A potential mechanism by which aspiration of duodenogastric fluid augments the risk for bronchiolitis obliterans syndrome after lung transplantation.

OBJECTIVE: Aspiration of duodenogastric refluxate may damage the respiratory epithelium of lung allografts in transplant recipients. We sought to define a mechanism by which aspiration of duodenogastric fluid augments the risk of bronchiolitis obliterans syndrome after lung transplant in a murine model. METHODS: We analyzed the immunological effects of acute aspiration of duodenogastric fluid (0.5 mL/kg) on transplant naive (strain DBA/2J) and transplanted mice (strain B6D2F1/J to strain DBA/2J). Serum antibodies to the lung self-antigens (SAgs) K-alpha1 tubulin and collagen-V were determined by enzyme-linked immunosorbent assay. Exosomes were isolated from serum, and immunoblot membranes were probed for antibodies to lung SAgs. Lung sections were assessed for fibrotic burden and obliterative bronchiolitis lesions by histologic and immunohistochemical analyses, including trichrome staining. RESULTS: Transplanted mice that received duodenogastric fluid developed higher levels of antibodies to the lung SAgs K-alpha1 tubulin and collagen-V and exosomes with lung SAgs on posttransplant days 14 and 28 than transplanted mice with sham aspiration or transplant naive mice (with and without aspiration). All lung allografts demonstrated severe grade A4 rejection on posttransplant day 14, with the highest mean fibrotic burden and mean number of obliterative bronchiolitis-like lesions per microscopic field on day 28 in recipients with aspiration. CONCLUSIONS: This study links aspiration of duodenogastric fluid after lung transplant to higher autoimmune responses to lung SAgs and the release of circulating exosomes with lung SAgs, which together promote sustained immune responses leading to extensive lung parenchymal damage and, ultimately, severe obliterative bronchiolitis-the histologic hallmark of bronchiolitis obliterans syndrome.

Hospitalized patients with irreversible lung injury from COVID-19 have higher morbidity but similar 1-year survival after lung transplant compared to hospitalized patients transplanted for restrictive lung disease.

BACKGROUND: Hospitalized lung transplant (LT) recipients (LTRs) have higher post-LT morbidity and mortality than those who are well enough to wait for transplant at home. Outcomes after LT for COVID-19-associated acute respiratory distress syndrome (CARDS) may be even worse; thus, we compared post-LT outcomes between hospitalized LTRs transplanted for CARDS and those transplanted for restrictive lung disease (RLD). METHODS: Between 2014 and 2021, hospitalized LTRs ≥18 years old with CARDS or RLD were included. Primary and secondary outcomes were 1-year post-LT survival and postoperative morbidity. For each patient in the CARDS group, an analysis of 1-to-1 matched patients from the RLD group was performed using logistic regression modeling. RESULTS: Of 764 LTRs, 163 (21.3%) were hospitalized at the time of LT; 132 met the inclusion criteria: 11 (8.3%) were transplanted for CARDS and 121 (91.7%) for RLD. LTRs with CARDS were younger with longer pre-LT hospitalization stays and higher rates of pretransplant mechanical ventilation, dialysis, and ECMO as a bridge to transplant. A propensity-matched analysis demonstrated comparable rates of intrathoracic adhesions, posttransplant duration of mechanical ventilation, PGD3 at 72 hours, and delayed chest closure. Compared to LTRs with RLD, those with CARDS had significantly longer posttransplant hospital stays and a higher prevalence of ACR ≥A2 and DSA >2000 MFI, but comparable 1-year survival rates. CONCLUSION: Even with careful selection, LT for patients with CARDS was associated with significant morbidity; however, 1-year survival of recipients with CARDS was comparable to that of matched hospitalized recipients with RLD.

A Rare Case of Orthostasis, Dizziness, and Non-O1, Non-O139 Vibrio cholerae Infection in a Lung Transplant Recipient.

