Background: Rapid molecular testing enhances pathogen detection in community-acquired pneumonia (CAP), yet its impact on clinical outcomes remains uncertain. We evaluated whether early precision treatment (PT) guided by evolving molecular diagnostics improves in-hospital mortality, and sought to identify specific patient subgroups that derive the greatest survival benefit. Methods: The multicentre retrospective CCAPP cohort study (June 2005–July 2024) included 2430 adults hospitalised with CAP across four general hospitals in Fujian Province, China, yielding 1904 patients with complete data for final analysis. Patients were categorized by diagnostic strategy: limited-target (LND; n=794; 11 bacterial and atypical pathogens) or diverse-target (DND; n=678; 33 bacterial, atypical, fungal, and viral pathogens) nucleic acid detection, or metagenomic next-generation sequencing (mNGS; n=432). On the basis of whether empirical anti-infective regimens administered within 3 days of admission covered clinically relevant pathogens, patients were classified as PT, non-precision treatment (NP), or no pathogen detected (NPD), and were further stratified into respiratory failure (RF) and non-respiratory failure (nRF) subgroups. Primary outcome was in-hospital mortality; secondary outcomes included length of stay and hospital costs. Confounding was addressed via 1:1:1 triad matching (PT:NP:NPD) in the DND (n=318) and mNGS (n=111) cohorts, analysed using conditional logistic regression and Kaplan-Meier methods. Findings: Pathogen positivity was 23·8% (LND), 60·0% (DND), and 32·6% (mNGS). PT was associated with significantly lower mortality compared with NP exclusively in the mNGS cohort, observed in both the overall population (3·4% vs 18·1%, p<0·001) and the RF subgroup (6·5% vs 34·1%, p=0·002). After matching, logistic regression in the DND cohort revealed that PT mortality benefit was strictly confined to the RF subgroup (OR 0·17, 95% CI 0·01–0·98; p=0·049; overall OR 0·43, p=0·220). Distinctly, PT in the mNGS cohort was associated with markedly lower mortality across both the overall population (OR 0·20, 95% CI 0·05–0·88; p=0·034) and the RF subgroup. Survival analyses corroborated this divergence: survival benefits for PT were consistent across the entire mNGS cohort (overall p=0·027; RF p=0·022), whereas DND-era benefits remained restricted to RF patients (p=0·040). PT did not significantly reduce length of stay or costs compared with non-PT. Interpretation: For hospitalised CAP, standard empirical therapy suffices for nRF patients, as PT yields no additional survival benefit, nor does it decrease length of stay or total costs. Conversely, RF patients derive substantial mortality reduction from PT guided by broad-spectrum diagnostics. While mNGS maximizes this protective effect, DND serves as a pragmatic alternative in resource-constrained settings.

Post-COVID-19 pulmonary fibrosis represents a significant long-term complication affecting 10–30

To compare the effectiveness of a generative artificial intelligence (GenAI)-assisted case-based learning model versus traditional teaching in a clinical diagnostics course. A quasi-experimental study was conducted with 84 fourth-year medical students cluster-assigned to an AI group (n = 42, using DeepSeek platform) or a control group (n = 42, using textbooks and clinical guidelines). Both groups received equal contact time (120 min/session) and feedback frequency (two iterative rounds). Assessments included theoretical knowledge tests at baseline, immediately post-course, and at 6-month follow-up, as well as critical thinking (CTDI-CV), self-directed learning (SRSSDL-CV), and teaching satisfaction. Linear mixed models with class as random intercept and baseline scores as fixed covariates were used, with Benjamini-Hochberg FDR correction for multiple comparisons (q-value < 0.05 considered statistically significant). No significant baseline differences were observed. Post-course theoretical scores showed comparable improvements across all knowledge domains (all q > 0.05). At 6 months, the AI group demonstrated significantly attenuated knowledge decay in symptomatology (adjusted difference = 2.1, 95

