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Objective: Implementation and continuing optimization of enhanced recovery protocol after thoracic surgery results in significant improvement of postoperative outcomes. We observed a 10-fold increase in the rate of postoperative day (POD) 1 discharges following robotic thoracoscopic anatomic resections over time. We aimed to determine factors associated with safe POD1 discharges. Methods: We performed a retrospective analysis of a prospectively maintained database of robotic anatomic pulmonary resections between July 1, 2012, and June 30, 2022, with patients of the last 2.5 years forming the basis of this study. Data collected included demographics, insurance types, Area Deprivation Index (indicator of poverty), and operative and postoperative variables including length of stay, opioid use, daily pain levels, readmissions, and outpatient interventions. Factors associated with POD1 were analyzed using a logistic regression module. Result: In total, 279 patients met inclusion criteria (91 POD1 discharges, 32.6%; none discharged with a pleural catheter). There was neither an increase of postdischarge interventions for pleural complications nor readmission in early discharge patients. After adjusting for relevant factors, younger age, right middle lobectomy, lower opioid use on POD1, operating room finish before 4 PM, and low Area Deprivation Index were significantly associated with POD1 discharge. A subanalysis of 49 patients, who could have been discharged on POD1, identified hypoxemia requiring home oxygen, atrial fibrillation, and poorly controlled pain being common mitigatable clinical factors delaying POD1 discharge. Conclusions: Safe POD1 discharge following robotic thoracoscopic anatomic resection was achieved in 32% of cases. Identification of positive and negative factors affecting early discharge provides guidance for further modifications to increase the number of POD1 discharges.

Objectives: Textbook oncological outcome (TOO) is a composite metric for surgical outcomes, including non–small cell lung cancer (NSCLC). We hypothesized that social determinants of health (SDH) can affect both the attainment of TOO and the overall survival (OS) in surgically resected NSCLC patients with pathological nodal disease. Methods: We queried the National Cancer Database (2010-2017) for preoperative therapy-naïve lobectomies for NSCLC with tumor size

Objectives: Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control and have been associated with decreased opioid requirements. We investigated the impact of continual ERATS refinement on the incidence of opioid-free discharge. Methods: We retrospectively analyzed our prospectively maintained institutional database for elective, opioid-naive robotic thoracoscopic procedures. Demographics, operative outcomes, postoperative opioid dispensed (morphine milligram equivalent), and opioid discharge status were collected. Our primary outcome of interest was factors associated with opioid-free discharge; our secondary objective was to determine the incidence of new persistent opioid users. Results: In total, 466 patients from our optimized ERATS protocol were included; 309 (66%) were discharged without opioids. However, 34 (11%) of patients discharged without opioids required a prescription postdischarge. Conversely, 7 of 157 patients (11%), never filled their opioid prescriptions given at discharge. Factors associated with opioid-free discharges were nonanatomic resections, mediastinal procedures, minimal pain, and lack of opioid usage on the day of discharge. More importantly, 3.2% of opioid-free discharge patients became new persistent opioid users versus 10.8% of patients filling opioid prescriptions after discharges (P = .0013). Finally, only 2.3% of opioid-naive patients of the entire cohort became chronic opioid users; there was no difference in the incidence of chronic use by opioid discharge status. Conclusions: Optimized opioid-sparing ERATS protocols are highly effective in reducing opioid prescription on the day of discharge. We observed a very low rate of new persistent or chronic opioid use in our cohort, further highlighting the role ERATS protocols in combating the opioid epidemic.

Objective: In this study we aimed to determine the effect of the COVID-19 pandemic on the delivery of care for thoracic surgical patients at an urban medical center. Methods: A retrospective analysis of all thoracic surgical cases from May 1, 2019, to December 31, 2020, was conducted. Demographic characteristics, preoperative surgical indications, procedures, final pathologic diagnoses, and perioperative outcomes were recorded. A census of operative cases, relevant ancillary services, and outpatient thoracic clinics were obtained from our institutional database. Results: Six hundred nineteen cases were included in this study (329 pre-COVID-19 and 290 COVID-19, representing an 11.8% reduction). There were no differences in type of thoracic procedures or perioperative outcomes among the 2 cohorts. Prolonged reduction of thoracic surgical cases (50% of baseline) during the first half of the COVID-19 period was followed by a resurgence of surgical volumes to 110% of baseline in the second half. A similar incidence of cases were performed for oncologic indications during the first half whereas more benign cases were performed in the second half, coinciding with the launch of our robotic foregut surgery program. After undergoing surgery during the pandemic, none of our patients reported COVID-19 symptoms within 14 days of discharge. Conclusions: During the initial surge of COVID-19, while there was temporary closure of operative services, our health care system continued to provide safe care for thoracic surgery patients, particularly those with oncologic indications. Since phased reopening, we have experienced a rebound of surgical volume and case mix, ultimately mitigating the initial negative effect of the pandemic on delivery of thoracic surgical care.

