Protecting the non-operative lobe/s of the operative lung can reduce the pneumonia incidence after thoracoscopic lobectomy: a randomised controlled trial.

Lung isolation usually refers to the isolation of the operative from the non-operative lung without isolating the non-operative lobe(s) of the operative lung. We aimed to evaluate whether protecting the non-operative lobe of the operative lung using a double-bronchial blocker (DBB) with continuous positive airway pressure (CPAP) could reduce the incidence of postoperative pneumonia. Eighty patients were randomly divided into two groups (n = 40 each): the DBB with CPAP (Group DBB) and routine bronchial blocker (Group BB) groups. In Group DBB, a 7-Fr BB was placed in the middle bronchus of the right lung for right lung surgery and in the inferior lobar bronchus of the left lung for left lung surgery. Further, a 9-Fr BB was placed in the main bronchus of the operative lung. In Group BB, routine BB placement was performed on the main bronchus on the surgical side. The primary endpoint was the postoperative pneumonia incidence. Compared with Group BB, Group DBB had a significantly lower postoperative pneumonia incidence in the operative (27.5% vs 5%, P = 0.013) and non-operative lung (40% vs 15%) on postoperative day 1. Compared with routine BB use for thoracoscopic lobectomy, using the DBB technique to isolate the operative lobe from the non-operative lobe(s) of the operative lung and providing CPAP to the non-operative lobe(s) through a BB can reduce the incidence of postoperative pneumonia in the operative and non-operative lungs.

Effect of lung isolation with different airway devices on postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery: a propensity score-matched study.

BACKGROUND: Postoperative pneumonia is one of the common complications after video-assisted thoracoscopic surgery. There is no related study on the effect of lung isolation with different airway devices on postoperative pneumonia. Therefore, in this study, the propensity score matching method was used to retrospectively explore the effects of different lung isolation methods on postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery. METHODS: This is A single-center, retrospective, propensity score-matched study. The information of patients who underwent VATS in Weifang People 's Hospital from January 2020 to January 2021 was retrospectively included. The patients were divided into three groups according to the airway device used in thoracoscopic surgery: laryngeal mask combined with bronchial blocker group (LM + BB group), tracheal tube combined with bronchial blocker group (TT + BB group) and double-lumen endobronchial tube group (DLT group). The main outcome was the incidence of pneumonia within 7 days after surgery; the secondary outcome were hospitalization time and hospitalization expenses. Patients in the three groups were matched using propensity score matching (PSM) analysis. RESULTS: After propensity score matching analysis, there was no significant difference in the incidence of postoperative pneumonia and hospitalization time among the three groups (P > 0.05), but there was significant difference in hospitalization expenses among the three groups (P < 0.05). CONCLUSIONS: There was no significant difference in the effect of different intubation lung isolation methods on postoperative pneumonia in patients undergoing thoracoscopic surgery.

The development of a risk assessment tool for patients with postoperative pneumonia after gastrectomy for gastric cancer.

BACKGROUND: Although frail patients are known to experience increased postoperative complications, this is unclear for postoperative pneumonia (POP). We investigated associations between frailty and POP in patients with gastric cancer (GC) undergoing gastrectomy. METHODS: In this prospective study conducted between August 2016 and December 2022, we preoperatively assessed frailty in 341 patients with GC undergoing gastrectomy using a frailty index (FI). Patients were divided into high FI vs low FI groups to examine frailty and pneumonia rates after gastrectomy for GC. RESULTS: Of 327 patients, 18 (5.5%) experienced POP after gastrectomy. Multivariate analyses showed that a high FI and total or proximal gastrectomy (TG/PG) were independent risk factors for POP (high FI: odds ratio [OR], 5.00; 95% CI, 1.77-15.54; TG/PG: OR, 3.07; 95% CI, 1.09-8.78). The proportion of patients with POP was 2.4% in those with nonhigh FI and non-TG/PG, 5.3% in those with nonhigh FI and TG/PG, 7.1% in those with high FI and non-TG/PG, and 28.0% in those with high FI and TG/PG (P < .001). The area under the receiver operating characteristic curve for this risk assessment for predicting POP was 0.740. CONCLUSION: In patients with GC undergoing gastrectomy, POP was independently associated with preoperatively high FI and TG/PG. Our simple POP risk assessment method, which combines these factors, may effectively predict and prepare patients for POP.

