Citations

ABSTRACT Background Treating Mycobacterium avium complex (MAC) infection pre‐lung transplant (LT) can be challenging to treat, given prolonged therapy and side effects. The impact of pre‐transplant MAC treatment on recurrence and outcomes post‐LT remains unclear, especially in patients with interstitial lung disease (ILD) who have a median survival of less than 2 years. Methods We performed a retrospective cohort study of adult LT patients at the Mayo Clinic who had positive MAC sputum cultures pre‐LT. The cohort was stratified and compared based on the type of treatment (complete, partial, or no treatment) for MAC pulmonary infection. The primary outcome was MAC recurrence post‐LT, and secondary outcomes were mortality, FEV‐1, and FVC at 1‐year post‐LT. Results Among the cohort of 47 patients, 9 (19.1%) were partially treated and 11 (23.4%) were completely treated for MAC infection pre‐LT. Post‐transplant MAC pulmonary infection recurrence occurred in eight (17%) of the total cohort, with four (14.8%) in the non‐treated, four (44.4%) in the partially‐treated, and none (0%) in the completely treated patients ( p = 0.026). There was no difference in mortality in patients who had MAC recurrence post‐transplantation (13% vs. 9.7%, p > 0.9) and those who were completely or partially treated, compared to non‐treated (0% vs. 13% vs. 13%, p > 0.9). The FEV1 and FVC at 1‐year post‐LT did not differ by the pre‐transplant treatment or post‐transplant MAC recurrence status. Conclusion The role of treatment for MAC infection pre‐transplant is questionable, especially in patients with diseases like ILD who may not have enough wait time to complete therapy.

Abstract Background: Expiratory central airway collapse (ECAC) is defined by excessive inward bulging of either posterior tracheobronchial membrane or anterolateral cartilage. ECAC commonly coexists with COPD, asthma, GERD, and obstructive sleep apnea. ECAC association with bronchiectasis is yet to be documented. Common conditions leading to bronchiectasis are obstructive lung diseases predisposing to recurrent infections, cystic fibrosis, COPD, or idiopathic. This study aims to evaluate the occurrence of bronchiectasis in patients with ECAC as the primary outcome and the correlation between the severity of bronchiectasis and the severity of ECAC as a secondary outcome. Methods: A retrospective single-center study evaluated patients diagnosed with ECAC using dynamic bronchoscopy in Mayo Clinic, Florida, from June 2019 to December 2020. Radiologists analyzed dynamic, or non-contrast chest computed tomography (CT) scans to evaluate the presence of bronchiectatic changes and the prevalence of bronchiectasis in this population. Bronchiectatic changes were documented using the Brody scoring system which recorded the bronchiectasis size, extent and tree in bud appearance in individual lobes. The final score had a range from 0 to 72. The bronchiectasis scores for individual lung lobes were analyzed to interpret distribution of bronchiectasis in ECAC population. The combined bronchiectasis scores of severe ECAC and non-severe ECAC cohorts were compared to assess if severe ECAC had higher bronchiectatic involvement. Results: Out of the 166 patients diagnosed with ECAC through dynamic bronchoscopy, 133 patients (80.1%) presented bronchiectatic changes in their CT scans. Of the 59 patients with severe ECAC, 51 patients (86.4%) were diagnosed with bronchiectasis. Of the 107 patients with non-severe ECAC, 82 (76.6 %) had bronchiectasis. The mean bronchiectasis scores are greater in right and left lower lobes, followed by middle lobes. The median values between severe and non-severe ECAC were 3 and 3 respectively with a p value of 0.34. The inter quartile range was 9 in severe ECAC group and 6 in non-severe ECAC (graph 1). Discussion: The outcomes of this study showed a significant presence of bronchiectatic changes in the ECAC population, implying the importance of evaluating for other pathologies. It can signify a pathological process similar to other pathologies which predispose to recurrent infections except for cystic fibrosis, which has an upper lobe involvement. The correlation of severity between ECAC and bronchiectasis requires more studies with a larger cohort for significant outcomes.

