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Base editing is a revolutionary gene-editing technique enabling the introduction of point mutations into the genome without generating detrimental DNA double-stranded breaks. Base-editing enzymes are commonly delivered in the form of modified linear messenger RNA (mRNA) that is costly to produce. Here, we address this problem by developing a simple protocol for manufacturing base-edited cells using circular RNA (circRNA), which is less expensive to synthesize. Compared with linear mRNA, higher editing efficiencies were achieved with circRNA, enabling an 8-fold reduction in the amount of RNA required. We used this protocol to manufacture a clinical dose (1 × 108 cells) of base-edited chimeric antigen receptor (CAR) T cells lacking expression of the inhibitory receptor, PD-1. Editing efficiencies of up to 86% were obtained using 0.25 µg circRNA/1 × 106 cells. Increased editing efficiencies with circRNA were attributed to more efficient translation. These results suggest that circRNA, which is less expensive to produce than linear mRNA, is a viable option for reducing the cost of manufacturing base-edited cells at scale.
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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.
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Fuga Anastomótica , Neoplasias Esofágicas , Humanos , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Fuga Anastomótica/terapia , Esofagectomía/efectos adversos , Neoplasias Esofágicas/cirugía , Endoscopía Gastrointestinal/efectos adversos , Estudios Retrospectivos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anastomosis Quirúrgica/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: Gastro-oesophageal reflux disease after lung transplantation may be associated with chronic lung allograft dysfunction. Aspiration may continue on medical management of reflux, but antireflux surgery potentially reduces all reflux. We compared outcomes between medical and surgical management of reflux in lung recipients. METHODS: Lung recipients with an elevated DeMeester score (≥14.72) on post-transplant reflux testing between 2015 and 2020 were included. Patients were divided into 2 groups: group A (underwent surgery) and group B (medically managed). Endpoints were pulmonary function, allograft dysfunction-free survival and overall survival. Further analysis included subgroups: A1 (early surgery, <6 months) and A2 (late surgery, >6 months), and B1 (DeMeester <29.9) and B2 (DeMeester ≥30). RESULTS: A total of 186 included subjects were divided into groups A [n = 46 (A1, n = 36; A2, n = 10)] and B [n = 140 (B1, n = 78; B2, n = 62)]. Compared to medically managed patients, patients who underwent surgery had a higher prevalence of hiatal hernia (P < 0.001) and a lower prevalence of oesophageal motility disorders (P = 0.036). Recipients who underwent surgery had superior pulmonary function at 5 years compared to group B (P < 0.05) and longer allograft dysfunction-free survival than subgroup B2 (P = 0.028). Furthermore, early surgery was associated with longer survival than late surgery (P = 0.021). CONCLUSIONS: Antireflux surgery in recipients with reflux improved long-term allograft function, and early surgery showed a survival benefit. Allograft dysfunction-free survival of lung recipients who underwent surgery was significantly better than that of medically managed patients with DeMeester ≥30. We present an algorithm for appropriate selection of candidates for antireflux surgery after lung transplantation.
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Reflujo Gastroesofágico , Hernia Hiatal , Laparoscopía , Trasplante de Pulmón , Humanos , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/cirugía , Fundoplicación , Hernia Hiatal/cirugía , Pulmón , Estudios RetrospectivosRESUMEN
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.
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Reflujo Gastroesofágico , Laparoscopía , Trasplante de Pulmón , Adulto , Humanos , Reflujo Gastroesofágico/cirugía , Complicaciones Posoperatorias/epidemiología , Morbilidad , Fundoplicación , Resultado del TratamientoRESUMEN
Introduction: Incidentally detected malignancies in lung explants portend risk of early cancer recurrence and metastases with posttransplant immunosuppression. We present a series of lung transplant recipients with previously unverified malignancies in native lung explants. Design: We reviewed the histopathology, radiographic imaging, and management of lung explant malignancies at our institution over 10 years (2011-2020). Endpoints were survival and allograft rejection. Results: An explant malignancy was found in 1.3% (11/855) of lung transplant recipients (6 [55%] men; median age 68 years; 6 [55%] ex-smokers [median pack-years, 25]). Nine (82%) were adenocarcinoma, 1 (9%) was squamous cell carcinoma (SCC), and 1 (9%) was follicular lymphoma. Three patients (27%) had multifocal involvement (≥3 lobes), 4 (36%) had nodal involvement, and the median (range) tumor size was 2.7 (0.4-19) cm. The median interval between last imaging and transplant was 58 (29-144) days. Mycophenolate mofetil was discontinued or reduced in all; everolimus was used in 2 patients, and cisplatin-pemetrexed chemotherapy was used in 2 patients. The prevalence of acute cellular rejection and chronic rejection was 27% and 9%, respectively. Lung recipients with cancer had significantly lower survival than those without (36.4% vs 67.3%, p = 0.002); median survival was 27 (17, 65) months in 4 recipients who were alive and cancer-free at the end of the study period. Conclusions: Unidentified malignancies, commonly adenocarcinoma, can be detected in explanted native lungs. Pneumonectomy may be curative in SCC, lymphoproliferative disorders, and stage I adenocarcinoma. Modulating immunosuppression to prevent allograft rejection and tumor proliferation is warranted.