Non-O1, non-O139 Vibrio cholerae are rare strains that are generally nonpathogenic in immunocompetent hosts. However, this pathogen has been shown to cause gastroenteritis, wound infections, or bacteremia in immunocompromised patients and is associated with significant mortality in these hosts. Herein, we describe a case of hemorrhagic enterocolitis in a lung transplant recipient with an atypical presentation of non-O1, non-O139 V. cholerae and ongoing orthostasis. The patient reported recent seafood consumption and was managed appropriately with antibiotic therapy before necessitating esophagogastroduodenoscopy (EGD) for further objective testing.

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.

Antibody-Mediated Rejection and Sponge Effect in a Redo Lung Transplant Recipient.

Long-term survival after lung transplant remains severely limited by chronic lung allograft dysfunction. Antibody-mediated rejection of lung transplant allografts is usually caused by donor-specific antibodies (DSAs) directed toward donor human leukocyte antigens (HLAs). Typically, patients with antibody-mediated rejection have significantly higher circulating DSAs and increased mean fluorescence intensity than those without antibody-mediated rejection. However, some patients with antibody-mediated rejection have low mean fluorescence intensities, partly due to the "sponge effect" related to DSAs binding to HLA molecules within the lung. Herein, we report the case of an 18-year-old, female lung transplant recipient who required retransplantation and developed circulating DSAs directed toward the first allograft but detected in circulation only after retransplantation. The present case draws attention to a rare finding of sponge effect in a patient with antibody-mediated rejection leading to allograft failure.

Inpatient Lung Transplant Evaluation Is Associated With Increased Risk of Morbidity, Mortality, and Cost of Care After Transplant.

Lung transplantation is an important option for patients with end-stage lung disease. Many of these patients deteriorate rapidly and require inpatient care at the time of the transplant evaluation. RESEARCH QUESTION: How does the setting of lung transplant evaluation relate to perioperative outcomes, short-term postoperative outcomes, and healthcare costs accrued after transplant? DESIGN: We reviewed the records of patients who underwent primary, bilateral lung transplantation at our center between January 1, 2014 and May 31, 2016. Patient evaluation setting was categorized as inpatient, outpatient, or combined. Demographics, clinical characteristics, and cost of care were assessed. RESULTS: The study included 207 patients: 40 (19.3%) evaluated as inpatients, 146 (70.5%) as outpatients, and 21 (10.1%) as combined. Inpatients had the highest mean lung allocation scores (71.2 vs 49.7 [combined] and 40.8 [outpatient]; P < 0.001), lowest functional status at listing (P < 0.001), highest number of blood products used during surgery (P < 0.001), highest incidence of re-exploration for bleeding (P = 0.006), and longest posttransplant hospital stays (median, 35 vs 15 days [combined] and 12 days [outpatient]; P < 0.001). One-year survival trended lower for inpatients (log-rank, P = 0.056). Inpatient evaluations had the highest total, variable, and fixed costs of posttransplant care (P < 0.001). CONCLUSION: Inpatient lung transplant evaluation was associated with longer hospital stays, higher perioperative morbidity, and lower 1-year survival. Partial or complete inpatient evaluation was associated with a higher cost of care posttransplant.

Doppler-derived renal resistive index helps predict acute kidney injury in patients undergoing living-related liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is commonly associated with increased postoperative morbidity in liver transplant (LT) recipients. The aim of this study was to identify the role of renal resistive index (RRI) in predicting AKI and to study the factors associated with AKI in LT recipients. PATIENTS AND METHODS: We performed a single-center, prospective study, including adult living donor LT recipients at our center between January 2018 and September 2019 with no preoperative renal dysfunction. RRI was calculated on ultrasound doppler once preoperatively, and once daily in the postoperative period through postoperative day (POD) six. Patients were grouped into AKI and non-AKI groups for comparison. RESULTS: Fifty patients were included in the study (mean age, 44 years; 20% females). AKI developed in 25 patients (50%). Both groups were similar in baseline characteristics. RRI of ≥ 0.69 on POD 2 predicted AKI (sensitivity 88%; specificity 92%). RRI on the day before AKI diagnosis (0.71 vs. 0.65) and on the day of diagnosis (0.72 vs. 0.65) were significantly increased relative to preoperative baseline. CONCLUSIONS: Doppler-derived RRI is a rapid, non-invasive, and bedside procedure capable of predicting the occurrence of postoperative AKI in LT recipients.