The regulatory mechanisms driving brain metastasis (BM) in non-small cell lung cancer (NSCLC) are complex, with Ceramide synthase 1 (Cers1) playing a critical role. However, the upstream factors controlling Cers1 expression remain unclear. Additionally, Kruppel-like factor 9 (KLF9) has been implicated as a potential tumor suppressor transcription factor (TF) in lung cancer. Our study aims to explore the physiological effects and molecular mechanisms of Cers1 upstream regulatory TFs in NSCLC BM, focusing on the link between KLF9 and Cers1. TFs regulating Cers1 expression were screened via GENECARD and UCSC databases. KLF9 expression and survival analysis in NSCLC were analyzed using TCGA and GEO data sets. Dual-luciferase assays were conducted to investigate the specific binding site of KLF9 on the Cers1 promoter. KLF9 genetic modulation impact on NSCLC BM was assessed through in vitro assays for proliferation, migration, and invasion, along with in vivo orthotopic xenograft models to evaluate tumor growth and metastasis. Our study revealed a significant downregulation of KLF9 in vitro, correlating with poor prognosis. KLF9 has a direct positive transcriptional regulation on Cers1, particularly on its promoter region (-711 nt/+22 nt). In vitro, KLF9 overexpression inhibited the ability of cells to penetrate a blood-brain barrier model. Moreover, in vivo experiments demonstrated a marked suppression of BM tumor formation upon KLF9 expression. This study reports KLF9's direct control over Cers1 expression by acting on its promoter. KLF9 demonstrates inhibitory effects on NSCLC BM, presenting a promising therapeutic avenue for NSCLC BM treatment.

Background:Bone is a common site of metastasis in non-small cell lung cancer (NSCLC), yet no validated prognostic model is currently available for patients presenting with bone metastases at diagnosis. Methods:We retrospectively reviewed 1,299 NSCLC patients who underwent high-throughput sequencing between 2016 and 2023. Of these, 195 were diagnosed with bone metastases at presentation. Three machine learning algorithms were applied to identify prognostic variables. A nomogram constructed with Cox regression was used to predict overall survival (OS) and was internally validated with 1,000 bootstrap resamples. Results:Four independent prognostic factors were identified, including age, serum calcium, monocyte-to-albumin ratio, and prognostic nutritional index. The nomogram demonstrated strong predictive performance, with areas under the curve (AUCs) of 86.53%, 78.32%, and 77.85% for 6-month, 1-year, and 2-year OS, respectively. Calibration plots showed excellent agreement between predicted and observed survival outcomes. Conclusion:This validated nomogram provides a practical and individualized tool for predicting survival in NSCLC patients with bone metastases at diagnosis, supporting risk stratification and clinical practice.

Locally advanced non-small cell lung cancer (NSCLC) has the potential for surgical cure after neoadjuvant immunotherapy in the era of immunotherapy. In this study, we conducted a meta-analysis of published data to systematically assess the efficacy and safety of neoadjuvant chemoimmunotherapy for stage III NSCLC. A comprehensive search was conducted on the Cochrane Library, PubMed, Web of Science, and Embase databases from January, 2000 to September, 2024 to identify studies concentrated on neoadjuvant chemoimmunotherapy followed by surgery for treating stage III NSCLC. The effectiveness and safety data were collected for meta-analysis. Study endpoints included resection rate, major pathological response (MPR), pathological complete response (pCR), objective response rate (ORR), treatment-related adverse events (TRAEs), severe adverse events (SAEs). Data analysis was conducted using R 4.1.3 software, and P < 0.05 was considered statistically significant. A total of 1043 patients from 22 studies were included in this meta-analysis, of whom 892 cases underwent surgery. The pooled MPR rate, pCR rate, and ORR rate were 65

Tumor mutational burden (TMB) is a recognized biomarker for predicting immunotherapy efficacy in non-small cell lung cancer (NSCLC). Its assessment requires whole-exome sequencing (WES), but the high cost and stringent sample requirements of WES limit its clinical application. This study aims to assess the predictive value of accessible systemic inflammation markers for identifying high TMB lung cancer populations. WES was performed on tumor samples and paired peripheral blood from 72 lung adenocarcinoma patients. Genomic analysis identified mutation patterns across different TMB groups. Systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR), were collected. Generalized linear models and restricted cubic spline (RCS) plots were used to explore the predictive value of these markers for TMB. The Xgboost model assessed the importance of each variable for TMB prediction. Among the 72 lung adenocarcinoma patients, missense mutations were the most common, with single nucleotide variants being the predominant mutation type. The most frequently mutated genes were EGFR (35

