR expression in A549 cells. CONCLUSIONS: We demonstrated that downregulation of LKB1-STRADα pathway accompanied with increased fibrosis, results in development of chronic rejection following murine lung transplantation.

Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes severe acute respiratory syndrome. mRNA vaccines directed at the SARS-CoV-2 spike protein resulted in development of Abs and protective immunity. To determine the mechanism, we analyzed the kinetics of induction of circulating exosomes with SARS-CoV-2 spike protein and Ab following vaccination of healthy individuals. Results demonstrated induction of circulating exosomes expressing spike protein on day 14 after vaccination followed by Abs 14 d after the second dose. Exosomes with spike protein, Abs to SARS-CoV-2 spike, and T cells secreting IFN-γ and TNF-α increased following the booster dose. Transmission electron microscopy of exosomes also demonstrated spike protein Ags on their surface. Exosomes with spike protein and Abs decreased in parallel after four months. These results demonstrate an important role of circulating exosomes with spike protein for effective immunization following mRNA-based vaccination. This is further documented by induction of humoral and cellular immune responses in mice immunized with exosomes carrying spike protein.

Morbidity of antireflux surgery in lung transplant and matched nontransplant cohorts is comparable.

BACKGROUND: Safety data on perioperative outcomes of laparoscopic antireflux surgery (LARS) after lung transplantation (LT) are lacking. We compared the 30-day readmission rate and short-term morbidity after LARS between LT recipients and matched nontransplant (NT) controls. METHODS: Adult patients who underwent LARS between January 1, 2015, and October 31, 2021, were included. The participants were divided into two groups: LT recipients and NT controls. First, we compared 30-day readmission rates after LARS between the LT and NT cohorts. Next, we compared 30-day morbidity after LARS between the LT cohort and a 1-to-2 propensity score-matched NT cohort. RESULTS: A total of 1328 patients (55 LT recipients and 1273 NT controls) were included. The post-LARS 30-day readmission rate was higher in LT recipients than in the overall NT controls (14.5% vs. 2.8%, p < 0.001). Compared to matched NT controls, LT recipients had a lower prevalence of paraesophageal hernia, a smaller median hernia size, and higher peristaltic vigor. Also compared to the matched NT controls, the LT recipients had a lower median operative time but a longer median length of hospital stay. The proportion of patients with a post-LARS event within 30 postoperative days was comparable between the LT and matched NT cohorts (21.8% vs 14.5%, p = 0.24). CONCLUSIONS: Despite a higher perceived risk of comorbidity burden, LT recipients and matched NT controls had similar rates of post-LARS 30-day morbidity at our large-volume center with expertise in transplant and foregut surgery. LARS after LT is safe.

Diagnosis and management of anastomotic leaks after Ivor Lewis esophagectomy: a single-center experience.

PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center. METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed. RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality. CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.

Novel role for tumor suppressor gene, liver kinase B1, in epithelial-mesenchymal transition leading to chronic lung allograft dysfunction.

Epithelial-mesenchymal transition (EMT) has been implicated to play a role in chronic lung allograft dysfunction (CLAD). Liver kinase B1 (LKB1), a tumor suppressor gene, can regulate EMT. However, its role in CLAD development following lung transplantation remains unknown. Using qRT-PCR, biopsies from lung transplant recipients with bronchiolitis obliterans syndrome (BOS) demonstrated significant downregulation of LKB1 (p = .0001), compared to stable biopsies. To determine the role of LKB1 in EMT development, we analyzed EMT in human bronchial epithelial cell line BEAS-2B. Knockdown of LKB1 by siRNA significantly dysregulated mesenchymal markers expression in BEAS-2B cells. Following incubation of human primary bronchial epithelial cell or BEAS-2B cells with exosomes isolated from BOS or stable lung transplant recipients, LKB1 expression was inhibited when incubated with BOS-exosome. Incubation with BOS-exosomes also decreased LKB1 expression and induced EMT markers in air-liquid interface culture method. Our results provide novel evidence that exosomes released from transplanted lungs undergoing chronic rejection are associated with inactivated tumor suppressor gene LKB1 and this loss induces EMT leading to the pathogenesis of CLAD following human lung transplantation.