The Relationship between the Duration of Surgery for Thoracoscopic Lobectomy and Postoperative Complications in Patients with Stage I Non-small Cell Lung Cancer.

OBJECTIVE: To investigate the relationship between the duration of surgery for thoracoscopic lobectomy and postoperative complications in patients with stage I non-small cell lung cancer (NSCLC). METHODS: The clinical data of patients who underwent thoracoscopic lobectomy in the Department of Cardiothoracic Surgery, Shaoxing Central Hospital from September 2018 to September 2023 were retrospectively analyzed. RESULTS: A total of 263 patients with thoracoscopic lobectomy were enrolled in this study. The duration of surgery was longer for patients with postoperative hospital stay >7 days, atrial fibrillation, postoperative pulmonary air leakage (>5 days), pleural effusion, or pneumonia compared to patients without corresponding complications, and the differences were statistically significant. Further regression analysis showed that prolonged duration of surgery was a risk factor for pneumonia, pleural effusion, atrial fibrillation, and postoperative hospital stay >7 days, and the predictive value of prolonged duration of surgery for the above complications was moderate. The results of chi-square tests showed that pneumonia, atelectasis, urinary tract infection, liver dysfunction, postoperative pulmonary air leakage (>5 days), pleural effusion, and atrial fibrillation were associated with postoperative hospital stay >7 days. CONCLUSION: Prolonged duration of surgery is a risk factor for complications such as pneumonia, pleural effusion, atrial fibrillation, and postoperative hospital stay >7 days.

A meta-analysis and trial sequential analysis of randomised controlled trials comparing nonoperative and operative management of chest trauma with multiple rib fractures.

BACKGROUND: Operative treatment of traumatic rib fractures for better outcomes remains under debate. Surgical stabilization of rib fractures has dramatically increased in the last decade. This study aimed to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) to assess the effectiveness and safety of operative treatment compared to conservative treatment in adult patients with traumatic multiple rib fractures. METHODS: A systematic literature review was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines. We searched MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials and used the Cochrane Risk-of-Bias 2 tool to evaluate methodological quality. Relative risks with 95% confidence interval (CI) were calculated for outcomes: all-cause mortality, pneumonia incidence, and number of mechanical ventilation days. Overall certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, with trial sequential analysis performed to establish implications for further research. RESULTS: From 719 records, we included nine RCTs, which recruited 862 patients. Patients were assigned to the operative group (received surgical stabilization of chest wall injury, n = 423) or control group (n = 439). All-cause mortality was not significantly different (RR = 0.53; 95% CI 0.21 to 1.38, P = 0.35, I2 = 11%) between the two groups. However, in the operative group, duration of mechanical ventilation (mean difference -4.62; 95% CI -7.64 to -1.60, P < 0.00001, I2 = 94%) and length of intensive care unit stay (mean difference -3.05; 95% CI -5.87 to -0.22; P < 0.00001, I2 = 96%) were significantly shorter, and pneumonia incidence (RR = 0.57; 95% CI 0.35 to 0.92; P = 0.02, I2 = 57%) was significantly lower. Trial sequential analysis for mortality indicated insufficient sample size for a definitive judgment. GRADE showed this meta-analysis to have very low to low confidence. CONCLUSION: Meta-analysis of large-scale trials showed that surgical stabilization of multiple rib fractures shortened the duration of mechanical ventilation and reduced the incidence of pneumonia but lacked clear evidence for improvement of mortality compared to conservative treatment. Trial sequential analysis suggested the need for more cases, and GRADE highlighted low certainty, emphasizing the necessity for further targeted RCTs, especially in mechanically ventilated patients. SYSTEMATIC REVIEW REGISTRATION: UMIN Clinical Trials Registry UMIN000049365.

