Prognostic Value of Neutrophil/Lymphocyte Ratio for Pulmonary Embolism: A Meta-Analysis and External Validation.

BACKGROUND: Prognostic value of neutrophil/lymphocyte ratio (NLR) for pulmonary embolism (PE) has been reported in several retrospective studies. The purpose of this investigation was to perform a pooled analysis and external validation of predictive value of NLR. METHODS: PubMed, Embase, and Cochrane databases were searched from inception to November 5, 2022. A random effects model was used. Grade was used to evaluate the certainty of evidence. External validation was conducted in clinical cohorts before and after a propensity scoring matching (PSM). Covariates include basic clinical characteristics, such as age, gender, etc. The value of NLR in prediction model was also evaluated. RESULTS: A total of 15 studies comprising 5,874 patients were included. Pooled risk ratio of NLR was 2.33 (95% confidence interval [CI]: 1.97-2.75), with an area under the curve of 0.78 (95% CI: 0.74-0.81), a sensitivity of 0.75 (95% CI: 0.71-0.79), a specificity of 0.67 (95% CI: 0.61-0.73), and a median cut-off value of 5.7. Grade of Recommendations Assessment Development and Evaluation (GRADE) certainty analysis showed the quality of the evidence was moderate. Before (n = 336) and after (n = 152) propensity scoring matching, risk ratio of NLR was 2.69 (95% CI: 1.04-6.97) and 6.58 (95% CI: 1.99-17.75). A prediction model consisting of NLR, age, D-dimer, and simplified PE severity index had an area under the curve of 0.809 (95% CI: 0.738-0.88), a sensitivity of 0.638 (95% CI: 0.511-0.745), and a specificity of 0.851 (95% CI: 0.709-0.917). Net reclassification index (12%, P = 0.035) and integrated discrimination improvement (17%, P = 0.022) indicated an improvement caused by NLR. CONCLUSIONS: Prognostic value of NLR for PE was confirmed by meta-analysis and validated in an independent cohort, deserving further clinical application.

Endovascular Stent Graft Repair for Mycotic Aorto-Iliac Aneurysm Due to Brucella.

PURPOSE: Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The current study aimed to assess the safety and efficacy of endovascular treatment for Brucella aneurysms. MATERIALS AND METHODS: The clinical data of 15 Brucella aortic-iliac aneurysm patients who underwent endovascular repair at 2 hospitals from January 2012 to December 2021 were retrospectively collected and analyzed. RESULTS: Fifteen patients (12 men and 3 women) with a mean age of 59.3 years were included. Fourteen patients (93.3%) had a history of exposure to animals (cattle and sheep). All patients had aortic or iliac pseudoaneurysms, 9 abdominal aortic aneurysms (AAAs), 4 iliac aneurysms, and 2 AAA combined with iliac aneurysms. Endovascular aneurysm repair (EVAR) was performed in all patients without conversion to open surgery. Six cases were treated for emergency surgery due to aneurysm rupture. The immediate technique success rate was 100%, with no postoperative death. Two cases had the iliac artery ruptured again after operation because of lack of antibiotic treatment and was given endovascular treatment again. Once brucellosis is diagnosed, antibiotic treatment with doxycycline and rifampicin was initiated for all the patients until 6 months after operation. All patients survived over a median follow-up period of 45 months. Follow-up computed tomography angiography showed that all stent grafts remained patent, with no endoleak. CONCLUSION: EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for these Brucella aneurysms. CLINICAL IMPACT: Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The traditional operation management strategy is surgical resection and debridement of the infected aneurysm and the surrounding tissues. However, open surgical management in these patients causes severe trauma with high surgical risks and mortality (13.3%-40%). We tried to treat Brucella aneurysms with endovascular therapy, and the technique success and survival rate of the operation reached 100%. EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for some mycotic aneurysms.

TRIB3 reduces CD8+ T cell infiltration and induces immune evasion by repressing the STAT1-CXCL10 axis in colorectal cancer.