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Adenocarcinoma , Neoplasias Pulmonares , Trasplante de Pulmón , Masculino , Humanos , Anciano , Femenino , Trasplante de Pulmón/efectos adversos , Recurrencia Local de Neoplasia , Pulmón , Neumonectomía , Neoplasias Pulmonares/cirugía , Rechazo de Injerto/prevención & control , Adenocarcinoma/cirugía , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/etiología , Inmunosupresores/uso terapéutico , Estudios RetrospectivosRESUMEN
A conditioned flavor preference develops when hungry or thirsty rats experience a neutral flavor mixed in solution with a nutrient. In two sets of studies, we previously demonstrated that this learned preference is highly sensitive to flavor nonreinforcement (i.e., exposure to the flavor without the nutrient) either prior to (latent inhibition), during (partial reinforcement), or following (extinction) flavor-nutrient pairings. In each of these studies we employed a nutrient devaluation procedure to assess the integrity of specific flavor-nutrient associations following extinction, but more recently Gonzalez, Morillas, and Hall (Journal of Experimental Psychology: Animal Learning & Cognition, 42, 380-390, 2016) observed that sensitivity to extinction in thirsty rats in this preparation may depend upon use of a post-conditioning nutrient devaluation procedure. To assess the generality of our earlier results, but without including a post-conditioning nutrient devaluation phase, we assessed in three experiments the role of the number of flavor-nutrient pairings given prior to extinction and the possibility of spontaneous recovery following a 3-week delay. We observed that extinction consistently weakened the flavor preference in thirsty rats (in spite of the absence of a nutrient devaluation procedure) and also found no evidence for spontaneous recovery. These results establish that our prior findings that conditioned flavor preferences are weakened by extinction are quite robust in thirsty rats and that these extinction effects may be fairly permanent.
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Condicionamiento Psicológico , Preferencias Alimentarias , Animales , Hambre , Ratas , Refuerzo en Psicología , GustoRESUMEN
Rats were given repeated choices between social and nonsocial outcomes, and between familiar and unfamiliar social outcomes. Lever presses on either of 2 levers in the middle chamber of a 3-chamber apparatus opened a door adjacent to the lever, permitting 45-s access to social interaction with the rat in the chosen side chamber. In Experiment 1, rats preferred (a) social over nonsocial options, choosing their cagemate rat over an empty chamber, and (b) an unfamiliar over a familiar rat, choosing a non-cagemate over their cagemate. These findings were replicated in Experiment 2 with 2 different non-cagemate rats. Rats preferred both non-cagemate rats to a similar degree when pitted against their cagemate, but were indifferent when the 2 non-cagemates were pitted against each other. Similar preference for social over nonsocial and non-cagemate over cagemate was seen in Experiment 3, with new non-cagemate rats introduced after every third session. Response rates (for both cagemate and non-cagemate rats) were elevated under conditions of nonsocial (isolated) housing compared to conditions of social (paired) housing, demonstrating a social deprivation effect. Together, the experiments contribute to an experimental analysis of social preference within a social reinforcement framework, drawing on methods with proven efficacy in the analysis of reinforcement more generally.
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Refuerzo en Psicología , Conducta Social , Animales , RatasRESUMEN
A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning.SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner.
