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BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.
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Cuidadores , Ejercicio Físico , Neoplasias Pulmonares , Calidad de Vida , Humanos , Anciano , Neoplasias Pulmonares/cirugía , Masculino , Femenino , Teléfono , Atención Perioperativa/métodosRESUMEN
Atrial myxoma is a rare primary tumour of the heart that typically arises from the left atrium. Patients typically present with obstructive symptoms such as dyspnoea, but constitutional and embolic symptoms can be seen as well. Gastrointestinal symptoms in the absence of embolisation are rarely reported in the literature. Our case presents a 55-year-old female who was found to have a large left atrial myxoma after presenting with gastrointestinal symptoms, which resolved upon resection of the tumour. This case illustrates that atrial myxomas can have an atypical presentation with gastrointestinal symptoms, which could be related to inflammation of gastric mucosa from interleukin-6 produced by the tumour cells. Careful history-taking followed by early detection and prompt treatment is important as atrial myxomas can lead to potentially devastating complications. LEARNING POINTS: Atrial myxomas are primary tumours of the heart that can present with a wide spectrum of symptoms.Early consideration and recognition of atypical presentations of atrial myxomas can be crucial in preventing serious consequences such as cardiac arrest.
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The tricarboxylic acid (TCA) cycle plays a crucial role in mitochondrial ATP production in the healthy heart. However, in heart failure, the TCA cycle becomes dysregulated. Understanding the mechanism by which TCA cycle genes are transcribed in the healthy heart is an important prerequisite to understanding how these genes become dysregulated in the failing heart. PGC-1α is a transcriptional coactivator that broadly induces genes involved in mitochondrial ATP production. PGC-1α potentiates its effects through coactivation of coupled transcription factors, such as ERR, Nrf1, Gabpa, and YY1. We hypothesized that PGC-1α plays an essential role in transcription of TCA cycle genes. Thus, by utilizing localization peaks of PGC-1α to TCA cycle gene promoters, it would allow the identification of coupled transcription factors. PGC-1α potentiated the transcription of 13 out of 14 TCA cycle genes, partly through ERR, Nrf1, Gabpa, and YY1. ChIP-sequencing showed PGC-1α localization peaks in TCA cycle gene promoters. Transcription factors with binding elements that were found proximal to PGC-1α peak localization were generally essential for transcription of the gene. These transcription factor binding elements were well conserved between mice and humans. Among the four transcription factors, ERR and Gabpa played a major role in potentiating transcription when compared to Nrf1 and YY1. These transcription factor-dependent PGC-1α recruitment was verified with Idh3a, Idh3g, and Sdha promoters with DNA binding assay. Taken together, this study clarifies the mechanism by which TCA cycle genes are transcribed, which could be useful to understand how those genes are dysregulated in pathological conditions.
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BACKGROUND: The cardiothoracic surgical trainees perceive a need for more instruction and exposure to robotic-assisted thoracoscopic surgery (RATS) during their training. We sought to assess utilization and trainee exposure to robotic surgery in thoracic residency programs to identify areas for improvement. METHODS: A voluntary electronic survey of 10 questions was distributed to surgeons working in all thoracic surgery residency programs in the United States. The survey asked to provide the size of the residency, the availability and utilization of robots, and the trainee's adoption of robotic surgery in their practice after graduation. Multivariable logistic regression was performed with Stata MP version 17.0 (College Station, TX). RESULTS: Of a total of 76 cardiothoracic surgery training programs, surgeons from 69 training programs completed the survey (90.8%). The majority of pulmonary lobectomy was performed using robotic surgery (55%). About half of the training programs (35/69) have a formal robotic curriculum for the residents. Of 121 thoracic-track trainees, 118 trainees (97.5%) performed robotic surgery as part of their practice, while 62 of 110 (56.4%) cardiothoracic (CT) track and 16 of 158 (10.1%) cardiac-track trainees performed robotic surgery. In a multivariate analysis, the adoption of robotic surgery was associated with having an established robotic training curriculum (OR 5.82, 95% CI 1.32 - 35.7), and a larger training program (OR 3.78, 95% CI 1.34 - 10.6). CONCLUSIONS: A disparity exists in robotic surgical training among the training programs. A standardized curriculum and formal case requirements may be needed to ensure optimal preparation for future graduates.
