First-in-Human Intrathoracic Implantation of Multidrug-Eluting Microdevices for In Situ Chemotherapeutic Sensitivity Testing as Proof of Concept in Nonsmall Cell Lung Cancer.

OBJECTIVE: To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection. BACKGROUND: Adjuvant therapy has limited impact on postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens. METHODS: An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers. RESULTS: A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD. CONCLUSIONS: A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.

Finding the "True" N0 Cohort: Technical Aspects of Near-infrared Sentinel Lymph Node Mapping in Non-small Cell Lung Cancer.

OBJECTIVE: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification. BACKGROUND: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease. METHODS: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC. RESULTS: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1 mg compared to <1 mg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22). CONCLUSIONS: SLN(s) are more reliably identified with ICG dose ≥1 mg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.

Readability analysis of online resources related to lung cancer.

BACKGROUND: Patients seeking health information commonly use the Internet as the first source for material. Studies show that well-informed patients have increased involvement, satisfaction, and healthcare outcomes. As one-third of Americans have only basic or below basic health literacy, the National Institutes of Health and American Medical Association recommend patient-directed health resources be written at a sixth-grade reading level. This study evaluates the readability of commonly accessed online resources on lung cancer. METHODS: A search for "lung cancer" was performed using Google and Bing, and the top 10 websites were identified. Location services were disabled, and sponsored sites were excluded. Relevant articles (n = 109) with patient-directed content available directly from the main sites were downloaded. Readability was assessed using 10 established methods and analyzed with articles grouped by parent website. RESULTS: The average reading grade level across all sites was 11.2, with a range from 8.8 (New Fog Count) to 12.2 (Simple Measure of Gobbledygook). The average Flesch Reading Ease score was 52, corresponding with fairly difficult to read text. The readability varied when compared by individual website, ranging in grade level from 9.2 to 15.2. Only 10 articles (9%) were written below a sixth-grade level and these tended to discuss simpler topics. CONCLUSIONS: Patient-directed online information about lung cancer exceeds the recommended sixth-grade reading level. Readability varies between individual websites, allowing physicians to direct patients according to level of health literacy. Modifications to existing materials can significantly improve readability while maintaining content for patients with low health literacy.

A simplified minimally invasive technique for the treatment of venous lakes.

A simplified approach to treat venous lakes of the vermillion lip is presented. Our method involves the use of a 30 gauge hypodermic needle to deliver a low-powered, high-frequency electrical current from a hyfrecator power source into the venous lake lesion.

Effectiveness of an Online Preceptor Development Program Across Health Professions.

Introduction: An online Preceptor Development Program (PDP) was developed to meet the needs of geographically dispersed preceptors across health professions. We aimed to measure the audience, their engagement, and effectiveness of an online PDP developed and implemented amid the COVID-19 pandemic. Methods: The mixed methods study included survey and attendance data for live and asynchronous formats. T-tests compared overall session perception to self-reported session impact. Objective alignment and self-reported measures of impact were analyzed around Kirkpatrick's levels of reaction, learning, and behavior. Results: Participants engaged in live and/or asynchronous PDP sessions from various professions, specialties, and geographical locations. Quantitative findings indicated significant associations between overall session perception and knowledge (session 2), competence (sessions 1, 2), and performance (session 1). Objectives were met, and key learning takeaways were reported. While most participants indicated no barriers to implementation, two barriers identified were a lack of time and uninterested students. Conclusion: Participants were afforded flexibility and choice and likely benefitted in the areas of knowledge, competence, and behavior. This online PDP effectively addressed preceptor needs in common areas, including feedback. Future program development may include advisory group input and interactive learning opportunities.

Multi-institutional beta testing of a novel cervical esophagogastric anastomosis simulator.

Objective: A novel simulator developed to offer hands-on practice for the stapled side-to-side cervical esophagogastric anastomosis was tested previously in a single-center study that supported its value in surgical education. This multi-institutional trial was undertaken to evaluate validity evidence from 6 independent thoracic surgery residency programs. Methods: After a virtual session for simulation leaders, learners viewed a narrated video of the procedure and then alternated as surgeon or first assistant. Using an online survey, perceived value was measured across fidelity domains: physical attributes, realism of materials, realism of experience, value, and relevance. Objective assessment included time, number of sutures tearing, bubble test, and direct inspection. Comparison across programs was performed using the Kruskal-Wallis test. Results: Surveys were completed by 63 participants as surgeons (17 junior and 20 senior residents, 18 fellows, and 8 faculty). For 3 of 5 tasks, mean ratings of 4.35 to 4.44 correlated with "somewhat easy" to "very easy" to perform. The interrupted outer layer of the anastomosis rated lowest, suggesting this task was the most difficult. The simulator was rated as a highly valuable training tool. For the objective measurements of performance, "direct inspection" rated highest followed by "time." A total of 90.5% of participants rated the simulator as ready for use with only minor improvements. Conclusions: Results from this multi-institutional study suggest the cervical esophagogastric anastomosis simulator is a useful adjunct for training and assessment. Further research is needed to determine its value in assessing competence for independent operating and associations between improved measured performance and clinical outcomes.