Importance Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery. Objective To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-guided vacuum assisted biopsy (VAB). Design, Setting, and Participants This single-arm, prospective, phase 2 nonrandomized clinical trial was conducted at 7 US medical centers and included women 40 years or older with cT1-2N0-1M0 ERBB2 -positive (formerly HER2 -positive) or triple-negative invasive BC who showed residual breast lesions after NST of less than 2 cm on imaging. Enrollment was from March 6, 2017, to November 9, 2021. Data analysis was from October to December 2024. Intervention Image-guided VAB of the tumor bed (9G with a minimum of 12 cores) was performed after standard NST. Patients with clinically node-negative disease at diagnosis and no residual cancer in the breast on post-NST VAB underwent whole-breast radiotherapy with a boost without breast or axillary surgery. Patients with initial documented nodal disease and a breast pCR on VAB underwent targeted axillary dissection, while those with residual cancer when undergoing VAB had standard breast and axillary surgery. Patients were monitored with physical examinations and mammography every 6 months. Main Outcome Measures The primary outcome was ipsilateral breast tumor recurrence. Results Fifty patients (median [IQR] age, 62 [55-77] years) were enrolled and underwent post-NST VAB. Twenty-nine (58%) and 21 (42%) patients had ERBB2 -positive and triple-negative invasive BC, respectively. Breast pCR on VAB was identified in 31 patients (62%; 95% CI, 47.2%-75.34%), and axillary pCR was identified among all 8 patients with initial nodal metastases and breast pCR on VAB who underwent targeted axillary dissection. At a median follow-up of 55.4 (IQR, 44.0-63.5) months, the ipsilateral breast tumor recurrence rate was 0%, and disease-free and overall survival rates were 100% for patients without breast surgery. Conclusions and Relevance The results of this nonrandomized clinical trial that reported preplanned 5-year outcomes suggest that omission of breast surgery in select patients after NST may be feasible, with no recurrences seen. More confirmatory studies are necessary before this new approach alters surgical practice. Trial Registration ClinicalTrials.gov Identifier: NCT02945579

AbstractExpiratory central airway collapse (ECAC) comprising excessive central airway collapse (EDAC) and tracheobronchomalacia. Treatment is challenging for severe cases that are not candidates for surgical management. We report a case of severe ECAC successfully managed with continuous positive airway pressure (CPAP) therapy. A 75‐year‐old female patient status post right pneumonectomy, presented with chronic cough. Dynamic bronchoscopy evaluation showed severe EDAC which improved with intraprocedural noninvasive positive pressure (NIPPV) therapy. Due to patients' comorbidities, she was not a candidate to surgical tracheobronchoplasty. Therefore, we attempted pneumatic stenting with long‐term CPAP therapy resulting in improvement of symptoms and functional capacity. The long‐term efficacy of pneumatic stenting has not been clearly established yet. Literature review of management of ECAC with NIPPV consist primarily of case reports and there is only one clinical trial being conducted to assess the efficacy of CPAP therapy in ECAC. While NIPPV arises as a sufficient alternative for management of severe ECAC, larger scale studies are needed to prove the real efficacy of NIPPV in this setting.

Abstract Rationale Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

Abstract Purpose: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here, we studied intratumoral and extratumoral relationships between adult patients with GBM and mice with brain tumors across the lifespan. Experimental Design: Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival. The commercial Tempus and Caris databases, as well as The Cancer Genome Atlas were profiled for gene expression, DNA methylation, and mutational changes with varying GBM patient age. In addition, gene expression analysis was performed on the extratumoral brain of younger and older adult mice with or without a brain tumor. The survival of young and old wild-type or transgenic (INK-ATTAC) mice with a brain tumor was evaluated after treatment with or without senolytics and/or immunotherapy. Results: Human patients with GBM ≥65 years of age had a significantly decreased survival compared with their younger counterparts. While the intra-GBM molecular profiles were similar between younger and older patients with GBM, non-tumor brain tissue had a significantly different gene expression profile between young and old mice with a brain tumor and the eradication of senescent cells improved immunotherapy-dependent survival of old but not young mice. Conclusions: This work suggests a potential benefit for combining senolytics with immunotherapy in older patients with GBM.