An update on current treatment strategies for managing bronchiolitis obliterans syndrome after lung transplantation.

INTRODUCTION: Bronchiolitis obliterans syndrome (BOS), a subtype of chronic lung allograft dysfunction, is quite common, with up to half of all lung recipients developing BOS within 5 years of transplantation. Preventive efforts are aimed at alleviating known risk factors of BOS development, while the primary goal of treatment is to delay the irreversible, fibrotic airway changes, and progressive loss of lung function. AREAS COVERED: This narrative review will briefly discuss the updated definition, clinical presentation, pathogenesis, risk factors, and survival after BOS while paying particular attention to the salient evidence for optimal preventive strategies and treatments based on investigations in the modern era. EXPERT OPINION: Future translational research focused on further characterizing the complex interplay between immune and nonimmune mechanisms mediating chronic lung rejection is the first step toward mitigating risk of allograft injury, improving early disease detection with noninvasive biomarkers, and ultimately, developing an effective, targeted therapy that can extend the life of the lung allograft.

Current trends in candidate selection, contraindications, and indications for lung transplantation.

Lung transplantation is an established treatment option that can improve quality of life and prolong survival for select patients diagnosed with end-stage lung disease. Given the gaps in organ donation and failures to make effective use of available organs, careful selection of candidates for lung transplant remains one of the most important considerations of the transplant community. Toward this end, we briefly reviewed recent trends in pretransplant evaluation, candidate selection, organ allocation, and organ preservation techniques. Since the latest consensus statement regarding appropriate selection of lung transplant candidates, many advances in the science and practice of lung transplantation have emerged and influenced our perspective of 'contraindications' to transplant. These advances have made it increasingly possible to pursue lung transplant in patients with risk factors for decreased survival-namely, older recipient age, increased body mass index, previous chest surgery, poorer nutritional status, and presence of chronic infection, cardiovascular disease, or extrapulmonary comorbid conditions. Therefore, we reviewed the updated evidence demonstrating the prognostic impact of these risk factors in lung transplant recipients. Lastly, we reviewed the salient evidence for current trends in disease-specific indications for lung transplantation, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, emphysema due to alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension, among other less common end-stage diseases. Overall, lung transplant remains an exciting field with considerable hope for patients as they experience remarkable improvements in quality of life and survival in the modern era.

A Collective Review of Gore Bio-A Absorbable Synthetic Mesh in Cruroplasty Reinforcement.

Background: Laparoscopic repair of hiatal hernia (HH) is associated with a considerable failure rate. Compared to suture repair alone, mesh-reinforced cruroplasty may be associated with fewer short-term recurrences, yet its use remains controversial. The aim of this study was to analyze the current literature assessing the use of Bio-A absorbable synthetic mesh in the reinforcement of primary crural closure after laparoscopic HH repair. Methods: A systematic review of primary literature in the MEDLINE and PubMed databases was conducted. We searched for investigations reporting patient outcomes in laparoscopic HH repair with onlay Gore Bio-A tissue reinforcement (W. L. Gore & Associates, Inc.) published between January 2008 and December 2019. The primary outcome was anatomical recurrence rate. Secondary outcomes were complication rate, symptomatic outcomes, and mortality. Results: Eight studies met inclusion criteria. There were two prospective and six retrospective cohort studies. In the included studies, laparoscopic HH repair was performed with Bio-A absorbable synthetic mesh in 734 patients. The anatomical recurrence data were extracted across all studies, and an objective recurrence was identified in 21/280 (7.5%) patients. There was only 1 (0.17%) mesh-related complication in the included studies. Conclusions: The use of Bio-A absorbable synthetic mesh in the repair of HHs may be promising, as it offers low rates of anatomical recurrence and mesh-related complications, but more data are still necessary to validate these findings. This collective review of literature is a basis for future randomized controlled trials to identify the most effective and safe mesh in the long term.