When a segmentectomy is not a segmentectomy: Quality assurance audit and evaluation of required elements for an anatomic segmentectomy.

OBJECTIVE: The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability. METHODS: A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups. RESULTS: There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001) in nonanatomic segmentectomies for non-small cell lung cancer. CONCLUSIONS: Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.

Controlled apneic tracheostomy in patients with coronavirus disease 2019 (COVID-19).

OBJECTIVE: To develop a team-based institutional infrastructure for navigating management of a novel disease, to determine a safe and effective approach for performing tracheostomies in patients with COVID-19 respiratory failure, and to review outcomes of patients and health care personnel following implementation of this approach. METHODS: An interdisciplinary Task Force was constructed to develop innovative strategies for management of a novel disease. A single-institution, prospective, nonrandomized cohort study was then conducted on patients with coronavirus disease 2019 (COVID-19) respiratory failure who underwent tracheostomy using an induced bedside apneic technique at a tertiary care academic institution between April 27, 2020, and June 30, 2020. RESULTS: In total, 28 patients underwent tracheostomy with induced apnea. The median lowest procedural oxygen saturation was 95%. The median number of ventilated days following tracheostomy was 11. There were 3 mortalities (11%) due to sepsis and multiorgan failure; of 25 surviving patients, 100% were successfully discharged from the hospital and 76% are decannulated, with a median time of 26 days from tracheostomy to decannulation (range 12-57). There was no symptomatic disease transmission to health care personnel on the COVID-19 Tracheostomy Team. CONCLUSIONS: Patients with respiratory failure from COVID-19 disease may benefit from tracheostomy. This can be completed effectively and safely without viral transmission to health care personnel. Performing tracheostomies earlier in the course of disease may expedite patient recovery and improve intensive care unit resource use. The creation of a collaborative Task Force is an effective strategic approach for management of novel disease.

Progress in the Management of Early-Stage Non-Small Cell Lung Cancer in 2017.

The landscape of care for early-stage non-small cell lung cancer continues to evolve. While some of the developments do not seem as dramatic as what has occurred in advanced disease in recent years, there is a continuous improvement in our ability to diagnose disease earlier and more accurately. We have an increased understanding of the diversity of early-stage disease and how to better tailor treatments to make them more tolerable without impacting efficacy. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in the care of early-stage lung cancer patients have provided focused updates across multiple areas including screening, pathology, staging, surgical techniques and novel technologies, adjuvant therapy, radiotherapy, surveillance, disparities, and quality of life. The source for information includes large academic meetings, the published literature, or novel unpublished data from other international oncology assemblies.

Tip of iceberg: when unusual vision complaints with a normal examination prompt a closer look.

KEY CLINICAL MESSAGE: Nonorganic vision loss (NOVL) is a relatively common condition in pediatric patients. Prompt diagnosis can prevent costly, time-consuming, and frustrating workups. It is valuable for general practitioners and specialists alike to include NOVL in their differential when evaluating patients with visual complaints that are inconsistent with normal examination findings.

Central retinal vein occlusion after prolonged vomiting and repeated valsalva maneuvers associated with gastroenteritis and dehydration.

A 44-year-old man presented with central retinal vein occlusion (CRVO) in his right eye after prolonged vomiting and repeated Valsalva maneuvers associated with gastroenteritis and dehydration. He had no other pertinent medical history, and a subsequent systemic and hematologic evaluation was within normal limits. At initial diagnosis, his visual acuity was 20/70 due to diffuse cystoid macular edema (CME) and nonischemic CRVO. After six monthly intravitreal bevacizumab injections, his vision improved to 20/20 and the CME greatly improved. An episode of prolonged vomiting and repeated Valsalva maneuvers may be a potential risk factor for CRVO in younger patients.

Endophthalmitis caused by streptococcal species: clinical settings, microbiology, management, and outcomes.