Vaping-Dependent Pulmonary Inflammation Is Ca2+ Mediated and Potentially Sex Specific.

Here we use the SCIREQ InExpose system to simulate a biologically relevant vaping model in mice to investigate the role of calcium signaling in vape-dependent pulmonary disease as well as to investigate if there is a gender-based difference of disease. Male and female mice were vaped with JUUL Menthol (3% nicotine) using the SCIREQ InExpose system for 2 weeks. Additionally, 2-APB, a known calcium signaling inhibitor, was administered as a prophylactic for lung disease and damage caused by vaping. After 2 weeks, mice were exposed to lipopolysaccharide (LPS) to mimic a bacterial infection. Post-infection (24 h), mice were sacrificed, and bronchoalveolar lavage fluid (BALF) and lungs were taken. Vaping primed the lungs for worsened disease burden after microbial challenge (LPS) for both males and females, though females presented increased neutrophilia and inflammatory cytokines post-vape compared to males, which was assessed by flow cytometry, and cytokine and histopathological analysis. This increased inflammatory burden was controlled by calcium signaling inhibition, suggesting that calcium dysregulation may play a role in lung injury caused by vaping in a gender-dependent manner.

The Impact of PM2.5 on Radiation-induced Pneumonitis in Patients With Breast Cancer.

BACKGROUND/AIM: Exposure to particulate matter (PM) air pollution is known to adversely affect respiratory disease, but no study has examined its effect on radiation-induced pneumonitis (RIP) in patients with breast cancer. PATIENTS AND METHODS: We conducted a retrospective review of 2,736 patients with breast cancer who received postoperative radiation therapy (RT) between 2017 and 2020 in a single institution. The distance between the PM measurement station and our institution was only 3.43 km. PM data, including PM2.5 and PM10, were retrieved from the open dataset in the official government database. RESULTS: Overall incidence rate of RIP was 1.74%. After adjusting for age, RT technique, regional irradiation, fractionation and boost, the average value of PM2.5 was significantly associated with a higher risk of RIP (p=0.047) when patients received ≥20 fractions of RT. Specifically, PM2.5 ≥35 (µg/m3) showed a significantly higher risk of RIP (p=0.019) in patients with ≥20 fractions of RT. CONCLUSION: This is the first study to reveal the association between PM2.5 and RIP in patients with breast cancer who received 20 fractions or more of postoperative RT. We demonstrated that high PM2.5 levels around the RT institution were associated with RIP, suggesting that reducing PM air pollution may be a modifiable risk factor.

Factors affecting duration of stay in the intensive care unit after coronary artery bypass surgery and its impact on in-hospital mortality: a retrospective study.