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BACKGROUND: Minimally invasive esophagectomy is associated with decreased postoperative complications compared with open esophagectomy. However, the risks of complications for minimally invasive esophagectomy compared with open esophagectomy may be affected by operative time. The objectives of this study are to (1) compare the incidence of postoperative complications for minimally invasive esophagectomy and open esophagectomy and (2) evaluate the association of postoperative complications on operative approach and operative time. METHODS: A retrospective cohort analysis of patients who underwent an esophagectomy in the American College of Surgeons National Surgical Quality Improvement Program Procedure-Targeted Data File was performed from 2016 to 2020. For analysis, minimally invasive esophagectomy and open esophagectomy were stratified into tertiles of operative time. A bivariate analysis of postoperative complications comparing minimally invasive esophagectomy with open esophagectomy was performed. Multivariable Poisson regression models were estimated evaluating the association of the likelihood of postoperative complications with operative approach and operative time. RESULTS: In total, 8,574 patients who underwent esophagectomy were included: 5,369 patients underwent minimally invasive esophagectomy, and 3,205 patients underwent open esophagectomy. Median operative time was 402 minutes for minimally invasive esophagectomy and 321 minutes for open esophagectomy. The incidence of postoperative complications and 30-day mortality was lower in the minimally invasive esophagectomy group than the open esophagectomy group within the same tertiles of operative time. When we compared patients who underwent short open esophagectomy with those who underwent long minimally invasive esophagectomy, there were no significant differences in complications. CONCLUSION: There is no significant association of postoperative complications for short open esophagectomy compared with long minimally invasive esophagectomy. Patients should be selected for minimally invasive esophagectomy when there is appropriate surgeon experience and hospital resources.
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INTRODUCTION: Some papers suggest that wide-awake flexor tendon repair (FTR) may reduce rates of postoperative tendon gapping and rupture due to improved intraoperative testing of the repair. The current study is a nationwide cohort study comparing FTRs performed wide-awake and with traditional anesthesia. METHODS: Patients undergoing zone II FTR between 2010-2022 were identified in PearlDiver. Exclusion criteria were other tendon repairs, concomitant treatment for vascular injury, fracture, dislocation or amputation, inpatient or office surgery, age <18 years and <1 year of follow-up. Patients were stratified by anesthesia technique: traditional anesthesia (general anesthesia, monitored anesthesia care, regional blocks) or wide-awake. Patients were matched based on age, sex, Elixhauser Comorbidity Index (ECI) score, geographical region, insurance coverage, number of tendon repairs and presence of concomitant nerve repair. 30-day wound complications, emergency department visits and readmissions and 1-year reoperations were identified. Total reimbursement for surgery was determined. RESULTS: Each matched cohort included 2,563 patients. Wide-awake patients had fewer 30-day emergency department visits (2.7% vs 4.8%). There were no differences in 30-day wound complications or readmissions. There was no difference in 1-year reoperations for rupture or for stiffness. Multivariable linear regression identified wide-awake surgery to be a significantly associated with lower total reimbursement. CONCLUSIONS: Performing digital FTR using wide-awake techniques can reduce costs, but the hypothesis that wide-awake repairs may reduce rates of tendon rupture was not supported by the current study.
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BACKGROUND: Endoscopic posterior cervical foraminotomy is gaining popularity among endoscopic spine surgeons for the treatment of radiculopathy caused by foraminal stenosis. METHODS: This study describes a technique using the lateral decubitus position for endoscopic posterior cervical foraminotomy under monitored anesthesia care and local anesthesia only. RESULTS: A total of 10 patients with contraindications to general anesthesia underwent the procedure, resulting in improvement in cervical radicular pain with no perioperative complications. CONCLUSIONS: The findings suggest that this approach is a viable alternative for patients at high risk of general anesthesia care, expanding the surgical options for the treatment of radiculopathy.