PURPOSE: To report the clinical settings, antibiotic susceptibilities, and outcomes of endophthalmitis caused by Streptococcus species. DESIGN: Retrospective, observational case series. METHODS: Single-center study evaluating all patients with culture-positive endophthalmitis caused by Streptococcus species between January 1, 2000, and December 31, 2011. RESULTS: Study criteria were met by 63 patients. The most common clinical settings were bleb associated (n = 17; 27%), after intravitreal injection (n = 16; 25%), and after cataract surgery (n = 13; 21%). The isolates were Streptococcus viridans (n = 47; 71%), Streptococcus pneumoniae (n = 13; 21%), and ß-hemolytic Streptococci (n = 5; 8%). Sixty (95%) of 63 isolates were susceptible to vancomycin, 47 (98%) of 48 isolates were susceptible to ceftriaxone (third-generation cephalosporin), and 57 (93%) of 61 isolates were susceptible to levofloxacin (third-generation fluoroquinolone). Between the first and second half of the study, the minimal inhibitory concentration of antibiotics required to inhibit 90% of isolates increased by 1.5-fold for ceftriaxone and 2-fold for levofloxacin and remained the same for vancomycin. Initial treatment was vitreous tap (49; 78%) or pars plana vitrectomy (14; 22%); all received intravitreal antibiotics. Visual acuity outcomes were variable: best-corrected visual acuity was 20/400 or better in 16 (25%) patients and worse than 20/400 in 47 (75%) patients. Evisceration or enucleation was performed in 16 (25%) patients. CONCLUSIONS: Streptococcus isolates generally had high susceptibility rates to commonly used antibiotics. Higher antibiotic minimal inhibitory concentrations were required to inhibit 90% of isolates in vitro in the second half of the study period compared with the first half. Despite prompt treatment, most patients had poor outcomes.

Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury.

Acute kidney injury (AKI) is a major clinical problem in which a critical vascular, pathophysiological component is recognized. We demonstrated previously that mesenchymal stem cells (MSC), unlike fibroblasts, are significantly renoprotective after ischemia-reperfusion injury and concluded that this renoprotection is mediated primarily by paracrine mechanisms. In this study, we investigated whether MSC possess vasculoprotective activity that may contribute, at least in part, to an improved outcome after ischemia-reperfusion AKI. MSC-conditioned medium contains VEGF, HGF, and IGF-1 and augments aortic endothelial cell (EC) growth and survival, a response not observed with fibroblast-conditioned medium. MSC and EC share vasculotropic gene expression profiles, as both form capillary tubes in vitro on Matrigel alone or in cooperation without fusion. MSC undergo differentiation into an endothelial-like cell phenotype in culture and develop into vascular structures in vivo. Infused MSC were readily detected in the kidney early after reflow but were only rarely engrafted at 1 wk post-AKI. MSC attached in the renal microvascular circulation significantly decreased apoptosis of adjacent cells. Infusion of MSC immediately after reflow in severe ischemia-reperfusion AKI did not improve renal blood flow, renovascular resistance, or outer cortical blood flow. These data demonstrate that the unique vasculotropic, paracrine actions elicited by MSC play a significant renoprotective role after AKI, further demonstrating that cell therapy has promise as a novel intervention in AKI.

Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms.

Severe acute renal failure (ARF) remains a common, largely treatment-resistant clinical problem with disturbingly high mortality rates. Therefore, we tested whether administration of multipotent mesenchymal stem cells (MSC) to anesthetized rats with ischemia-reperfusion-induced ARF (40-min bilateral renal pedicle clamping) could improve the outcome through amelioration of inflammatory, vascular, and apoptotic/necrotic manifestations of ischemic kidney injury. Accordingly, intracarotid administration of MSC (approximately 10(6)/animal) either immediately or 24 h after renal ischemia resulted in significantly improved renal function, higher proliferative and lower apoptotic indexes, as well as lower renal injury and unchanged leukocyte infiltration scores. Such renoprotection was not obtained with syngeneic fibroblasts. Using in vivo two-photon laser confocal microscopy, fluorescence-labeled MSC were detected early after injection in glomeruli, and low numbers attached at microvasculature sites. However, within 3 days of administration, none of the administered MSC had differentiated into a tubular or endothelial cell phenotype. At 24 h after injury, expression of proinflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma, and inducible nitric oxide synthase was significantly reduced and that of anti-inflammatory IL-10 and bFGF, TGF-alpha, and Bcl-2 was highly upregulated in treated kidneys. We conclude that the early, highly significant renoprotection obtained with MSC is of considerable therapeutic promise for the cell-based management of clinical ARF. The beneficial effects of MSC are primarily mediated via complex paracrine actions and not by their differentiation into target cells, which, as such, appears to be a more protracted response that may become important in late-stage organ repair.