BACKGROUND: Different risk factors affect the intensive care unit (ICU) stay after cardiac surgery. This study aimed to evaluate these risk factors. PATIENTS AND METHODS: A retrospective analysis was conducted on clinical, operative, and outcome data from 1070 patients (mean age: 59 ± 9.8 years) who underwent isolated coronary bypass grafting CABG surgery with cardiopulmonary bypass. The outcome variable was prolonged length of stay LOS in the CICU stay (> 3 nights after CABG). RESULTS: Univariate predictors of prolonged ICU stays included a left atrial diameter of > 4 cm (P < 0.001),chronic obstructive airway disease COPD (P = 0.005), hypertension (P = 0.006), diabetes mellitus (P = 0.009), having coronary stents (P = 0.006), B-blockers use before surgery (either because the surgery was done on urgent or emergency basis or the patients have contraindication to B-blockers use) (P = 0.005), receiving blood transfusion during surgery (P = 0.001), post-operative acute kidney injury (AKI) (P < 0.001), prolonged inotropic support of > 12 h (P < 0.001), and ventilation support of > 12 h (P < 0.001), post-operative sepsis or pneumonia (P < 0.001), post-operative stroke/TIA (P = 0.001), sternal wound infection (P = 0.002), and postoperative atrial fibrillation POAF (P < 0.001). Multivariate regression revealed that patients with anleft atrial LA diameter of > 4 cm (AOR 2.531, P = 0.003), patients who did not take B-blockers before surgery (AOR 1.1 P = 0.011), patients on ventilation support > 12 h (AOR 3.931, P = < 0.001), patients who developed pneumonia (AOR 20.363, P = < 0.001), and patients who developed post-operative atrial fibrillation (AOR 30.683, P = < 0.001) were more likely to stay in the ICU for > 3 nights after CABG. CONCLUSION: Our results showed that LA diameter > 4 cm, patients who did not take beta-blockers before surgery, on ventilation support > 12 h, developed pneumonia post-operatively, and developed POAF were more likely to have stays lasting > 3 nights. Efforts should be directed toward reducing these postoperative complications to shorten the duration of CICU stay, thereby reducing costs and improving bed availability.

Readmission after enhanced recovery video-assisted thoracoscopic surgery wedge resection.

BACKGROUND: Despite the implementation of Enhanced Recovery After Surgery (ERAS) programs, surgical stress continues to influence postoperative rehabilitation, including the period after discharge. However, there is a lack of data available beyond the point of discharge following video-assisted thoracoscopic surgery (VATS) wedge resection. Therefore, the objective of this study is to investigate incidence and risk factors for readmissions after ERAS VATS wedge resection. METHODS: A retrospective analysis was performed on data from prospectively collected consecutive VATS wedge resections from June 2019 to June 2022. We evaluated main reasons related to wedge resection leading to 90-day readmission, early (occurring within 0-30 days postoperatively) and late readmission (occurring within 31-90 days postoperatively). To identify predictors for these readmissions, we utilized a logistic regression model for both univariable and multivariable analyses. RESULTS: A total of 850 patients (non-small cell lung cancer 21.5%, metastasis 44.7%, benign 31.9%, and other lung cancers 1.9%) were included for the final analysis. Median length of stay was 1 day (IQR 1-2). During the postoperative 90 days, 86 patients (10.1%) were readmitted mostly due to pneumonia and pneumothorax. Among the cohort, 66 patients (7.8%) had early readmissions primarily due to pneumothorax and pneumonia, while 27 patients (3.2%) experienced late readmissions mainly due to pneumonia, with 7 (0.8%) patients experiencing both early and late readmissions. Multivariable analysis demonstrated that male gender, pulmonary complications, and neurological complications were associated with readmission. CONCLUSIONS: Readmission after VATS wedge resection remains significant despite an optimal ERAS program, with pneumonia and pneumothorax as the dominant reasons. Early readmission was primarily associated with pneumothorax and pneumonia, while late readmission correlated mainly with pneumonia.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Diagnosis and management of pneumonitis following chemoradiotherapy and immunotherapy in stage III non-small cell lung cancer.