Objectives: Our Enhanced Recovery After Thoracic Surgery protocol was implemented on February 1, 2018, and firmly established 7 months later. We instituted protocol modifications on January 1, 2020, aiming to further reduce postoperative opioid consumption. We sought to evaluate the influence of such efforts on clinical outcomes and the use of both schedule II and schedule IV opioids following robotic thoracoscopic procedures. Methods: A retrospective study of patients undergoing elective robotic procedures between September 1, 2018, and December 31, 2020, was conducted. Essential components of pain management in the original protocol included nonopioid analgesics, intercostal nerve blocks with long-acting liposomal bupivacaine diluted with normal saline, and opioids (ie, scheduled tramadol administration and as-needed schedule II narcotics). Protocol optimization included replacing saline diluent with 0.25% bupivacaine and switching tramadol to as needed, keeping other aspects unchanged. Demographic characteristics, type of robotic procedures, postoperative outcomes, and in-hospital and postdischarge opioids prescribed (ie, milligrams of morphine equivalent [MME]) were extracted from electronic medical records. Results: Three hundred twenty-four patients met the inclusion criteria (159 in the original and 183 in the optimized protocol). There was no difference in postoperative outcomes or acute postoperative pain; there was a significant reduction of in-hospital and postdischarge opioid requirements in the optimized cohort. For anatomic resections: mean, 60.0 MME (range, 0-60.0 MME) versus mean, 105.0 MME (range, 60.0-150.0 MME), and other procedures: mean, 0 MME (range, 0-60 MME) versus mean, 140.0 (range, 60.0-150.0 MME) (P

Cancer cells develop protective adaptations against oxidative DNA damage, providing a strong rationale for targeting DNA repair proteins. There has been a high degree of recent interest in inhibiting the mammalian Nudix pyrophosphatase MutT Homolog 1 (MTH1). MTH1 degrades 8-oxo-dGTP, thus limiting its incorporation into genomic DNA. MTH1 inhibition has variously been shown to induce genomic 8-oxo-dG elevation, genotoxic strand breaks in p53-functional cells, and tumor-inhibitory outcomes. Genomically incorporated 8-oxo-dG is excised by the base excision repair enzyme, 8-oxo-dG glycosylase 1 (OGG1). Thus, OGG1 inhibitors have been developed with the idea that their combination with MTH1 inhibitors will have anti-tumor effects by increasing genomic oxidative DNA damage. However, contradictory to this idea, we found that human lung adenocarcinoma with low OGG1 and MTH1 were robustly represented in patient datasets. Furthermore, OGG1 co-depletion mitigated the extent of DNA strand breaks and cellular senescence in MTH1-depleted p53-wildtype lung adenocarcinoma cells. Similarly, shMTH1-transduced cells were less sensitive to the OGG1 inhibitor, SU0268, than shGFP-transduced counterparts. Although the dual OGG1/MTH1 inhibitor, SU0383, induced greater cytotoxicity than equivalent combined or single doses of its parent scaffold MTH1 and OGG1 inhibitors, IACS-4759 and SU0268, this effect was only observed at the highest concentration assessed. Collectively, using both genetic depletion as well as small molecule inhibitors, our findings suggest that OGG1/MTH1 co-inhibition is unlikely to yield significant tumor-suppressive benefit. Instead such co-inhibition may exert tumor-protective effects by preventing base excision repair-induced DNA nicks and p53 induction, thus potentially conferring a survival advantage to the treated tumors.