Esophageal cancer: challenges, concerns, and recommendations for management amidst the COVID-19 pandemic.

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, raising great concern, particularly in immunosuppressed cancer patients. The pandemic situation remains extremely dynamic, which necessitates proactive management decisions from oncologists and oncologic surgeons in effort to mitigate the risk of both SARS-CoV-2 infection and cancer metastasis. Esophageal cancer, in particular, is one of the deadliest types of malignancy worldwide, reflecting both aggressive biology and a lack of adequate treatment. Several challenges and concerns regarding the management of esophageal cancer have been raised in light of the ongoing viral pandemic. The primary aim of this review is to summarize the salient evidence for recommendations and optimal treatment strategies for patients with esophageal cancer amidst the COVID-19 pandemic.

Management and Outcomes of Diverticulitis After Lung Transplantation.

INTRODUCTION: Most lung transplant patients are older than 50 years. Complications from colonic diverticula are not uncommon, especially with chronic immunosuppression. However, limited data exist regarding the optimal management of these patients. We sought to investigate the incidence, risk factors, and outcomes of diverticulitis after lung transplant. METHODS: We conducted a retrospective study to review patients undergoing lung transplant between 2007 and 2016 with posttransplant acute colonic diverticulitis. Patients were grouped based on medical or surgical management. RESULTS: Of 512 transplant recipients, 17 (3.32%) developed 26 episodes of diverticulitis over a median follow-up of 39 months. Nine patients had documented diverticulosis on pretransplant colonoscopy. These patients had a higher incidence of surgical intervention for diverticulitis, were more likely to have recurrent diverticulitis, and had longer lengths of stay than patients without pretransplant diverticulosis. Six (35.3%) of 17 patients required surgery (ie, Hartmann procedure; 4 during the initial episode and 2 during their third and fourth episodes); 11 patients (64.7%) were managed with antibiotics alone. Patients in the surgical group presented earlier posttransplant (P = .004) and were on higher doses of tacrolimus (P = .03). Six (46.1%) of 13 patients with medically managed first episodes of diverticulitis experienced recurrence. No recurrence occurred after surgical management. No deaths were attributable to diverticulitis in either group. CONCLUSIONS: Patients with pretransplant diverticulosis experienced earlier, more complicated episodes of diverticulitis posttransplant than patients without. Surgical patients received higher doses of tacrolimus and presented earlier than medical patients. Uncomplicated diverticulitis in posttransplant patients can be managed medically, even in the case of recurrent, uncomplicated disease.

Enhanced recovery pathways vs standard care pathways in esophageal cancer surgery: systematic review and meta-analysis.

Enhanced recovery after surgery (ERAS) protocols vs standard care pathways after esophagectomy for malignancy have gained wide popularity among surgeons. However, the current literature is still lacking level-I evidence to show a clear superiority of one approach. The present study is a detailed systematic review and meta-analysis of the published trials. A systematic review of literature databases was conducted for randomized controlled trials (RCTs) and non-randomized, prospective, comparative studies between January 1990 and September 2019, comparing ERAS pathway group with standard care for esophageal resection for esophageal cancer. Mean difference (MD) for continuous variables and odds ratio (OR) or risk difference (RD) for dichotomous variables with 95% confidence interval (CI) were used. Between-study heterogeneity was evaluated. Eight studies with a total of 1133 patients were included. Hospital stay [Standard mean difference (Std. MD) = - 1.92, 95% CI - 2.78, - 1.06, P < 0.0001], overall morbidity (OR 0.68, CI 0.49, 0.96, P = 0.03), pulmonary complications (OR 0.45, CI 0.31, 0.65, P < 0.0001), anastomotic leak rate (OR 0.37, CI 0.18, 0.74, P = 0.005), time to first flatus and defecation (Std. MD = -5.01, CI - 9.53, - 0.49, P = 0.03), (Std. MD = - 1.36, CI - 1.78, - 0.94, P < 0.00001) and total hospital cost (Std. MD = - 1.62, CI - 2.24, - 1.01, P < 0.00001) favored the ERAS group. Patients who undergo ERAS have a clear benefit over the standard care protocol. However, existing protocols in different centers are followed by great variability, while the evaluated parameters suffer from significant heterogeneity. A well-formulated, standardized protocol should be standard-of-care at all centers.