Outcomes after lung transplantation in recipients aged 70 years or older.

BACKGROUND: The proportion of lung transplant (LTx) recipients older than 70 years is increasing, thus we assessed long-term survival after LTx in this cohort relative to younger counterparts. PATIENTS AND METHODS: We retrospectively reviewed charts of patients who underwent LTx between 2012 and 2016 at our center and divided patients by age: group A (<65 years), B (65-69 years), and C (≥70 years). Survival statistics were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: The study included 375 LTx recipients: 221 (58.9%) in group A, 109 (29.1%) in group B, and 45 (12.0%) in group C. Group C was mostly men (37/45 [82.2%]; P = 0.003) and had the highest mean serum creatinine at listing (P = 0.02). Survival at 1, 3, and 5 years after transplant in group A (93.2%, 70.1%, 58.8%) was significantly higher than group B (83.5%, 59.6%, 44.0%; P = 0.005, 0.028, 0.006, log-rank test) and was similar to group C (86.7%, 64.4%, 57.8%), although trended higher at 1 year (P = 0.139, 0.274, 0.489, log-rank test). Groups B and C had comparable survival at all time points. CONCLUSIONS: Although survival decreased after age 65, long-term survival was comparable between LTx recipients aged 65-69 years and recipients ≥70 years.

Association of Bolus Transit Time on Barium Esophagram With Esophageal Peristalsis on High-resolution Manometry and Nonobstructive Dysphagia.

GOAL: The goal of this study was to correlate upright and prone bolus transit time (BTT) on barium esophagography (BE) with esophageal peristalsis on high-resolution manometry (HRM) and self-reported dysphagia in patients with normal lower esophageal sphincter parameters on HRM. BACKGROUND: BTT on BE could be the gold standard for assessing the effectiveness of esophageal peristalsis if it can be quantified. MATERIALS AND METHODS: Patients with normal lower esophageal sphincter parameters and standard-protocol BE from 2017 to 2020 were included. Patients were divided, based on the number of normal swallows (distal contractile integral >450 mm Hg-s-cm), into 11 groups (10 normal swallows to 0 normal swallows). Liquid barium swallows in prone position were objectively evaluated for prone BTT. Patients reported difficulty in swallowing on a scale from 0 (none) to 4 (very severe). Fractional polynomial and logistic regression analysis were used to study the association (along with the rate of change) between BTT, peristalsis, and dysphagia. RESULTS: A total of 146 patients were included. Prone BTT increased as the number of normal swallows decreased ( P <0.001). Two deflection points were noted on the association between peristalsis and prone BTT at 50% normal swallows, 40 seconds and 30% normal swallows, 80 seconds, after which peristaltic function declined independently of prone BTT. Patients with prone BTT>40 seconds had nearly 6-fold higher odds of 0% normal swallows on HRM than patients with prone BTT<40 seconds ( P =0.002). Increasing prone BTT was associated with increasing dysphagia grades 1 and 2 ( P ≤0.036). CONCLUSIONS: Esophageal motility can be quantified by BE. Prone BTT correlates with the proportion of normal esophageal swallows and dysphagia.

Esophagogastric Junction Outflow Obstruction: Are We Missing Anything?