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Anestesia Local , Vértebras Cervicales , Foraminotomía , Humanos , Foraminotomía/métodos , Anestesia Local/métodos , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/cirugía , Anciano , Radiculopatía/cirugía , Radiculopatía/etiología , Posicionamiento del Paciente/métodos , Adulto , Neuroendoscopía/métodos , Resultado del Tratamiento , Estenosis Espinal/cirugía , Endoscopía/métodosRESUMEN
For centuries, Hawaiians have gathered seaweed for food, medicine, and ceremonial purposes. Seaweed contains nutrients, but some varieties can accumulate toxic elements. We measured target macrominerals (Na, Mg, P, K, Ca), microminerals (B, V, Mn, Co, Cu, Zn, Mo), and nonessential/toxic elements (As, Sr, Cd, Sn, Hg, Pb, and U) in a sample of wild-collected and cultivated seaweeds from Hawai'i. The samples consisted of brown (Sargassum aquifolium, Sargassum echinocarpum), red (Gracilaria parvispora, Halymenia formosa, Halymenia hawaiiana), and green (Ulva ohnoi) seaweed. Elemental composition was determined by inductively coupled plasma (ICP)-atomic emission spectroscopy and ICP-mass spectrometry (MS). Speciation of As was conducted by using liquid chromatography-ICP-MS. S. echinocarpum per 80 g serving was high in Ca (~37% daily value [DV]), U. ohnoi was high in Mg (~40%DV), H. formosa was high in Fe (~40%DV), and G. parvispora was high in Mn (~128%DV). In this study, the highest amounts of toxic elements were observed in S. aquifolium and S. echinocarpum (27.6 mg inorganic As/kg fdw), G. parvispora (43.3 mg Pb/kg fdw) and H. formosa (46.6 mg Pb/kg fdw). These results indicate that although seaweeds from Hawai'i contain a variety of nutrients, some species can accumulate high amounts of toxic elements.
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PURPOSE: To compare outcomes of patients who underwent rotator cuff repair (RCR) with concomitant biceps tenodesis with those who underwent an isolated RCR. METHODS: Exclusion criteria included previous ipsilateral shoulder surgery, irreparable rotator cuff tears, rotator cuff arthropathy, calcific tendinitis, adhesive capsulitis requiring a capsular release, or advanced osteoarthritis of the glenohumeral joint. Patients were indicated for biceps tenodesis if they had any degree of tendon tearing, moderate-to-severe tenosynovitis, instability, or a significant degenerative SLAP tear. Primary outcome measures included American Shoulder and Elbow Surgeons score, Simple Shoulder Test, EuroQoL 5-Dimension 5-Level visual analog scale, EuroQoL 5-Dimension 5-Level, and a site-specific questionnaire, which focused on surgical expectations, satisfaction, and complications. Multivariate analysis of variance to analyze descriptive statistics and determine significant differences between the patient groups for subjective and objective outcome measures were performed. RESULTS: There were no significant differences for pain/visual analog scale (0.34 ± 0.09 vs 0.47 ± 0.09, P = .31), American Shoulder and Elbow Surgeons score (96.69 ± 0.87 vs 94.44 ± 0.91, P = .07), and Simple Shoulder Test (11.42 ± 0.17 vs 10.95 ± 0.18, P = .06) between the RCR with concomitant biceps tenodesis and isolated RCR at a minimum of 2 years' postoperatively. This is despite the RCR with concomitant biceps tenodesis group having significantly larger rotator cuff tears (4.25 ± 0.30 cm2 vs 2.80 ± 0.32 cm2, P = .001) than the isolated RCR group. CONCLUSIONS: This study revealed that concomitant biceps tenodesis does not compromise outcomes when compared with an isolated RCR at 2-year follow-up, despite this group having larger rotator cuff tears. LEVEL OF EVIDENCE: Level III, retrospective case study.