ImportancePatients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials.ObjectiveTo evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST).Design, Setting, and ParticipantsProspective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)–positive breast cancer with no pathologic evidence of residual disease following standard NST enrolled from March 6, 2017, to November 9, 2021. Validated PRO measures were administered at baseline and 6, 12, and 36 months post-radiotherapy. Data were analyzed from January to February 2023.InterventionsPRO measures included the Decision Regret Scale (DRS), Functional Assessment of Cancer Therapy—Lymphedema (FACT-B+4), and Breast Cancer Treatment Outcomes Scale (BCTOS).Main Outcomes and MeasuresChanges in PRO measure scores and subscores over time.ResultsAmong 31 patients, the median (IQR) age was 61 (56-66) years, 26 (84%) were White, and 26 (84%) were non-Hispanic. A total of 15 (48%) had triple-negative disease and 16 (52%) had ERBB2-positive disease. Decisional comfort was high at baseline (median [IQR] DRS score 10 [0-25] on a 0-100 scale, with higher scores indicating higher decisional regret) and significantly increased over time (median [IQR] DRS score at 36 months, 0 [0-20]; P < .001). HRQOL was relatively high at baseline (median [IQR] FACT-B composite score 121 [111-134] on a 0-148 scale, with higher scores indicating higher HRQOL) and significantly increased over time (median [IQR] FACT-B score at 36 months, 128 [116-137]; P = .04). Perceived differences between the affected breast and contralateral breast were minimal at baseline (median [IQR] BCTOS score 1.05 [1.00-1.23] on a 1-4 scale, with higher scores indicating greater differences) and increased significantly over time (median [IQR] BCTOS score at 36 months, 1.36 [1.18-1.64]; P < .001). At 36 months postradiotherapy, the cosmetic subscore was 0.45 points higher than baseline (95% CI, 0.16-0.74; P = .001), whereas function, pain, and edema subscores were not significantly different than baseline.Conclusions and RelevanceIn this nonrandomized phase 2 clinical trial, analysis of PROs demonstrated an overall positive experience for trial participants, with longitudinal improvements in decisional comfort and overall HRQOL over time and minimal lasting adverse effects of therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT02945579

AbstractRobotic‐assisted bronchoscopy (RAB) improves endoscopic diagnostic yield of solitary pulmonary nodules (SPN). Needle‐based confocal laser endomicroscopy (nCLE) is an emerging technology that allows high‐resolution, in‐vivo, real‐time assessment of living tissues at a cellular and subcellular level. Their combined use has been scarcely reported. We used them simultaneously in three patients with SPNs. For each, the nodule was evaluated with nCLE and sampled for pathology, followed by mediastinal staging. Median age was 77 years (67% male). Median nodule minimum size was 1.8 cm and maximum was 2.1 cm. nCLE detected abnormal patterns suggestive of malignancy for all nodules and pathology confirmed primary lung adenocarcinomas in two patients and lung primary squamous cell carcinoma in the other. The combined use of RAB with nCLE may potentially enhance the differentiation of malignant cells in real‐time and increase sample adequacy, accuracy, and diagnostic yield when biopsying a suspicious pulmonary lesion.

AbstractBackground and ObjectiveCurrently, computed tomography‐guided transthoracic biopsy (CTTB) is the most accurate diagnostic approach for pulmonary nodules suspected of malignancy. Traditional bronchoscopy has shown suboptimal diagnostic sensitivity, but the emergence of robotic‐assisted bronchoscopy (RAB) has the potential to improve diagnostic accuracy, maximize diagnostic yield and complete mediastinal and hilar staging in a single procedure. We aim to assess the efficacy and diagnostic performance of RAB compared to CTTB for diagnosing pulmonary nodules suspected of lung cancer.MethodsA multicenter retrospective review of consecutive patients who underwent RAB and CTTB for evaluating pulmonary nodules from January 2019 to March 2021 at Mayo Clinic Florida and Mayo Clinic Rochester, United States. Clinical and demographic information, nodule characteristics, outcomes and complications were compared between RAB and CTTB.ResultsA total of 225 patients were included: 113 in the RAB group and 112 in the CTTB group. Overall diagnostic yield was 87.6% for RAB and 88.4% for CTTB. For malignant disease, RAB had a sensitivity of 82.1% and a specificity of 100%, CTTB had a sensitivity of 88.5% and a specificity of 100%. Complication rate was significantly higher for CTTB compared to RAB (17% vs. 4.4%; p = 0.002).ConclusionRAB, when available, can be as accurate as CTTB for sampling pulmonary nodules with similar or reduced complications and should be considered as a means for nodule biopsy, particularly when mediastinal staging is also clinically warranted.