GOALS: The authors aimed to compare preperistaltic distal esophageal pressure in patients with esophagogastric junction outflow obstruction (EGJOO) with and without reported dysphagia. BACKGROUND: Manometric EGJOO is characterized by elevated integral relaxation pressure (>15 mm Hg) without achalasia. The nomenclature inherently implies that it should be associated with impaired food bolus transit and should theoretically present clinically as dysphagia. STUDY: The authors queried an esophageal functional test database to identify patients diagnosed with EGJOO. They excluded patients who presented with ≥2 swallows with abnormal (ie, weak, failed or hypercontractile) esophageal body motility. To elucidate differences in manometric findings, the authors formed 2 cohorts of patients on the basis of a standard esophageal symptom questionnaire: those without dysphagia and those with severe or very severe dysphagia. All studies were reanalyzed to determine the distal esophageal pressure before each peristaltic wave (ie, the preperistaltic pressure) for individual swallows. The Mann-Whitney U test was used to compare categorical variables between groups. The level of significance was set to P<0.05. RESULTS: In total, 149 patients were diagnosed with EGJOO during the study period. Of these, 42 patients with ≥9 (out of 10) peristalsis (20 without dysphagia and 22 with severe/very severe dysphagia) formed the study cohorts. Patients with severe dysphagia had significantly higher median preperistaltic pressures in the distal esophagus. Preperistaltic pressure measurements showed better sensitivity and specificity for dysphagia than integral relaxation pressure. CONCLUSIONS: Elevated preperistaltic pressure is noted in symptomatic EGJOO patients. Inclusion of preperistaltic pressure in the diagnostic criteria for EGJOO may increase the clinical relevance of manometric classification.

The role of miRNA-155 in the immunopathogenesis of obliterative airway disease in mice induced by circulating exosomes from human lung transplant recipients with chronic lung allograft dysfunction.

Human lung transplant recipients undergoing rejection induce circulatory exosomes with lung self-antigens (SAgs), K-alpha 1 Tubulin and Collagen V, and immunization of C57BL/6 mice with exosomes induced obliterative airway disease (HEI-OAD). We analyzed whether exosomes with SAgs induced immunity in microRNA-155 knockout mice (miR-155KO), as microRNA-155 is an immune regulator. C57BL/6 and miR-155KO were immunized with exosomes from stable or chronic rejection (bronchiolitis obliterans syndrome (BOS) and on day 30, induction of exosomes, antibodies (Abs) to SAgs and cellular immunity were determined. C57BL/6 immunized with exosomes from BOS developed OAD. These immunized animals also developed Abs to SAgs and increased frequency of SAg-specific IFNγ and IL17- producing cells. In contrast, Abs to SAgs did not develop in miR-155KO and there was reduction in frequency of cells producing IL10. Upregulation of suppressor of cytokine signaling for lung inflammation was also noted resulting in abrogation of induction of exosomes with SAgs OAD.

Clinical Symptom Presentation of Hypercontractile Peristalsis in the Era of High-Resolution Manometry: A Single-Center Experience.

BACKGROUND: Hypercontractile motility of the esophagus is occasionally noted on high-resolution manometry (HRM), but its clinical correlations are unclear. We compared symptom severity and clinical presentation of patients with hypercontractile motility of the esophagus. METHODS: This was a retrospective cohort study. We queried a prospectively maintained database for patients who underwent esophageal function testing from October 1, 2016, to October 30, 2018. We included patients with jackhammer esophagus (JE; ≥2 swallows with distal contractile integral [DCI] ≥8,000 mm Hg∙cm∙s), nutcracker esophagus (NE; mean DCI 5,000-8,000 mm Hg∙cm∙s without meeting JE criteria), or esophagogastric junction outflow obstruction ([EGJOO]: abnormal median integrated relaxation pressure (>15 mm Hg) without meeting achalasia criteria, with JE [EGJOO-h], or normal motility [EGJOO-n]). HRM, endoscopy, barium esophagram, ambulatory pH studies, and symptom questionnaires were reevaluated for further analysis. Clinical parameters were analyzed using Spearman Rho correlation. Categorical variables were assessed with Fisher exact or chi-square test. RESULTS: Altogether, 85 patients met inclusion criteria. They were divided into 4 subgroups: 28 with JE, 18 with NE, 15 with EGJOO-h, and 24 with EGJOO-n. Patients with EGJOO-h were the most symptomatic overall. No correlation was seen between symptoms and mean DCI (p ≥ 0.05 all groups) or number of hypercontractile swallows (≥8,000 mm Hg∙cm∙s, p ≥ 0.05). A significant correlation was noted between dysphagia and lower esophageal sphincter pressure (LESP) and LESP integral (p ≤ 0.05). CONCLUSION: The number of hypercontractile swallows and mean DCI were not associated with patient-reported symptoms. Elevated LESP may be a more relevant contributor to dysphagia.