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Metastructures, artificial arrangements of micro/macrostructures, possess unique properties and are of significant interest in aerospace, stealth technology, and various other applications. Recent studies have focused on quasi-zero stiffness metastructures, providing an outstanding vibration isolation capability. However, existing methods are constrained to low preloads and lack the consideration of structural analysis, despite their intended use in practical structures. This study introduces metastructures with quasi-zero stiffness characteristics under high preloads by inducing local buckling. An optimization framework combining deep reinforcement learning and finite-element analysis is employed to derive an optimal model that considers both structural safety and quasi-zero stiffness characteristics. To validate the optimization results, quasi-zero stiffness metastructures are fabricated via 3D printing, and compression and vibration experiments are conducted. The fabricated metastructures exhibit quasi-zero stiffness characteristics under a high target preload along with outstanding vibration reduction performance, even in the low-frequency range.
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Background: Lung transplant surgery creates surgical pulmonary vein isolation (PVI) as a routine part of the procedure. However, many patients with pretransplant atrial fibrillation continue to have atrial fibrillation at 1 y. We hypothesized that the addition of electrical PVI and left atrial appendage isolation/ligation (LAL) to the lung transplant procedure restores sinus rhythm at 1 y in patients with pretransplant atrial fibrillation. Methods: We retrospectively reviewed all adult lung transplant recipients at the University of California Los Angeles from April 2006 to August 2021. All patients with pretransplant atrial fibrillation underwent concomitant PVI/LAL and were compared with lung transplant recipients without preoperative atrial fibrillation. In-hospital outcomes; 1-y survival; and the incidence of stroke, cardiac readmissions, repeat ablations, and sinus rhythm (composite endpoint) were examined at 1 y for the PVI/LAL cohort. Results: Sixty-one lung transplant recipients with pretransplant atrial fibrillation underwent concomitant PVI/LAL. No patient in the PVI/LAL cohort required cardiac-related readmission or catheter ablation for atrial fibrillation within 1 y of transplantation. Freedom from the composite endpoint of death, stroke, cardiac readmission, and repeat ablation for atrial fibrillation at 1 y was 85% (95% confidence interval, 73%-92%) for lung transplant recipients treated with PVI/LAL. Conclusions: The addition of PVI/LAI to the lung transplant operation in patients with pretransplant atrial fibrillation was safe and effective in maintaining sinus rhythm and baseline risk of stroke at 1 y.
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Monocytes are actively recruited to sites of infection and produce the potent proinflammatory cytokine IL-1ß. We previously showed that IL-1ß release during Toxoplasma gondii infection of primary human monocytes requires the NLRP3 inflammasome and caspase-1 but is independent of gasdermin D and pyroptosis. To investigate mechanisms of IL-1ß release, we generated caspase-1, -4, -5, or -8 knockout (KO) THP-1 monocytic cells. Genetic ablation of caspase-1 or -8, but not caspase-4 or -5, decreased IL-1ß release during T. gondii infection without affecting cell death. In contrast, TNF-α and IL-6 secretion were unperturbed in caspase-8 KO cells during T. gondii infection. Dual pharmacological inhibition of caspase-8 and RIPK1 in primary monocytes also decreased IL-1ß release without affecting cell viability or parasite infection. Caspase-8 was also required for the release of active caspase-1 from T. gondii-infected cells and for IL-1ß release during infection with the related apicomplexan parasite Neospora caninum. Surprisingly, caspase-8 deficiency did not impair synthesis or cleavage of pro-IL-1ß, but resulted in the retention of mature IL-1ß within cells. Generation of gasdermin E KO and ATG7 KO THP-1 cells revealed that the release of IL-1ß was not dependent on gasdermin E or ATG7. Collectively, our data indicate that during T. gondii Infection of human monocytes, caspase-8 functions in a novel gasdermin-independent mechanism controlling IL-1ß release from viable cells. This study expands on the molecular pathways that promote IL-1ß in human immune cells and provides evidence of a role for caspase-8 in the mechanism of IL-1ß release during infection.