High CD8+ T cell infiltration in colorectal cancer (CRC) should suggest a favorable prognosis and a satisfactory response to immunotherapy; however, the vast majority of patients with CRC do not benefit from immunotherapy due to poor T cell infiltration. Therefore, a better understanding of the mechanisms for T cell exclusion from CRC tumors is needed. Tribbles homolog 3 (TRIB3) has been implicated as an oncoprotein, but its role in regulating antitumor immune responses has not been defined. Here, we demonstrated that TRIB3 inhibits CD8+ T cell infiltration in various CRC mouse models. We showed that TRIB3 was acetylated by acetyltransferase P300, which inhibited ubiquitination and subsequent proteasomal degradation of TRIB3. Ectopically expressed TRIB3 inhibited signal transducer and activator of transcription 1 (STAT1) activation and STAT1-mediated CXCL10 transcription by enhancing the epidermal growth factor receptor signaling pathway, causing a reduction in tumor-infiltrating T cells. Genetic ablation of Trib3 or pharmacological acceleration of TRIB3 degradation with a P300 inhibitor increased T cell recruitment and sensitized CRCs to immune checkpoint blockade therapy. These findings identified TRIB3 as a negative modulator of CD8+ T cell infiltration in CRCs, highlighting a potential therapeutic target for treating immunologically "cold" CRCs.

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis.

BACKGROUND: Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy (NCRT). This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis. METHODS: In total, 1296 patients with NCRT or post-operative chemoradiotherapy (PCRT) were enrolled in this study between January 2008 and December 2015. Propensity score matching was used to correct for differences in baseline characteristics between the two groups. After propensity score matching, the metastasis pattern, including metastasis sites and timing, was compared and analyzed. RESULTS: After propensity score matching, there were 408 patients in the PCRT group and 245 patients in the NCRT group. NCRT significantly reduced local recurrence (4.1% vs. 10.3%, P = 0.004), but not distant metastases (28.2% vs. 27.9%, P = 0.924) compared with PCRT. In both the NCRT and PCRT groups, the most common metastasis site was the lung, followed by the liver. The NCRT group developed local recurrence and distant metastases later than the PCRT group (median time: 29.2 [18.8, 52.0] months vs. 18.7 [13.3, 30.0] months, Z = -2.342, P = 0.019; and 21.2 [12.2, 33.8] vs. 16.4 [9.3, 27.9] months, Z = -1.765, P = 0.035, respectively). The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group (39/114, 34.2%) and NCRT group (21/69, 30.4%). However, 20.3% (14/69) of the distant metastases appeared in the 3rd year in the NCRT group, while this number was only 13.2% (15/114) in the PCRT group. CONCLUSIONS: The predominant site of distant metastases was the lung, followed by the liver, for both the NCRT group and PCRT group. NCRT did not influence the predominant site of distant metastases, but the NCRT group developed local recurrence and distant metastases later than the PCRT group. The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.

Mapping the spreading routes of lymphatic metastases in human colorectal cancer.

Lymphatic metastases are closely associated with tumor relapse and reduced survival in colorectal cancer (CRC). How tumor cells disseminate within the lymphatic network remains largely unknown. Here, we analyze the subclonal structure of 94 tumor samples, covering the primary tumors, lymph node metastases (LNMs), and liver metastases from 10 CRC patients. We portray a high-resolution lymphatic metastatic map for CRC by dividing LNMs into paracolic, intermediate, and central subgroups. Among the 61 metastatic routes identified, 38 (62.3%) are initiated from the primary tumors, 22 (36.1%) from LNMs, and 1 from liver metastasis (1.6%). In 5 patients, we find 6 LNMs that reseed 2 or more LNMs. We summarize 3 diverse modes of metastasis in CRC and show that skip spreading of tumor cells within the lymphatic network is common. Our study sheds light on the complicated metastatic pattern in CRC and has great clinical implications.

Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention.

BACKGROUND: Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear. MATERIALS AND METHODS: We conducted a case-control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size-related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis. RESULTS: Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER-)/PR negative(PR-) subtype risks, although only significantly for ER+/PR+ subtype. Waist-hip ratio was only positively correlated with ER-/PR- subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER-/PR- subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR- and positively with ER-/PR- subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER-/PR- subtype. CONCLUSION: Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER-/PR- subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals. IMPLICATIONS FOR PRACTICE: The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight-control measures may be advised in these individuals.