Background: EBUS-TBNA is an integral tool in the diagnosis and staging of lung cancer and other diseases involving mediastinal lymphadenopathy. Most studies attesting to the performance of EBUS-TBNA are prospective analyses performed under strict protocols. The objective of our study was to compare the accuracy of EBUS-TBNA to surgery in diagnosing hilar and mediastinal pathologies in a tertiary hospital, staffed by pulmonologists with and without formal interventional pulmonary training.Methods: We retrospectively analyzed subjects who underwent EBUS-TBNA followed by a confirmatory surgical procedure from January 2012 to December 2018. The primary outcome was to evaluate the accuracy of EBUS-TBNA in the diagnosis of all mediastinal disease. Secondary analyses determined the accuracy of EBUS-TBNA in cancer, NSCLC, and non-malignant lesions individually.Results: One hundred and forty-three subjects had an EBUS-TBNA procedure followed by surgery. EBUS-TBNA for all pathologies had an accuracy of 81.2% (CI 95% 73.8–87.4) and sensitivity of 55.1% (CI 95% 41.5–68.3). The accuracy and sensitivity of individual groups were: cancer (81.7, 48.8%), NSCLC (84, 48.3%), and non-malignancy (78.9, 60%). The NSCLC group had 15 false negatives and 5 (33.3%) of them were due to non-sampling of EBUS accessible nodes. Missed sampling led to a change in the final staging in 8.6% of NSCLC subjects.Conclusion: The accuracy of EBUS-TBNA across all groups was comparable to those reported previously. However, the sensitivity was comparatively lower. This was primarily due to the large number of EBUS-TBNA accessible lymph nodes that were not sampled. This data highlights the need for guidelines outlining the best sampling approach and lymph node selection.

Inhibitors of histone deacetylases have been shown to enhance the sensitivity of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand TRAIL-mediated cytotoxicity. Valproic acid (VA), a commonly used antiepileptic agent whose pharmacokinetics and toxicity profiles are well described, is a histone deacetylase inhibitor. This project aims to evaluate if VA can potentiate Apo2L/TRAIL-mediated cytotoxicity in cultured thoracic cancer cells and to elucidate the underlying molecular mechanism responsible for this effect. VA sensitized cultured thoracic cancer cells to Apo2L/TRAIL, as indicated by a 4-fold to a >20-fold reduction of Apo2L/TRAIL IC50 values in combination-treated cells. Although VA (0.5–5 mM) or Apo2L/TRAIL (20 ng/ml) induced less than 20% cell death, VA + Apo2L/TRAIL combinations caused 60% to 90% apoptosis of cancer cells. Moreover, substantial activation of caspases 8, 9, and 3, which was observed only in cells treated with the drug combinations, was completely suppressed by BcI2 overexpression or by the caspase 9 inhibitor. Both the caspase 9 inhibitor and BcI2 completely abrogated the substantial cytotoxicity and apoptosis induced by this combination, thus highlighting the pivotal role of the type II pathway in this process. These findings provide a rationale for the development of VA and Apo2L/TRAIL combination as a novel molecular therapeutic regimen for thoracic cancers.

An outbreak of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) occurred in a college football team from August to September 2003. Eleven case-players were identified, and boils were the most common sign. Linemen had the highest attack rate (18%). Among 99 (93% of team) players with cultured specimens, 8 (8%) had positive MRSA nasal cultures. All available case-players’ MRSA isolates characterized had the community-associated pulsed-field type USA300. A case-control study found that sharing bars of soap and having preexisting cuts or abrasions were associated with infection. A carrier-control study found that having a locker near a teammate with an SSTI, sharing towels, and living on campus were associated with nasal carriage. Successful outbreak control measures included daily hexachlorophene showers and hygiene education.

Abstract Pulmonary interstitial emphysema (PIE) is a common problem in premature neonates with respiratory distress syndrome. This condition is often related to barotrauma caused by mechanical ventilation or continuous positive airway pressure applied to low birth weight neonates. The clinical diagnosis can be challenging. However, after proper diagnosis, several interventions are available for successful management. We describe an infant who developed severe PIE with recurrent pneumothoraces and development of a persistent bronchopleural fistula shortly after repair of a hypoplastic aortic arch and description of successful lobectomy with the assistance of extracorporeal support (ECMO).

The ability to rapidly detect biologically and environmentally significant metal ions such as zinc and mercury is important to study a number of important cellular and environmental processes. Hydrophilic bis(1,2,3-triazolyl)fluorene-based derivatives containing a 1,2,3-triazole-based recognition moiety were synthesized through Click chemistry and characterized by UV−vis absorption, fluorescence emission, and two-photon absorption as new fluorescence sensing probes, selective for Zn2橷 Hg2誉. The UV−vis absorption and fluorescence emission spectra of the complexes exhibited blue-shifted absorption and emission spectra upon chelation to Zn2橷 Hg2誉, resulting in ca. 2-fold enhancement in fluorescence. Fluorometric titration revealed that 1:2 and 1:3 ligand to metal complexes formed with binding constants of 108and 1016for Zn2橷 Hg2, respectively. The two-photon absorption cross sections for the probes and probe-metal ion complexes ranged from 200 to 350 GM at 800 nm. These novel fluorescent compounds may have potential as new metal ion sensors to probe cellular and biological environments. [ABSTRACT FROM AUTHOR]