BACKGROUND: In inoperable stage III NSCLC, the standard of care is chemoradiotherapy and adjuvant durvalumab (IO) for 12 months. Pneumonitis is the commonest toxicity leading to discontinuation of IO. A failure to distinguish between expected radiation-induced changes, IO pneumonitis and infection can lead to unnecessary durvalumab discontinuation. We investigated the use of a structured multidisciplinary review of CT-scans, radiation dose distributions and clinical symptoms for the diagnosis of IO pneumonitis. METHODS: A retrospective study was conducted at an academic medical center for patients treated for stage III NSCLC with chemoradiotherapy and adjuvant durvalumab between 2018 and 2021. An experienced thoracic radiologist reviewed baseline and follow-up chest CT-scans, systematically scored radiological features suspected for pneumonitis using a published classification system (Veiga C, Radioth Oncol 2018), and had access to screenshots of radiation dose distributions. Next, two experienced thoracic oncologists reviewed each patients' case record, CT-scans and radiation fields. A final consensus diagnosis incorporating views of expert clinicians and the radiologist was made. RESULTS: Among the 45 included patients, 14/45 (31.1%) had a pneumonitis scored in patient records and durvalumab was discontinued in 11/45 cases (24.4%). Review by the radiologist led to a diagnosis of immune-related pneumonitis only in 6/45 patients (13.3%). Review by pulmonary oncologists led to a diagnosis of immune-related pneumonitis in only 4/45 patients (8.9%). In addition a suspicion of an immune-related pneumonitis was rejected in 3 separate patients (6.7%), after the thoracic oncologists had reviewed the patients' radiation fields. CONCLUSIONS: In patients treated using the PACIFIC regimen, multidisciplinary assessment of CT-scans, radiation doses and patient symptoms, resulted in fewer diagnoses of immune-related pneumonitis (8.9%). Our study underscores the challenges in accurately diagnosing either IO-related or radiation pneumonitis in patients undergoing adjuvant immunotherapy after chemoradiotherapy and highlights the need for multidisciplinary review in order to avoid inappropriate cessation of adjuvant IO.

Dynamic immune signatures of patients with advanced non-small-cell lung cancer for infection prediction after immunotherapy.

Background: Pulmonary infections are a crucial health concern for patients with advanced non-small-cell lung cancer (NSCLC). Whether the clinical outcome of pulmonary infection is influenced by immunotherapy(IO) remains unclear. By evaluating immune signatures, this study investigated the post-immunotherapy risk of pulmonary infection in patients with lung cancer and identified circulating biomarkers that predict post-immunotherapy infection. Methods: Blood specimens were prospectively collected from patients with NSCLC before and after chemotherapy(C/T) and/or IO to explore dynamic changes in immune signatures. Real-world clinical data were extracted from medical records for outcome evaluation. Mass cytometry and ELISA were employed to analyze immune signatures and cytokine profiles to reveal potential correlations between immune profiles and the risk of infection. Results: The retrospective cohort included 283 patients with advanced NSCLC. IO was associated with a lower risk of pneumonia (odds ratio=0.46, p=0.012). Patients receiving IO and remained pneumonia-free exhibited the most favorable survival outcomes compared with those who received C/T or developed pneumonia (p<0.001). The prospective cohort enrolled 30 patients. The proportion of circulating NK cells significantly increased after treatment in IO alone (p<0.001) and C/T+IO group (p<0.01). An increase in cell densities of circulating PD-1+CD8+(cytotoxic) T cells (p<0.01) and PD-1+CD4+ T cells (p<0.01) were observed in C/T alone group after treatment. In IO alone group, a decrease in cell densities of TIM-3+ and PD-1+ cytotoxic T cells (p<0.05), and PD-1+CD4+ T cells (p<0.01) were observed after treatment. In C/T alone and C/T+IO groups, cell densities of circulating PD-1+ cytotoxic T cells significantly increased in patients with pneumonia after treatment(p<0.05). However, in IO alone group, cell density of PD-1+ cytotoxic T cells significantly decreased in patients without pneumonia after treatment (p<0.05). TNF-α significantly increased after treatment with IO alone (p<0.05) but decreased after C/T alone (p<0.01). Conclusions: Our results indicate that the incorporation of immunotherapy into treatment regimens may potentially offer protective effects against pulmonary infection. Protective effects are associated with reduction of exhausted T-cells and augmentation of TNF-α and NK cells. Exhausted T cells, NK cells, and TNF-α may play crucial roles in immune responses against infections. These observations highlight the potential utility of certain circulating biomarkers, particularly exhausted T cells, for predicting post-treatment infections.

Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial.