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Caspasa 8 , Interleucina-1beta , Toxoplasma , Toxoplasmosis , Humanos , Caspasa 1/metabolismo , Caspasa 8/metabolismo , Gasderminas , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Monocitos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Toxoplasmosis/metabolismoRESUMEN
Prioritizing disease-critical cell types by integrating genome-wide association studies (GWAS) with functional data is a fundamental goal. Single-cell chromatin accessibility (scATAC-seq) and gene expression (scRNA-seq) have characterized cell types at high resolution, and studies integrating GWAS with scRNA-seq have shown promise, but studies integrating GWAS with scATAC-seq have been limited. Here, we identify disease-critical fetal and adult brain cell types by integrating GWAS summary statistics from 28 brain-related diseases/traits (average N = 298 K) with 3.2 million scATAC-seq and scRNA-seq profiles from 83 cell types. We identified disease-critical fetal (respectively adult) brain cell types for 22 (respectively 23) of 28 traits using scATAC-seq, and for 8 (respectively 17) of 28 traits using scRNA-seq. Significant scATAC-seq enrichments included fetal photoreceptor cells for major depressive disorder, fetal ganglion cells for BMI, fetal astrocytes for ADHD, and adult VGLUT2 excitatory neurons for schizophrenia. Our findings improve our understanding of brain-related diseases/traits and inform future analyses.
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Secuenciación de Inmunoprecipitación de Cromatina , Trastorno Depresivo Mayor , Humanos , RNA-Seq , Estudio de Asociación del Genoma Completo , Cromatina/genética , Encéfalo , Análisis de la Célula IndividualRESUMEN
INTRODUCTION: Subsolid nodules or those located deep in lung parenchyma are difficult to localize using minimally invasive thoracic surgery. While image-guided percutaneous needle localization has been performed, it is inconvenient and has potential complications. In this study, the role of chemical localization using robotic bronchoscopy to facilitate resection was evaluated. METHODS: Consecutive patients undergoing surgical resection for lung nodules between 8/2019-3/2022 were included. Patients with subsolid lung nodules, or small nodules deep in lung parenchyma that were deemed difficult to localize, were chemically localized (CL) using robotic bronchoscopy before resection. Clinico-demographic data were obtained retrospectively using a prospectively maintained database. RESULTS: Localization of lung nodules before resection was performed in 139 patients while 110 patients were not localized. Daily activity score was higher for localized patients. Nodules in the localized group were smaller (P < 0.001) and had similar solid:ground glass ratio. In the localized group, larger margins were observed, and no re-resection of the parenchymal margin was required. Twenty patients in the non-localized group required re-resection intraoperatively due to close pathological margins or inability to locate the nodule in the resected specimen. Operative time was a median of 10-15 min longer for localized patients, P < 0.001. Length of stay was shorter in the localized group (P < 0.05). CONCLUSIONS: Chemical localization of lung nodules using robotic bronchoscopy appears to be a safe and effective method of identifying the location of nodules with small size and less density and aids increased tumor margins intraoperatively.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Lesiones Precancerosas , Procedimientos Quirúrgicos Robotizados , Humanos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Broncoscopía/métodos , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Pulmón/patologíaRESUMEN
Due to the impact of nodal metastasis on colon cancer prognosis, adequate regional lymph node resection and accurate pathological evaluation are required. The ratio of metastatic to examined nodes may bring an additional prognostic value to the actual staging system. This study analyzes the identification of factors influencing a high lymph node yield and its impact on survival. The lymph node ratio was determined in patients with fewer than 12 or at least 12 evaluated nodes. The study included patients after radical colon cancer resection in UICC stages II and III. For the lymph node ratio (LNR) analysis, node-positive patients were divided into four categories: i.e., LNR 1 (<0.05), LNR 2 (≥0.05; <0.2), LNR 3 (≥0.2; <0.4), and LNR 4 (≥0.4), and classified into two groups: i.e., those with <12 and ≥12 evaluated nodes. The study was conducted on 7012 patients who met the set criteria and were included in the data analysis. The