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Lateralidad Funcional/fisiología , Lóbulo Parietal/fisiología , Lóbulo Temporal/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Cognición , Método Doble Ciego , Femenino , Humanos , Masculino , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Percepción Social , Teoría de la Mente/fisiología , Estimulación Transcraneal de Corriente Directa , Adulto JovenRESUMEN
OBJECTIVE: Esophageal aperistalsis has been considered a relative contraindication for lung transplant because of a higher risk of allograft dysfunction secondary to reflux and aspiration induced by poor esophageal clearance. We previously reported that esophageal motility improves in some patients after lung transplant. We reviewed the clinical course of lung transplant recipients diagnosed with an aperistaltic esophagus on pretransplant testing. METHODS: We identified patients diagnosed with pretransplant aperistaltic esophagus on high-resolution manometry who underwent lung transplant. Recipients with normal esophageal motility before lung transplant were used as the propensity score-matched control group. High-resolution manometry was repeated after lung transplant, and patients with aperistalsis were further divided into 2 subgroups: improved esophageal peristalsis and nonimproved peristalsis (ie, persistent aperistalsis after lung transplant). RESULTS: Esophageal aperistalsis was seen in 31 patients (mean age, 59.0 years; 21 men). The 1-, 3-, and 5-year post-lung transplant survivals in the aperistalsis group were 80.6%, 51.2%, and 34.9%, respectively, which was significantly lower than in the control group (90.3%, 73.4%, and 58.8%, respectively; P = .038). Post-lung transplant high-resolution manometry was performed for 29 patients in the aperistalsis group, 19 of whom demonstrated improved esophageal motility (65.5%). The 1-, 3-, and 5-year survivals after lung transplant of patients with recovery of peristalsis were similar to those of the control group (89.5%, 65.0%, and 48.8%, respectively; P = 1.000), whereas the nonimproved peristalsis group had lower survival (80.0%, 36.0%, and data unavailable, respectively; P = .012). CONCLUSIONS: Esophageal aperistalsis is not necessarily a contraindication for lung transplant. Improved peristalsis can be expected in up to two-thirds of these patients and is associated with good outcomes.
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Trastornos de Deglución/fisiopatología , Esófago/fisiopatología , Reflujo Gastroesofágico/fisiopatología , Trasplante de Pulmón/métodos , Peristaltismo/fisiología , Recuperación de la Función , Insuficiencia Respiratoria/cirugía , Anciano , Monitorización del pH Esofágico , Esófago/metabolismo , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/complicaciones , Humanos , Masculino , Manometría , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Insuficiencia Respiratoria/complicaciones , Factores de TiempoRESUMEN
BACKGROUND: Esophageal dysmotility and gastroesophageal reflux disease are common in patients with advanced lung disease and can potentially affect outcomes of lung transplant; however, the effects of lung transplant on foregut function remain unknown. We assessed foregut function before and after bilateral lung transplant. METHODS: We attempted complete foregut function testing before and after lung transplant. We compared patients with obstructive lung disease and patients with restrictive lung disease who underwent lung transplant between 2015 and 2016. RESULTS: In total, 112 patients met inclusion criteria. The mean age of patients was 62.2 years, and 62 patients were men. A total of 51 patients (45.5%) were diagnosed with obstructive lung disease, and 56 patients (50.0%) were diagnosed with restrictive lung disease. Approximately half of these patients had a change in manometric diagnosis before and after lung transplant, with most achieving increased peristaltic vigor. Pre-lung transplant gastroesophageal reflux disease was more prevalent in the restrictive lung disease cohort than in the obstructive lung disease cohort (42.9% vs 19.6%, P = .010). Thoracoabdominal pressure gradient before lung transplantation was greater in the restrictive lung disease group than in the obstructive lung disease group (23.4 vs 14.7 mm Hg, P < .001), which may explain the mechanism of increased reflux in patients with restrictive lung disease. No differences were seen in the post-lung transplant prevalence of pathological reflux and thoracoabdominal pressure gradient between groups. CONCLUSIONS: Esophageal motility and reflux parameters vary significantly between patients with obstructive lung disease and patients with restrictive lung disease, and can be explained by differences in underlying pulmonary dynamics. Restoring pulmonary physiology after lung transplant ameliorates the effects of esophageal dysmotility and reflux. Improved peristaltic vigor after lung transplant in patients with hypomotility is important, which may make them eligible for antireflux surgery if gastroesophageal reflux disease persists after lung transplant.