BACKGROUND: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma. METHODS: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1-2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, and on days 1 and 11 for cycles 3-4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1-28 for cycles 1-3; thereafter, up to 15 mg orally on days 1-28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1-6, and on day 1 for cycles 7-26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with ClinicalTrials.gov, NCT02495922, and is completed. FINDINGS: Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7-55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value, p=0·86), and 3-year progression-free survival rates were 69% (95% CI 61-77), 69% (61-76), 66% (58-74), and 67% (59-75) for patients treated with RVd/R, RVd/E-R, E-RVd/R, and E-RVd/E-R, respectively. Infections (grade 3 or worse) were the most frequently observed adverse event in all treatment groups (28 [20%] of 137 for RVd/R; 32 [23%] of 138 for RVd/E-R; 35 [25%] of 138 for E-RVd/R; and 48 [34%] of 142 for E-RVd/E-R). Serious adverse events (grade 3 or worse) were observed in 68 (48%) of 142 participants in the E-RVd/E-R group, 53 (39%) of 137 in the RVd/R, 53 (38%) of 138 in the RVd/E-R, and 50 (36%) of 138 in the E-RVd/R (36%) group. There were nine treatment-related deaths during the study. Two deaths (one sepsis and one toxic colitis) in the RVd/R group were considered lenalidomide-related. One death in the RVd/E-R group due to meningoencephalitis was considered lenalidomide and elotuzumab-related. Four deaths (one pulmonary embolism, one septic shock, one atypical pneumonia, and one cardiovascular failure) in the E-RVd/R group and two deaths (one sepsis and one pneumonia and pulmonary fibrosis) in the E-RVd/E-R group were considered related to lenalidomide or elotuzumab, or both. INTERPRETATION: Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma. FUNDING: Bristol Myers Squibb/Celgene and Chugai.

A dynamic nomogram predicting symptomatic pneumonia in patients with lung cancer receiving thoracic radiation.

PURPOSE: The most common and potentially fatal side effect of thoracic radiation therapy is radiation pneumonitis (RP). Due to the lack of effective treatments, predicting radiation pneumonitis is crucial. This study aimed to develop a dynamic nomogram to accurately predict symptomatic pneumonitis (RP ≥ 2) following thoracic radiotherapy for lung cancer patients. METHODS: Data from patients with pathologically diagnosed lung cancer at the Zhongshan People's Hospital Department of Radiotherapy for Thoracic Cancer between January 2017 and June 2022 were retrospectively analyzed. Risk factors for radiation pneumonitis were identified through multivariate logistic regression analysis and utilized to construct a dynamic nomogram. The predictive performance of the nomogram was validated using a bootstrapped concordance index and calibration plots. RESULTS: Age, smoking index, chemotherapy, and whole lung V5/MLD were identified as significant factors contributing to the accurate prediction of symptomatic pneumonitis. A dynamic nomogram for symptomatic pneumonitis was developed using these risk factors. The area under the curve was 0.89(95% confidence interval 0.83-0.95). The nomogram demonstrated a concordance index of 0.89(95% confidence interval 0.82-0.95) and was well calibrated. Furthermore, the threshold values for high- risk and low- risk were determined to be 154 using the receiver operating curve. CONCLUSIONS: The developed dynamic nomogram offers an accurate and convenient tool for clinical application in predicting the risk of symptomatic pneumonitis in patients with lung cancer undergoing thoracic radiation.

Fractures and other chest wall abnormalities after thoracotomy for esophageal cancer: A retrospective cohort study.

