Citations

Abstract Rationale Inflammation is central to chronic obstructive pulmonary disease (COPD) pathogenesis but incompletely represented in COPD prognostic models. The neutrophil-to-lymphocyte ratio (NLR) is a readily available inflammatory biomarker. Objectives To explore the associations of NLR with smoking status, clinical features of COPD, and future adverse outcomes. Methods We analyzed NLR calculated from the complete blood count of participants who currently or formerly smoked (n = 2,624) and tobacco-naive control subjects (n = 187) in the SPIROMICS multicenter observational cohort study. We assessed the stability of NLR at 6 weeks and 1 year, the association with select blood biomarkers, and the impact of smoking on NLR and cell counts. We stratified participants by NLR quartiles to compare cross-sectional clinical features at enrollment, prospectively observed exacerbations at 1 year, and mortality during longitudinal follow up. Results Higher NLR quartiles were broadly associated with more severe clinical features of COPD. NLR values were repeatable at 6 weeks (intraclass correlation coefficient, 0.74) and 1 year (intraclass correlation coefficient, 0.62). The impact of smoking on NLR varied with the severity of airflow limitation, mediated by an interaction between smoking, forced expiratory volume in 1 second percent predicted, and neutrophil counts but not lymphocyte counts. The highest NLR quartile (>3.11) was associated with an increased risk of exacerbation over 1 year (adjusted odds ratio, 1.51; 95% confidence interval, 1.18, 1.92) and increased risk of mortality (adjusted hazard ratio, 1.41; 95% confidence interval, 1.20, 1.66) compared with quartiles 1–3. Conclusions Elevated NLR in stable COPD is a widely available biomarker associated with increased risk for exacerbation and death. The impact of cigarette smoking on NLR varies with disease severity.

ABSTRACT Background Flap complications following maxillectomy, reconstruction, and adjuvant proton beam therapy (PBT) for primary maxillary and sinonasal malignancies are not well described. Methods This retrospective cohort study included consecutive patients treated between 2016 and 2023 from a single‐institutional database. Results Thirteen patients were identified with a median follow‐up of 26 months. No immediate post‐operative complications occurred, with a median time between surgery and PBT of 61 days. Nine patients (69.2%) had high‐risk postoperative pathology and required 66+ Gy(RBE), including five (38.5%) with gross disease receiving 70 Gy(RBE). Flap necrosis and fistulization occurred in three patients (23.1%) following PBT (median time from PBT to complication, 112 days). Higher flap mean and minimum dose, flap volume receiving at least 66 Gy[RBE], and minimum dose to 50% flap volume were associated with complications. Conclusions Careful patient selection and planning strategies should be considered to mitigate flap complication risk following adjuvant PBT for high‐risk post‐operative pathology.

INTRODUCTION: The study aimed to develop consensus recommendations for the safe and appropriate use of liquid nitrogen spray cryotherapy in Barrett's esophagus and esophageal cancer. METHODS: Statements were initially formulated and grouped into categories of indications, training, preprocedure, intraprocedure, and postprocedure recommendations, frequency/timing of repeat procedures, and contraindications. Two investigators assessed the strength of the evidence for each statement using Grading of Recommendations Assessment, Development, and Evaluation methodology. Nineteen experts were invited to participate in a modified Delphi process. For statements that received >80% agreement, minor iterative edits were performed until there was unanimous consensus. If a threshold of 80% agreement was not reached, the statement was modified based on feedback and included in the next Delphi round. Statements were rejected if no consensus was reached after 3 rounds. RESULTS: After 3 Delphi rounds, 41 of 42 statements were accepted either in their original version (n = 11) or after modification based on expert input (n = 30). DISCUSSION: Through a modified Delphi process, we developed expert and evidence-based consensus recommendations to guide safe and appropriate use of liquid nitrogen spray cryotherapy in Barrett's esophagus and esophageal cancer.