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Trastornos de la Motilidad Esofágica/etiología , Reflujo Gastroesofágico/etiología , Trasplante de Pulmón/efectos adversos , Anciano , Endoscopía del Sistema Digestivo , Esófago/fisiopatología , Femenino , Vaciamiento Gástrico/fisiología , Humanos , Masculino , Manometría , Persona de Mediana EdadRESUMEN
Advanced age is associated with difficulties in social understanding. However, little is known about the underlying cognitive processes. In the present study, healthy young and older adults completed measures of implicit and explicit visual perspective taking (VPT) and measures of executive and social cognition across four experiments. Congruency effects (slower response times or reduced accuracy when scenes were incongruent with the alternate perspective) were identified for the egocentric ("self") and allocentric ("other") conditions of both Level 1 ("line of sight") and Level 2 ("egocentric transformation") explicit VPT. Older adults showed less influence of the alternate perspective during Level 1 VPT, as indexed by fewer errors when the alternate perspective was incongruent. However, during Level 2 VPT, compared with young adults, older adults showed greater influence of the allocentric perspective during egocentric judgments as indexed by slower response times when the scene was incongruent with the allocentric perspective. Older adults were also slower at taking the allocentric perspective in general across both Level 1 and 2 tasks. An implicit VPT effect was identified that was consistent across both age groups. Several VPT measures were associated with executive and social cognition, with different patterns in young and older adults suggesting differing underlying strategies or cognitive processes may partially explain VPT differences between the groups. Difficulties in higher order social tasks may arise from underlying cognitive processes involved in perspective taking and these may be different depending on the requirement to perform an egocentric transformation into the allocentric frame of reference. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Cognición/fisiología , Juicio/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Factores de Edad , Anciano , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiología , Conducta Social , Adulto JovenRESUMEN
Chronic airway inflammation and infection drive morbidity and mortality among patients with cystic fibrosis (CF). While Haemophilus influenzae and Staphylococcus aureus predominate in children, the prevalence of Pseudomonas aeruginosa increases as patients age. Other bacteria, including species within the Burkholderia cepacia complex (Bcc), are also more prevalent among adults with CF. Species within the Bcc accelerate lung function decline and can trigger development of "cepacia syndrome," both before and after lung transplantation. As a result, some centers advise against lung transplantation for Bcc-infected patients; however, little is known about the relative virulence of uncommon Bcc species. We describe a successful lung re-transplant in a patient with CF, chronic Burkholderia ambifaria airway infection, and cepacia syndrome.
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Bacteriemia/cirugía , Infecciones por Burkholderia/cirugía , Burkholderia/aislamiento & purificación , Fibrosis Quística/cirugía , Trasplante de Pulmón , Pulmón/diagnóstico por imagen , Adulto , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Infecciones por Burkholderia/diagnóstico , Infecciones por Burkholderia/microbiología , Fibrosis Quística/diagnóstico , Fibrosis Quística/microbiología , Femenino , Humanos , Pulmón/microbiología , Reoperación , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
We report the preparation and characterisation of a cocrystal of triphenylphosphine with 1,3,5-trifluoro-2,4,6-triiodobenzene. The structure features a rare example of phosphorus acting as a halogen bond acceptor.
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CASE PRESENTATION: A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18 months prior. His posttransplant course was fairly unremarkable until 1 month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening. A bronchoscopy with BAL and transbronchial biopsies did not show acute cellular rejection, but the BAL fluid was positive for coronavirus. His cortisol level was undetectable; he was diagnosed with adrenal insufficiency and fludrocortisone was initiated. He was taking prednisone, tacrolimus, and everolimus for immunosuppression and valganciclovir, itraconazole, and trimethoprim-sulfamethoxazole for antimicrobial prophylaxis. His 25-lb weight loss occurred over the span of just one month.
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Adenocarcinoma del Pulmón/complicaciones , Disnea/etiología , Trasplante de Pulmón/efectos adversos , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Receptores de Trasplantes , Pérdida de Peso , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/secundario , Anciano , Biopsia , Disnea/diagnóstico , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , MasculinoRESUMEN
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.