mean number of examined lymph nodes was 22.08 (SD 10.64, median 20). Among the study subjects, 94.5% had 12 or more nodes evaluated. These patients were more likely to be younger, women, with a lower ASA classification, pT3 and pN2 categories. Also, they had no risk factors and frequently had a right-sided tumor. In the multivariate analysis, a younger age, ASA classification of II and III, high pT and pN categories, absence of risk factors, and right-sided location remained independent predictors for a lymph node yield ≥12. The univariate survival analysis of the entire cohort demonstrated a better five-year overall survival (OS) in patients with at least 12 lymph nodes examined (68% vs. 63%, p = 0.027). The LNR groups showed a significant association with OS, reaching from 75.5% for LNR 1 to 33.1% for LNR 4 (p < 0.001) in the ≥12 cohort, and from 74.8% for LNR2 to 49.3% for LNR4 (p = 0.007) in the <12 cohort. This influence remained significant and independent in multivariate analyses. The hazard ratios ranged from 1.016 to 2.698 for patients with less than 12 nodes, and from 1.248 to 3.615 for those with at least 12 nodes. The LNR allowed for a more precise estimation of the OS compared with the pN classification system. The metastatic lymph node ratio is an independent predictor for survival and should be included in current staging and therapeutic decision-making processes.
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BACKGROUND: The purpose of the present study was to characterize the impact of the 2018 adult heart allocation policy change on waiting list and posttransplant outcomes of heart retransplantation in the United States. METHODS: All adults listed for heart retransplantation from May 2015 to June 2022 were identified using the United Network for Organ Sharing database. Patients were stratified into eras (era 1 and era 2) based on the heart allocation change on October 18, 2018. Competing risks regressions and Cox proportional hazards models were used to assess differences across eras in waiting list outcomes and 1-year posttransplant survival, respectively. RESULTS: The analysis included 356 repeat heart transplant recipients, with 207 (58%) receiving retransplantation during era 2. Patients who received a retransplant in era 2 were more commonly bridged with extracorporeal membrane oxygenation (21% vs 8%, P < .01) and intra-aortic balloon pump (29% vs 13%, P < .001) and had a lower likelihood of death/deterioration on the waiting list (subdistribution hazard ratio, 0.52; 95% CI, 0.33-0.82) compared with those in era 1. Rates of 30-day mortality (7% vs 7%, P = .99) and 1-year survival (82% vs 87%, P = .27) were not significantly different among retransplantation recipients across eras. After adjustment, retransplantation in era 2 was not associated with an increased hazard of mortality (adjusted hazard ratio, 1.13; 95% CI, 0.55-2.30). The gap in 1-year mortality between primary transplant and retransplant recipients increased from era 1 to 2. CONCLUSIONS: Heart retransplantation candidates have experienced improved waiting list outcomes after the 2018 adult heart allocation policy, without significant changes to posttransplant survival.
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Trasplante de Corazón , Adulto , Humanos , Estados Unidos/epidemiología , Reoperación , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Factores de Tiempo , Listas de EsperaRESUMEN
BACKGROUND: The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing-positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and midterm outcomes of lung transplant recipients of HCV NAT+ donor allografts. METHODS: All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by 1 year, early (30-day and in-hospital) mortality, and both 1- and 3-year survival, were compared between matched groups. RESULTS: A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%) and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, p < 0.001), more often female (44% vs 39%, p < 0.01), and more commonly died due to drug intoxication (56% vs 15%, p < 0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, p = 0.69) and female gender (43% vs 39%, p = 0.15) but had lower lung allocation scores (38 vs 41, p < 0.001) compared to others. Rates of acute rejection (13% vs 17%, p = 0.09), early mortality (30-day: 2% vs 1%, p = 0.59, in-hospital: 3% vs 4%, p = 0.38), as well as 1-year (90% vs 92%, p = 0.29) and 3-year survival (69% vs 75%, p = 0.13) were not significantly different between matched groups. CONCLUSIONS: Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality, and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.