Background: The impact of multiple substance use on the risk of pancreatitis remains underexplored. Objective: To systematically review peer-reviewed observational studies assessing the association of multiple substance use with the risk of acute pancreatitis (AP) or chronic pancreatitis (CP) in adults. Design: We conducted a systematic review informed by the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Data sources and methods: EMBASE, MEDLINE, and PsycINFO were searched up to March 2024. Reference lists of included studies were reviewed. From 5205 records identified, 181 relevant records were evaluated in full text. Studies evaluating the association of ⩾2 substances, including tobacco, alcohol, cannabis, and illicit substances, with AP or CP were included. Data were extracted by one reviewer, with quality control by a second reviewer. Quality assessments were independently conducted by two reviewers, with differences resolved by a third. Results: Of 11 included studies, 6 investigated AP as the outcome and 5 examined CP. Among AP studies, 5 comparing smoking and alcohol to alcohol-only use showed high heterogeneity ( I 2 = 90.9%), with relative risks (RRs) from 1.40 to 11.40. One study examining cannabis and alcohol versus alcohol found a lower risk of AP in cannabis users. Among CP studies, four comparing smoking and alcohol to alcohol-only use were heterogeneous ( I 2 = 81%) with odds ratios 1.21–31.50. Where examined, smoking increases the risk of AP and CP in a dose-dependent fashion. Heavy alcohol users demonstrated a significant increase in CP risk across all smoking categories in one study. Conclusion: Combined alcohol and tobacco use increases pancreatitis risk compared to single substance use, despite heterogeneity in RRs and exposure definitions. Evidence suggests a dose-dependent impact of smoking on pancreatitis risk when added to alcohol. Studies on the impact of a combination of other substance use on pancreatitis risk are needed. Trial registration (PROSPERO): CRD42024503677.

Abstract Rationale High-attenuation area (HAA) is a computed tomography (CT) tool that correlates with lung inflammation and fibrosis. Systemic molecular correlates of HAA (e.g., plasma proteins) may inform biological processes involved in interstitial lung disease. Objectives To identify plasma proteins that associate with HAA and correlate with a higher probability of developing new-onset fibrotic or subpleural interstitial lung abnormalities (ILAs). Methods Plasma protein levels were measured using a semiquantitative aptamer-based platform in MESA (the Multi-Ethnic Study of Atherosclerosis; N = 5,486) and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study; N = 1,781). Linear regression models identified HAA-associated proteins after adjustment for demographic and socioeconomic factors, CT scanner parameters, study center, and batch. Associations of HAA-related proteins with new-onset fibrotic or subpleural ILAs were examined in MESA participants with ILA assessments on full-lung CT 10 years later. Immunohistochemical staining of select proteins was performed in lung tissue from pulmonary fibrosis cases. Measurements and Main Results There were 75 proteins detected that were significantly associated with HAA in MESA and SPIROMICS. Gene Ontology analysis of these proteins identified processes involved in immune cell chemotaxis and cellular growth and apoptosis. Seven proteins were associated with a higher probability of new-onset fibrotic or subpleural ILAs in MESA, and two of these, junctional adhesion molecule-like protein and GTP cyclohydrolase 1 feedback regulatory protein, stained in areas of fibrosis in lung tissue from patients with interstitial lung disease. Conclusions Plasma proteins associated with more HAA are involved in immune and cellular processes and associate with new-onset fibrotic-subpleural ILA.

Abstract Context Data on diagnostic accuracy of dehydroepiandrosterone sulfate (DHEA-S) for mild autonomous cortisol secretion (MACS) and adrenal insufficiency (AI) are discrepant. Objective We conducted a systematic review and meta-analysis of published studies assessing the accuracy of DHEA-S in diagnosing MACS or AI. Methods From inception to January 8, 2024, we searched databases for original studies of at least 20 participants with MACS or AI. MACS was defined as postdexamethasone cortisol greater than 1.8 mcg/dL or postsurgical hypocortisolism. AI was defined by abnormal dynamic testing. QUADAS-2 was used to assess the risk of bias. Bivariate random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results Seven studies on DHEA-S accuracy in diagnosing MACS (574 patients with MACS, 830 referent individuals), and 2 studies on DHEA-S accuracy in diagnosing AI (52 patients with AI, 59 referent individuals) were included. A meta-analysis of studies using DHEA-S cutoff between 60 and 70 mcg/dL to diagnose MACS demonstrated a sensitivity of 82% (95% CI, 64%-93%) and a specificity of 82% (95% CI, 74%-88%). In the 2 studies evaluating DHEA-S in diagnosing AI, the reference standard was a 1-mcg cosyntropin stimulation test. The sensitivity of DHEA-S for diagnosing AI ranged from 70.3% to 86.7%, and the specificity was 87.1%. Most studies were at a moderate risk of bias. Conclusion Based on limited heterogeneous evidence, measurement of DHEA-S provides additional value in diagnosing MACS, as well as AI.

Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare, aggressive sarcomas, with 40% associated with neurofibromatosis type 1 (NF1). Surgical excision is the main treatment for localized disease; however, local recurrence (LR) remains high. Radiotherapy (RTx) is increasingly used to enhance local control in STS, but its use remains controversial due to the potential for increased major wound complications and an increased risk of secondary malignancies in NF1 patients. This study investigated the use and impact of RTx on local control in MPNSTs, particularly in the NF1 setting. Methods Surgically treated primary MPNSTs from 1988 to 2019 in the MONACO multicenter cohort were included. Differences in demographics, treatment, and RTx use between NF1 and non-NF1 cases were examined. Factors influencing RTx administration and LR were assessed via multivariable analyses. Results Among 499 patients (33.1% NF1), 143 (28.7%) experienced LRs. Radiotherapy was administered to 56.3% of patients (57.0% in the NF1 group), with 27.3% receiving neoadjuvant and 72.7% adjuvant RTx. RTx was administered significantly more often to high-grade and extremity tumors. While RTx did not affect overall survival, it reduced LR risk in sporadic cases (hazard ratio [HR] 0.530; 95% confidence interval [CI], 0.354–0.793) but not in the NF1 subgroup (HR 1.00; 95% CI, 0.545–1.85). In NF1 patients, a microscopically positive margin (R1) was the only risk factor for LR development (HR 2.1; 95% CI, 1.19–3.79). Conclusions RTx is frequently used in the treatment of MPNSTs, regardless of NF1 status. While it may affect the LR rate in sporadic cases, its impact on NF1 patients is less clear.

INTRODUCTION: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis. METHODS: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0–10 (n = 110) and 10–20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. Subjects were enrolled in the PROCEED study and classified symptomatic controls, acute/recurrent acute pancreatitis (AP/RAP), or CP. RESULTS: A significant main effect was detected in 10–20 minutes pancreas fluid ( P = 0.027) and plasma ( P = 0.046); post hoc testing showed PGE2 was lower in the AP/RAP group compared with symptomatic controls. There was also trend toward lower PGE2 in urine ( P = 0.062). To elucidate the active downstream pathways, calcitonin gene-related peptide, substance P, and matrix metalloproteinases (MMPs) 1, 2, 3, 7, 9, and 13 were measured in pancreas fluid. A significant difference between the 3 groups was detected for both MMP7 and MMP9. MMP7 was elevated in individuals with CP vs AP/RAP ( P = 0.012) for samples collected early but both time points for MMP9 ( P = 0.027, P = 0.002). DISCUSSION: While PGE2 is detectable in pancreas fluid, these data suggest that it may not be sensitive enough to distinguish between AP/RAP and CP. However, MMPs may distinguish between stages of pancreatitis and require further testing as potential diagnostic biomarkers.

Background: EUS-guided gastroenterostomy (EUS-GE) is an effective option for the management of gastric outlet obstruction (GOO). Due to the poor prognosis of patients undergoing it, data on its long-term adverse events (AE) is scarce. Herein, we describe a cohort of patients with gastro-entero-colic fistula (GECF) as a late AE of previously successful EUS-GE. Methods: Patients who developed a GECF after EUS-GE from 10 high-volume centers were analyzed. Information collected included demographic characteristics, indications, clinical and technical success rates, stent type and size, fistula characteristics, management, and outcomes. Results: Sixteen cases were identified. The mean interval from index EUS-GE to the diagnosis of GECF was 4 to 8 weeks. The most common cause of GOO was pancreatic adenocarcinoma (PDAC). The transverse colon was the most common site for the GECF (14 patients). A 20×10 mm lumen apposing metal stent (LAMS) was utilized in 10 patients. Endoscopic management with a variety of modalities was successful in 13 cases. Follow-up interval after endoscopic management of the fistula averaged 2 to 4 weeks. At the time of the manuscript elaboration, 10 patients had died, 5 were alive, and 1 was lost to follow-up. Conclusions: This is the first description of a cohort of patients with GECF after EUS-GE. The exact mechanisms leading to GECF in these cases are unknown. Possible explanations include inadvertent colon puncture during the index procedure and/or entrapment of mesocolon. More data is needed to further characterize this AE.