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.

A Decade of Investigation: Peroral Endoscopic Myotomy Versus Laparoscopic Heller Myotomy for Achalasia.

Background: Although laparoscopic Heller myotomy (LHM) with partial fundoplication has long been considered the gold standard for treatment of patients with achalasia, peroral endoscopic myotomy (POEM) has emerged in the last decade as a viable alternative. Methods: A collective review of literature concerning investigations that have reported patient outcomes and treatment success of LHM and POEM for all achalasia subtypes. Results: While POEM has shown excellent short-term safety and efficacy in the relief of symptoms, the long-term symptomatic outcomes after the intervention are yet to be concluded. Further evaluation of patients' interpretations and answers on subjective questionnaires is warranted before determining treatment success for POEM. Use of more reliable and disease-specific health-related quality-of-life questionnaires are better justified when comparing a new endoscopic procedure to an established gold standard. The need for objective parameters to measure reflux, longer follow-up studies, and randomized trials comparing POEM to LHM is particularly important when assessing the outcome of this new technique. High incidence of post-POEM pathologic reflux and indication for daily proton pump inhibitor use is of concern, and the lack of more long-term, objective evidence leaves the clinical value of the procedure in a state of uncertainty. Conclusions: The LHM combined with partial fundoplication is still considered to be the gold standard treatment modality for achalasia, but as the POEM procedure rapidly becomes common practice, this treatment may be performed in the majority of achalasia cases. Given the number of flaws overlooked in seminal investigations, careful consideration should be given to the patients being selected for this therapy.

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.

Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is prevalent after lung transplantation. Fundoplication slows lung function decline in patients with GERD, but the optimal timing of fundoplication is unknown. METHODS: We retrospectively reviewed patients who underwent fundoplication after lung transplantion at our center from April 2007 to July 2014. Patients were divided into 2 groups: early fundoplication (<6 months after lung transplantation) and late fundoplication (≥6 months after lung transplantation). Annual decline in percent predicted forced expiratory volume in 1 second (FEV1) was analyzed. RESULTS: Of the 251 patients who underwent lung transplantation during the study period with available pH data, 86 (34.3%) underwent post-transplantation fundoplication for GERD. Thirty of 86 (34.9%) had early fundoplication and 56 of 86 (65.1%) had late fundoplication. Median time from lung transplantation to fundoplication was 4.6 months (interquartile range, 2.0-5.2) and 13.8 months (interquartile range, 9.0-16.1) for the early and late groups, respectively. The median DeMeester score was comparable between groups. One-, 3-, and 5-year actuarial survival rates in the early group were 90%, 70%, and 70%, respectively; in the late group, these rates were 91%, 66%, and 66% (log rank P = .60). Three- and 5-year percent predicted FEV1 was lower in the late group by 8.9% (95% confidence interval, -30.2 to 12.38; P = .46) and 40.7% (95% confidence interval, -73.66 to -7.69; P = .019). A linear mixed model showed a 5.7% lower percent predicted FEV1 over time in the late fundoplication group (P < .001). CONCLUSIONS: In this study, patients with early fundoplication had a higher FEV1 5 years after lung transplantation. Early fundoplication might protect against GERD-induced lung damage in lung transplant recipients with GERD.