Factors associated with skin cancer in lung transplant recipients: A single-center experience.

BACKGROUND: Skin cancer is common after solid organ transplantation, but few have investigated it after lung transplant (LTx). OBJECTIVE: We assessed incidence and predictors of non-melanoma skin cancer (NMSC) post-LTx. METHODS: We studied patients who underwent LTx at our center from 2012 to 2015. RESULTS: Of 287 patients, mean age was 59.6 ± 11 years, 170 (59.2%) were men, and 231 (80.5%) were white. Seventy-six (26.5%) developed NMSC over a median follow-up of 32 months (IQR, 23-45). Of those with NMSC, 37% developed subsequent skin cancer of the same type. Independent predictors of decreased odds of NMSC and squamous cell carcinoma (SCC) were non-white race (P = .002; P = .003) and body mass index >30 kg/m2 compared with underweight patients (P = .001, P = .009). Patients with skin cancer pre-LTx had higher risk of post-LTx skin cancer (P = .02). Voriconazole use ≥100 days was associated with increased risk of SCC (P = .03), but not increased risk of basal cell carcinoma. Out of 76, 4 (5.3%) died from skin cancer. LIMITATIONS: Retrospective, single-center study. CONCLUSION: Squamous cell carcinoma risk post-LTx may increase with prolonged voriconazole use in white patients with pre-LTx history of skin cancer, whereas excess body weight may be protective from NMSC. Regular pre- and post-LTx skin cancer screenings and guidelines are warranted.

Primary paraesophageal hernia repair with Gore® Bio-A® tissue reinforcement: long-term outcomes and association of BMI and recurrence.

BACKGROUND: Laparoscopic repair remains the gold-standard treatment for paraesophageal hernia (PEH). We analyzed long-term symptomatic outcomes and surgical reintervention rates after primary PEH repair with onlay synthetic bioabsorbable mesh (W. L. Gore & Associates, Inc., Flagstaff, AZ) and examined body mass index (BMI) as a possible risk factor for poor outcomes and for recurrence. METHODS: We queried a prospectively maintained database to identify patients who underwent laparoscopic primary PEH repair with onlay patch of a bioprosthetic absorbable mesh (Bio-A® Gore®) between 05/28/2009 and 12/31/2013. Electronic health records were accessed to record demographic and operative data and were reviewed up to the present to identify any repeat procedures. Patients were grouped according to preoperative BMI (A: BMI < 25; B: BMI = 25-29.9; C: BMI = 30-34.9; D: BMI ≥ 35). Patients completed standardized satisfaction and symptom surveys. RESULTS: In total, 399 patients were included. Most patients (n = 261; 65.4%) were women. Mean age was 59.6 ± 13.4 years; mean BMI was 29.9 ± 5.0 kg/m2. The patients were grouped as follows: A, 53 patients (13.3%); B, 166 (41.6%); C, 115 (28.8%); D: 65 (16.3%). Four procedures (1.0%) were converted from laparoscopy to open procedures. All patients underwent an antireflux procedure (225 Nissen, 170 Toupet, 4 Dor). A mean follow-up of 44.7 ± 22.8 months was available for 305 patients (76.4%). 24/305 patients (7.9%) underwent reoperation, and the number of reoperations did not differ among groups (P = 0.64). Long-term symptomatic outcomes were available for 217/305 patients (71.1%) at a mean follow-up of 54.0 ± 13.1  months; no significant difference was observed among groups. 194/217 patients (89.4%) reported good to excellent satisfaction, with no significant differences among the groups. CONCLUSIONS: Laparoscopic primary PEH repair with onlay Bio-A® mesh is a safe and feasible procedure with excellent long-term patient-centered outcomes and acceptable symptomatic recurrence rate. BMI does not appear to be related to the need for surgical reintervention.