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Índice de Masa Corporal , Hernia Hiatal/cirugía , Herniorrafia/métodos , Laparoscopía/métodos , Mallas Quirúrgicas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Recurrencia , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Factores de TiempoRESUMEN
Despite recent advances in screening methods, lung cancer remains the leading cause of cancer-related deaths worldwide. By the time lung cancer becomes symptomatic and patients seek treatment, it is often too advanced for curative measures. Low-dose computed tomography (CT) screening has been shown to reduce mortality in patients at high risk of lung cancer. We present a 66-year-old man with a 50-pack-year smoking history who had a right upper lobe (RUL) pulmonary nodule and left lower lobe (LLL) consolidation on a screening CT. He reported a weight loss of 45 pounds over 3 months, had recently been hospitalized for hyponatremia, and was notably cachectic. A CT of the chest showed a stable LLL mass-like consolidation and a 9 × 21 mm subsolid lesion in the RUL. Navigational bronchoscopy biopsy of the RUL lesion revealed squamous non-small cell lung cancer (NSCLC). Endobronchial ultrasound-guided transbronchial needle aspiration of the LLL lesion revealed small cell lung cancer (SCLC). The final diagnosis was a right-sided Stage I NSCLC (squamous) and a left-sided limited SCLC. The RUL NSCLC was treated with stereotactic radiation; the LLL SCLC was treated with concurrent chemotherapy and radiation. In patients with multiple lung nodules, a diagnosis of synchronous multiple primary lung cancers (MPLCs) is crucial, as inadvertent upstaging of patients with MPLC (to T3 and/or T4 tumors) can lead to erroneous staging, inaccurate prognosis, and improper treatment. Recent advances in the diagnosis of small pulmonary nodules via navigational bronchoscopy and management of these lesions dramatically affect a patient's overall prognosis.
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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.
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Fundoplicación/estadística & datos numéricos , Reflujo Gastroesofágico/cirugía , Trasplante de Pulmón/estadística & datos numéricos , Anciano , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Tiempo de TratamientoRESUMEN
Background Preoperative atrial fibrillation is associated with poor outcomes after cardiac surgery, but its effect on lung transplantation outcomes remains unknown. Methods We retrospectively reviewed the charts of 235 patients who underwent lung transplantation in our institution from 2013 to 2015, analyzing demographics, length of stay, survival, readmissions, and cardiac events. Mean recipient age was 59 ± 11 years, and 142 (60.4%) were men. Patients were grouped according to pre-transplantation atrial fibrillation status (atrial fibrillation/no atrial fibrillation). Results The atrial fibrillation group ( n = 38; 16.2%) was significantly older with a longer ischemic time, more postoperative atrial arrhythmias (73.7% vs. 20.8%, p = 0.01), and a longer median postoperative length of stay (16 vs. 13 days, p = 0.02). The median total hospital stay in the first postoperative year was also higher in the atrial fibrillation group (27 vs. 21 days, p = 0.25). Short-term survival and survival during follow-up did not differ significantly between groups. Conclusions Lung transplant recipients with preoperative atrial fibrillation are at increased risk of adverse cardiovascular outcomes and longer hospital stay. Preoperative atrial fibrillation may portend adverse events after lung transplantation.
Asunto(s)
Fibrilación Atrial/complicaciones , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/mortalidad , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Complicaciones Posoperatorias/etiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic lung allograft dysfunction (CLAD) is nonreversible and remains the biggest obstacle to long-term survival after lung transplantation (LTx). Retransplantation is the sole definitive therapeutic option for CLAD. We analyzed our single-center experience with retransplantation as a treatment option for CLAD. METHODS: From March 1, 2010, to May 31, 2016, 419 consecutive patients underwent LTx at our institution; 29 of these procedures were retransplantations for CLAD. We analyzed demographic characteristics, lung allocation score, operation type, length of stay, and perioperative outcomes. Actuarial survival was estimated using Kaplan-Meier survival curves. RESULTS: In total, 29 of 419 patients (6.9%) underwent retransplantation for CLAD. Median time from primary LTx to retransplantation was 1,163 days (range: 304 to 3,971 days). Patients undergoing retransplantation were younger and had higher lung allocation scores than primary transplantation patients. Most LTx procedures were bilateral (93% of retransplantations, 95% of primary LTx). Rates of cardiopulmonary bypass, extracorporeal membrane oxygenation support for severe primary graft dysfunction, and re-exploration for bleeding were higher in retransplantation patients (p = 0.010, p = 0.019, and p = 0.029, respectively). One- and 5-year survival rates in the retransplantation group were similar to those of the primary LTx group (89.2% and 64.3% versus 89.7% and 58.2%, respectively; p = 0.79). CONCLUSIONS: Lung retransplantation is a viable treatment option for CLAD after LTx. In this study, retransplantation patients were younger, had higher lung allocation scores, and were more likely to require cardiopulmonary bypass and postoperative extracorporeal membrane oxygenation support than primary LTx patients. Postoperative length of stay and short- and mid-term survival were comparable with those of primary LTx patients.
Asunto(s)
Rechazo de Injerto/cirugía , Trasplante de Pulmón , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios RetrospectivosRESUMEN
OBJECTIVE: Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. METHODS: We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. RESULTS: Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. CONCLUSIONS: Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status. Long-term outcomes are being studied.