BACKGROUND: Chest pain following a thoracotomy for esophageal cancer is frequently reported but poorly understood. This study aimed to (1) determine the prevalence of thoracotomy-related thoracic fractures on postoperative imaging and (2) compare complications, long-term pain, and quality of life in patients with versus without these fractures. METHODS: This retrospective cohort study enrolled patients with esophageal cancer who underwent a thoracotomy between 2010 and 2020 with pre- and postoperative CTs (<1 and/or >6 months). Disease-free patients were invited for questionnaires on pain and quality of life. RESULTS: Of a total of 366 patients, thoracotomy-related rib fractures were seen in 144 (39%) and thoracic transverse process fractures in 4 (2%) patients. Patients with thoracic fractures more often developed complications (89% vs. 74%, p = 0.002), especially pneumonia (51% vs. 39%, p = 0.032). Questionnaires were completed by 77 after a median of 41 (P25 -P75 28-91) months. Long-term pain was frequently (63%) reported but was not associated with thoracic fractures (p = 0.637), and neither were quality of life scores. CONCLUSIONS: Thoracic fractures are prevalent in patients following a thoracotomy for esophageal cancer. These thoracic fractures were associated with an increased risk of postoperative complications, especially pneumonia, but an association with long-term pain or reduced quality of life was not confirmed.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Seasonal patterns of toxicity in melanoma patients treated with combination anti-PD-1 and anti-CTLA-4 immunotherapy.

BACKGROUND: Immune checkpoint inhibitors are frequently associated with the development of immunotherapy-related adverse events (irAEs). The exact etiology, including the role of environmental factors, remains incompletely understood. METHODS: We analyzed the records of 394 melanoma patients from three centers (northern and southern hemisphere). Patients had received at least one cycle of anti-PD-1/anti-CTLA-4 with a minimum follow-up of 3 months. We study the distribution and time to irAEs onset throughout the calendar year. RESULTS: 764 irAEs were recorded; the most frequent were skin rash (35%), hepatitis (32%) and colitis (30%). The irAEs incidence was the highest in autumn and winter, and the ratio for the 'number of irAEs' per 'therapies commenced' was the highest in winter and lowest in summer (2.4 and 1.7, respectively). Season-specific patterns in the time of irAEs onset were observed for pneumonitis (shorter time to onset in autumn, p = 0.025), hepatitis (shorter time to onset in spring, p = 0.016) and sarcoid-like immune reaction (shorter time to onset in autumn, p = 0.041). Season-specific patterns for early-onset irAEs were observed for hepatitis (spring, p = 0.023) and nephritis (summer, p = 0.017). Early-onset pneumonitis was more frequent in autumn-winter (p = 0.008) and early-onset nephritis in spring-summer (p = 0.004). CONCLUSIONS: Environmental factors that are associated with particular seasons may contribute to the development of certain irAEs and suggest the potential effect of environmental triggers. The identification of these factors may enhance preventive and therapeutic strategies to reduce the morbidity of irAEs.

Patients With Cystic Fibrosis Undergoing Total Hip and Total Knee Arthroplasty Are at Increased Risk for Perioperative Complications.

INTRODUCTION: Patients with cystic fibrosis (CF) are living longer and may be considered for total hip arthroplasty (THA) or total knee arthroplasty (TKA). Perioperative outcomes and implant survival after these procedures performed for those with CF have not been previously described. METHODS: Using the M151 PearlDiver database, a large, national, administrative database, THA and TKA patients with and without CF were identified and matched 1:10 based on age, sex, and Elixhauser Comorbidity Index. Ninety-day perioperative outcomes and 2-year revision rates were assessed and compared with multivariable logistic regression. RESULTS: For THA, 185 patients with CF were matched with 1,846 control subjects without CF. Patients with CF were at significantly increased odds of 90-day postoperative events including sepsis (odd radio [OR] 4.15), pneumonia (OR 3.40), pleural effusion (OR 2.77), minor events (OR 1.73), any adverse event (OR 1.64), urinary tract infection (UTI) (OR 1.63), and severe events (OR 1.60) ( P < 0.05 for each). For TKA, 505 patients with CF were matched with 5,047 control subjects without CF. Patients with CF were at significantly increased odds of 90-day postoperative events including pneumonia (OR 4.95), respiratory failure (OR 4.31), cardiac event (OR 2.29), minor events (OR 2.16), pleural effusion (OR 2.35), severe events (OR 2.06), urinary tract infection (OR 2.06), any adverse event (OR 1.96), atelectasis (OR 1.94), and acute kidney injury (OR 1.61) ( P < 0.05 for each). For both THA and TKA, those with CF were not at greater odds of 2-year rates of revision. DISCUSSION: After THA and TKA, those with CF were found to be at increased odds of multiple defined postoperative events (predominantly infectious/pulmonary), but not 2-year revision rates. These findings help define areas in need of focused optimization and are reassuring regarding risks of surgery.