Sleep, Nutrition, and Health Maintenance in Cardiothoracic Surgery.

Cardiothoracic surgeons work in high-intensity environments starting in surgical training and throughout their careers. They deal with critical patients. Their routine procedures are delicate, require extensive attention to detail, and can have detrimental effects on patients' lives. Cardiothoracic surgeons are required to perform at their best capacity incessantly. To do this, they must safeguard their mental and physical well-being. Preserving health through sleep, nutrition, exercise, and routine medical checkups ensures a cardiothoracic surgeon's well-being. Great personal effort and discipline is required to maintain health in a busy schedule. We offer our best recommendations from expert peers in the field.

Pulmonary and esophageal function in lung transplantation: Fundamental principles and clinical application.

The lungs and esophagus have a close anatomical and physiological relationship. Over the years, reflux-induced pulmonary injury has gained wider recognition, but the full effects of pulmonary disease on esophageal function are still unknown. Intrathoracic pressure dynamics potentially affect esophageal function, especially in patients with end-stage lung disease, both obstructive and restrictive. Lung transplantation is the only viable option for patients with end-stage pulmonary disease and has provided us with a unique opportunity to study these effects as transplantation restores the intrathoracic environment. Esophageal and foregut functional testing before and after transplantation provide insights into the pathophysiology of the foregut-pulmonary axis, such as how underlying pulmonary disease and intrathoracic pressure changes affect esophageal physiology. This review summarizes the available literature and shares the research experience of a lung transplant center, covering topics such as pre- and posttransplant foregut function, esophageal motility in lung transplant recipients, immune-mediated mechanisms of graft rejection associated with gastroesophageal reflux, and the role of antireflux surgery in this population.

Regulation of cardiac allograft immune responses by microRNA-155.

INTRODUCTION: A better understanding of the immune mechanisms involved in allograft rejection after transplantation is urgently needed to improve patient outcomes. As microRNA-155 (miR155) plays a critical role in inflammation, we postulated that a deficiency of miR155 will improve cardiac allograft survival and enhance tolerance induction after heart transplantation. METHODS: We developed an acute rejection mouse model through heterotopic BALB/c cardiac transplantation to C57BL/6 (wild-type) and C57BL/6 miR155 knock-out (miR155KO) mice. Further, we induced tolerance in both groups through a costimulatory blockade with CTLA4-Ig (200 µg; post-transplant day 2) and MRI antibodies (250 µg; post-transplant day 0), targeting CD28/B7 and CD40/CD154 signals, respectively. Finally, we examined the effects of injecting 100 µg of small extracellular vesicles (sEVs) isolated from wild-type mice undergoing rejection into tolerant miR155KO mice. RESULTS: Mean survival time (MST) of the cardiac allografts in wild-type and miR155KO mice was 7 and 15 days, respectively (p < 0.0001). Costimulatory blockade increased MST to 65 days and > 100 days in the wild-type and miR155KO recipients, respectively (p < 0.001). Injection of sEVs isolated from wild-type mice undergoing rejection into tolerant miR155KO mice decreased the allograft survival to 9 days, significantly lower than the tolerant miR155KO mice without injection of sEVs (>100 days; p < 0.0001). CONCLUSION: miR155KO mice have improved cardiac allograft survival and enhanced induction of tolerance after heterotopic cardiac transplantation. Injection of sEVs from wild-type mice undergoing rejection into the miR155KO mice reversed these benefits.