Immune checkpoint inhibitors (ICIs) have heralded the advent of a new era in oncology by holding the promise of prolonged survival in severe and otherwise treatment-refractory advanced cancers. However, the remarkable antitumor efficacy of these agents is overshadowed by their potential for inducing autoimmune toxic effects, collectively termed immune-related adverse events (irAEs). These autoimmune adverse effects are often difficult to predict, possibly permanent, and occasionally fatal. Hence, the identification of risk factors for irAEs is urgently needed to allow for prompt therapeutic intervention. This review discusses the potential mechanisms through which irAEs arise and summarizes the existing evidence regarding risk factors associated with the occurrence of irAEs. In particular, we examined available data regarding the effect of a series of clinicopathological and demographic factors on the risk of irAEs.

An accurate estimation of prognosis of the esophageal carcinoma patients after surgery is urgently needed. Clinical nomogram has been developed to quantify risk by incorporating prognostic factors for individual patient. Based on the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013, a total of 4566 patients were selected. Of those, 3198 patients were assigned to training set to construct the nomogram, which incorporated age, gender, histology, grade, T stage, N stage, nodes examined, radiation and chemotherapy. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram was 0.71(95%CI 0.70-0.72), which was statistically higher than the TNM staging system. The results were then validated using bootstrap resampling and a validation set of 1368 patients in the SEER database. Besides, in the esophageal squamous cell carcinoma and esophageal adenocarcinoma subgroups, the nomogram discrimination was superior to the TNM staging system. It is likely that these results would play a supplementary role in the current staging system and help to identify the high risk population after surgery.

Background: There is a complex interplay between inflammatory response and coagulation in sepsis. Heparin is used as a recognized anticoagulant and possesses multiple biological properties that possibly affect sepsis. This study aimed to determine the possible signaling pathways involved in the anti-inflammatory effects of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs).Methods: HPMECs were transfected with siRNA targeting IκB-α. Cells were treated with UFH (0.01 U/ml~10 U/ml) 15 min before adding LPS (10 μg/ml). We detected the markers of systemic inflammatory response. Release of interleukin (IL)-6, IL-8 were evaluated at 3 h by ELISA and at 1 h by qRT-PCR. After 1 h, nuclear factor-κB (NF-κB) as well as phosphorylated inhibitor κB-α (IκB-α), signal transducer and activator of transcription-3 (STAT3) and ERK1/2, JNK, p38 mitogen-activated protein kinase (MAPK) expressions were evaluated by Western blot. DNA binding was conducted to further prove the activation of NF-κB pathway.Results: In HPMECs, UFH obviously inhibited LPS-stimulated production of IL-6 and IL-8, especially in 10 U/ml. UFH inhibited LPS-induced phosphorylation of IκB-α, ERK1/2, JNK, p38 MAPK and STAT3. UFH also suppressed LPSstimulated nuclear translocation of NF-κB. Importantly, transfection with siRNA targeting IκB-α induced more obvious inflammatory response. UFH suppressed cytokines production and phosphorylation of different signaling pathways in IκB-α silencing cells.Conclusion: These results demonstrate that UFH exerts the anti-inflammatory effects on LPS-stimulated HPMECs by different signaling pathways.

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Background Less is known about the risk factors for acute respiratory distress syndrome (ARDS) in sepsis patients diagnosed according to sepsis 3.0 criteria. Moreover, the risk factors for ARDS severity remain unclear. Methods We retrospectively collected the characteristics of sepsis patients from the intensive care unit of the First Affiliated Hospital of China Medical University from January 2017 to September 2018. Logistic regression was used in determining the risk factors. Results 529 patients with sepsis were enrolled and 179 developed ARDS. The most common infection sites were acute abdominal infection (n = 304) and pneumonia (n = 117). Multivariate analysis showed that patients with pancreatitis with local infection (odds ratio [OR], 3.601; 95% confidence interval [CI], 1.429–9.073, P = 0.007), pneumonia (OR 3.486; 95% CI 1.890–6.430, P < 0.001), septic shock (OR 2.163; 95% CI 1.429–3.275, P < 0.001), a higher sequential organ failure assessment (SOFA) score (OR 1.241; 95% CI 1.155–1.333, P < 0.001) and non-pulmonary SOFA score (OR 2.849; 95% CI 2.113–3.841, P < 0.001) were independent risk factors for ARDS. Moreover, pneumonia is associated with increased severity of ARDS (OR 2.512; 95% CI 1.039–6.067, P = 0.041). Conclusions We determined five risk factors for ARDS in sepsis patients. Moreover, pneumonia is significantly associated with an increased severity of ARDS.

Background: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune-related adverse events (irAEs) remain poorly understood, especially in a real-world setting.

Background Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non‐small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long‐term survival in NSCLC patients. Methods Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis. Results There was no significant distinction in overall survival (OS) between right ( n = 53 496) and left ( n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756–1.011; P = 0.432). Left side was associated with superior five‐year cancer‐specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574–0.9969; P = 0.024). No significant difference was observed in OS ( P = 0.689) or CSS ( P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side ( n = 21 245) was associated with poor OS compared to right side ( n = 30 074) NSCLC (HR 1.039, 95% CI 1.011–1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997–1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS ( P = 0.986) or CSS ( P = 0.979) after PSM analysis. Conclusion The prognosis between right and left side NSCLC in stage I–IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment.

Primary malignant melanoma of the lung is an extremely rare pulmonary carcinoma. Only 45 cases have been reported in the literature. Herein, we report a case of a 46‐year‐old male patient with an O Rh negative blood type who presented with pulmonary bronchial symptoms and underwent lobectomy. Genetic testing was also performed but no targetable mutations were found, and the patient's PD‐L1 RNA level was low. He developed brain metastasis four months after surgery and received radiotherapy but died 21 months after diagnosis. We review the published cases of this rare pulmonary lesion.