Most patients with non–small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)–induced cell death (NICD) of P2X7 receptor (P2X7R)–expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono–adenosine 5′-diphosphate (ADP)–ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R ⁺ CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R ⁺ CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon blockade of the NAD ⁺ -degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell–dependent manner. This was associated with increased infiltration of activated P2X7R ⁺ CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies.

In the modern era, minimally invasive surgery is rapidly evolving and even replacing conventional open techniques in many surgical fields. Thyroidectomy was not an exception, with the introduction of multiple endoscopic thyroidectomy techniques. Trans-oral endoscopic trans-vestibular thyroidectomy (TOT) is a novel technique with promising outcomes. We conducted this meta-analysis to compare surgical outcomes and learning curves for TOT and other endoscopic thyroidectomy techniques. A systematic review in PubMed, MEDLINE, and EMBASE databases was conducted searching for publications on TOT versus trans-axillary thyroidectomy (TAT). The primary endpoint was operative (OR) time. Secondary endpoints were number of harvested lymph nodes (LNs), estimated blood loss (EBL), recurrent laryngeal nerve (RLN) injury, hoarseness, seroma, infection, chyle leak, hypocalcemia, hospital length of stay (LOS), and Cost. We also investigated the learning curve for each technique. Leave-out-out analysis, meta-regression, and subgroup analysis were used. Random effect inverse variance method was utilized. Among 3820 retrieved studies, 15 studies (10 unmatched and 5 matched), with 2173 (TOT: 1024(47.12%) and TAT:1149(52.87%)) patients, met the inclusion criteria. The operative time and harvested L. Ns number were higher in TOT versus TAT (standard mean difference (SMD) = 0.72 [95%CI 0.07; 1.37], P = 0.029 and SMD = 0.32 [95%CI 0.02; 0.62], P = 0.036 respectively) while less EBL in TOT versus TAT (SMD = -0.26 [-0.43; -0.09], P = 0.0018). All other outcomes showed no significant difference between both groups. Weighted mean values for TOT and TAT were 158.03 vs 144.97 min for OR time, 6.33 vs 5.16 for harvested LNs, and $5,919.05 vs $6,253.79 for the cost. Statistical significance in learning curve development was noticed ranging between 6 and 15 annual cases. Trans-oral thyroidectomy is a safe and reliable technique with outcomes comparable to other endoscopic techniques. It provides better access to the central compartment with a more feasible LN dissection. Improvement in surgical outcomes is expected with growing learning curve and technique mastery.

Background: Anastomotic leak after esophagectomy carries important short- and long-term sequelae. The authors conducted a systematic review and meta-analysis to determine its association with surgical volume. Materials and methods: A systematic literature review was performed to identify all studies reporting on anastomotic leak after esophagectomy. Studies with less than 100 cases were excluded. The primary outcome was postesophagectomy anastomotic leak, while secondary outcomes were operative mortality overall and after anastomotic leak. Pooled event rates (PER) were calculated, and the association with annual esophagectomy volume by center was investigated. Results: Of the 3932 retrieved articles, 472 were included (n=177 566 patients). The PER of anastomotic leak was 8.91% [95% CI=8.32; 9.53%]. The PER of early mortality overall and after an anastomotic leak was 2.49% [95% CI=2.27; 2.74] and 11.39% [95% CI=9.66; 13.39], respectively. Centers with less than 37 annual esophagectomies had a higher leak rate compared to those with greater than or equal to 37 annual esophagectomies (9.58% vs. 8.34%; P=0.040). On meta-regression, surgical volume was inversely associated with the PER of esophageal leak and of early mortality. Conclusions: The frequency of anastomotic leaks after esophagectomy, perioperative, and leak associated mortality are inversely associated with esophagectomy volume.

Coping with the COIVD-19 global-pandemic major changes in healthcare and educational operational policies, mandates the implementation of alternative surgical curriculum objects (components) to replace some of the traditional face-to-face activities. The objective of the study is to review and discuss various alternative curriculum objects (components) that can be used to restructure conventional surgical training curricula during the Declared Healthcare Emergency surgery rotations. The goal is to identify and recommend effective alternative educational activities that are compliant with the new social physical distancing regulations. Various curricular components and objects were examined. The educational value of the curriculum objects is studied and analyzed in terms of feasibility, knowledge gain/learning effectiveness, the need for facilitation or feedback, and the evaluation. Several curriculum objects were proposed with description of their value and applications. The selected and proposed activities include scenario-based MCQ writing exercises, video-based surgical skills interactive training, online learning modules, virtual rounding, reflection assignments, surgical skills simulation training, research education, and medical education learning. Their educational value is described and scaled. There is urgent and challenging need for surgical training using additional alternative curriculum objects (components). Working with the available resources and experiences is crucial to maximize the learning outcomes. Distance (online) education and educational technology tools and concepts provide a spectrum of valuable educational activities. Further work and studies are needed to optimize their utility.