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Hepatitis C , Trasplante de Pulmón , Adulto , Humanos , Femenino , Persona de Mediana Edad , Hepacivirus , Donantes de Tejidos , PulmónRESUMEN
Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.
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Trasplante de Pulmón , Disfunción Primaria del Injerto , Humanos , Disfunción Primaria del Injerto/etiología , Complemento C4b , Estudios Retrospectivos , Pulmón , Proteínas del Sistema Complemento , Trasplante de Pulmón/efectos adversos , Aloinjertos , Rechazo de Injerto/etiología , Rechazo de Injerto/patologíaRESUMEN
BACKGROUND: Given resource constraints during the coronavirus disease 2019 pandemic, we explored whether minimally invasive anatomic lung resections for early-stage lung cancer could undergo rapid discharge. METHODS: All patients with clinical stage I-II non-small cell lung cancer from September 2019 to June 2022 who underwent minimally invasive anatomic lung resection at a single institution were included. Patients discharged without a chest tube <18 hours after operation, meeting preset criteria, were considered rapid discharge. Demographics, comorbidities, operative details, and 30-day outcomes were compared between rapid discharge patients and nonrapid discharge "control" patients. Multivariable logistic regression was performed for predictors of nonrapid discharge. RESULTS: Overall, 430 patients underwent resection (200 lobectomies and 230 segmentectomies); 162 patients (37%) underwent rapid discharge and 268 patients (63%) were controls. The rapid discharge group was younger (66.5 vs 70.0 years; P < .001), was assigned to lower American Society of Anesthesiologists class (P = .02), had more segmentectomies than lobectomies (P = .003), and had smaller tumors (P < .001). There were no differences between groups in distance from home to hospital (P = .335) or readmission rates (P = .39). Increasing age had higher odds for nonrapid discharge (odds ratio, 1.04; 95% CI, 1.02-1.07), whereas segmentectomy had decreased odds (odds ratio, 0.46; 95% CI, 0.28-0.75). CONCLUSIONS: Approximately 37% of the patients underwent rapid discharge after operation with similar readmission rate to controls. Increasing age had higher odds for nonrapid discharge; segmentectomy was likely to lead to rapid discharge. Consideration of rapid discharge minimally invasive lung resection for early-stage lung cancer can result in significant reduction in inpatient resources without adverse patient outcomes.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/etiología , Alta del Paciente , Procedimientos Quirúrgicos Ambulatorios , Neumonectomía/efectos adversos , Pulmón/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Ex-situ lung perfusion (ESLP) can be used to assess and rehabilitate donor lungs, potentially expanding the donor pool. We examined the characteristics and outcomes of lung transplants performed with ESLP in the United States. METHODS: Retrospective review of the United Network for Organ Sharing registry of primary adult lung transplant recipients from February 28, 2018, to June 30, 2021, was performed, comparing baseline characteristics, in-hospital outcomes, and 1-year survival of ESLP vs no ESLP lung transplants. RESULTS: Of 8204 lung transplants, 426 (5.2%) were performed with ESLP. ESLP donors were older, more donation after circulatory death (DCD), and had lower PaO2:FiO2 (P:F) ratios. Recipients had lower lung allocation scores. ESLP lungs traveled further, had longer preservation times, and were more likely double lung transplants. Reintubation rates, extracorporeal membrane oxygenation at 72 hours, and hospital length of stay were greater in the ESLP group. On multivariable analysis, ESLP was not an independent predictor of 1-year survival. However, further analysis showed that DCD lungs managed on ESLP had worse 1-year survival compared to DCD lungs preserved with standard cold storage or with donation after brain death donor lungs. CONCLUSIONS: ESLP is used in a small percentage of lung transplants in the US and is not independently associated with 1-year survival. ESLP combined with DCD lungs, however, is associated with worse 1-year survival and warrants further investigation.