Association of Cholinesterase With Postoperative Pneumonia After Gastrectomy for Gastric Cancer.

INTRODUCTION: Cholinesterase is a classical marker that reflects nutritional and inflammatory status. The aim of the present study was to evaluate the association between serum cholinesterase levels and postoperative infectious complications in patients undergoing gastrectomy for gastric cancer. MATERIALS AND METHODS: This retrospective study comprised 108 patients who underwent gastrectomy for gastric cancer. We comprehensively investigated the association between clinicopathological variables and postoperative infectious complications after gastrectomy. Then patients were divided into the cholinesterase-high and -low groups to analyze their clinicopathological variables. Finally, we analyzed the types of infectious complications that were most associated with preoperative serum cholinesterase levels. RESULTS: Twenty-six patients (24%) developed postoperative infectious complications. Multivariate analysis revealed that serum cholinesterase levels (P = 0.026) and N stage (P = 0.009) were independent risk factors for postoperative infectious complications. In particular, the incidence of pneumonia (P = 0.001) was significantly higher in the cholinesterase-low group. Age (P = 0.023), cerebrovascular comorbidities (P = 0.006), serum cholinesterase levels (P = 0.013), and total gastrectomy (P = 0.017) were identified as independent risk factors for postoperative pneumonia. CONCLUSIONS: Preoperative serum cholinesterase levels were associated with postoperative pneumonia after gastrectomy for gastric cancer, suggesting the importance of preoperative nutritional assessment in gastric cancer surgery.

MTOR Suppresses Cigarette Smoke-Induced Airway Inflammation and MMP12 Expression in Macrophage in Chronic Obstructive Pulmonary Disease.

Background: Macrophage-derived matrix metalloproteinase 12 (MMP12) can cause destruction of lung tissue structure and plays a significant role in the development and progression of chronic obstructive pulmonary disease (COPD). MTOR is a serine/threonine kinase that plays a crucial role in cell growth and metabolism. The activity of MTOR in the lung tissues of COPD patients also shows significant changes. However, it is unclear whether MTOR can regulate the development and progression of COPD by controlling MMP12. This study primarily investigates whether MTOR in macrophages can affect the expression of MMP12 and participate in the progression of COPD. Methods: We tested the changes in MTOR activity in macrophages exposed to cigarette smoke (CS) both in vivo and in vitro. Additionally, we observed the effect of MTOR on the expression of MMP12 in macrophages and on lung tissue inflammation and structural damage in mice, both in vivo and in vitro, using MTOR inhibitors or gene knockout mice. Finally, we combined inhibitor treatment with gene knockout to demonstrate that MTOR primarily mediates the expression of MMP12 through the NF-κB signaling pathway. Results: Exposure to CS can enhance MTOR activity in mouse alveolar macrophages. Inhibiting the activity of MTOR or suppressing its expression leads to increased expression of MMP12. Myeloid-specific knockout of MTOR expression can promote the occurrence of CS-induced pulmonary inflammation and emphysema in mice. Inhibiting the activity of NF-κB can eliminate the effect of MTOR on MMP12. Conclusion: Macrophage MTOR can reduce the expression of MMP12 by inhibiting NF-κB, thereby inhibiting the occurrence of COPD inflammation and destruction of lung tissue structure. Activating the activity of macrophage MTOR may be beneficial for the treatment of COPD.