ObjectiveThis study aims to investigate the clinical application value of Metagenome Next-Generation Sequencing (mNGS) for pulmonary diffuse exudative lesions.MethodsFrom January 1, 2014, to November 31, 2021, 136 cases with chest radiologic presentations of pulmonary diffuse exudative lesions admitted to Fujian Provincial Hospital were included in the study; of those, 77 patients underwent mNGS pathogen detection. Based on the pathogen detection outcomes and clinical diagnoses, patients were categorized into an infection group (IG) and a non-infection group (NIG). A comparison was made between the diagnostic efficacy of the mNGS technique and traditional culture methods. Meanwhile, 59 patients clinically identified as having infectious pulmonary diffuse exudative lesions but who did not receive mNGS testing were designated as the non-NGS infection group (non-IG). A retrospective cohort study was conducted on patients in both the IG and non-IG, with a 30-day all-cause mortality endpoint used for follow-up.OutcomesWhen compared to conventional culture methods, mNGS demonstrated an approximate 35% increase in sensitivity (80.0% vs 45.5%, P<0.001), without significant disparity in specificity (77.3% vs 95.5%, P=0.185). Under antibiotic exposure, the positivity rate detected by mNGS was notably higher than that by traditional culture methods, indicating that mNGS is less affected by exposure to antibiotics (P<0.05). Within 30 days, the all-cause mortality rate for patients in the IG versus the non-IG was 14.55% and 37.29%, respectively (P<0.05). Following a COX regression analysis to adjust for confounding factors, the analysis revealed that a CURB-65 score ≥3 points (HR=3.348, P=0.001) and existing cardiovascular disease (HR=2.473, P=0.026) were independent risk factors for these patients. Conversely, mNGS testing (HR=0.368, P=0.017) proved to be an independent protective factor.ConclusionmNGS technology makes it easier to pinpoint the cause of pulmonary diffuse infectious exudative lesions without much interference from antibiotics, helping doctors spot and diagnose these issues early on, thereby playing a key role in helping them decide the best treatment approach for patients. Such conclusions may have a bias, as the performance of traditional methods might be underestimated due to the absence of complete results from other conventional diagnostic techniques like serological testing and PCR.

Third-generation EGFR-TKIs can be used to treat advanced non-small cell lung cancer patients with T790M resistance mutation induced by first- or second-generation EGFR-TKIs. However, it will also result in drug resistance, and the resistance mechanisms of third-generation EGFR-TKIs are complex. Here we reported a patient diagnosed with advanced lung adenocarcinoma and EGFR positive in September 2016. Following first-line targeted therapy with gefitinib, genetic testing showed EGFR T790M positive, which resulted in a change to osimertinib targeted therapy. In May 2021, troponin and creatinine levels were elevated, and the tumor hyperprogressed to severe lung cancer. Repeated genetic testing revealed that EGFR genotype converted to a non-classical mutation and EGFR T790M turned negative, which caused third-generation EGFR-TKI resistance. As a result, afatinib combined with anlotinib was selected to stabilize the patient’s condition. We were inspired by the case that it reflects the significance and necessity of exploring the resistance mechanism and dynamically detecting genetic status throughout the course of treatment, which may help realize individualized precision therapy, and maximize the potential of patient.

Abstract Background Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM. Methods RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood–brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein–protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results. Results RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 ~ -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway. Conclusion RPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.

200 Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.

Abstract Objective To evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients. Methods 115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX. Results 68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043–1.725]) and 1.401(95%CI [1.013–1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633–0.893]) and 0.734(95%CI [0.570–0.899]) (DeLong’s test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making. Conclusion Evaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management. Trial registration Chinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14.

OBJECTIVE To investigate the clinical characteristics of non-tuberculous Mycobacteria pulmonary disease（NTMPD）, identify the species of non-tuberculous Mycobacteria（NTM） with metagenomic sequencing and perform the cluster analysis. METHODS A total of 79 patients who were diagnosed with NTMPD in Fujian Provincial Hospital from Jan 2015 to Dec 2020 were enrolled in the study, the related clinical data were collected, the whole genome sequencing was carried out for 29 clinical NTM isolates by means of metagenomic next generation sequencing（mNGS）, the average nucleotide identity（ANI） analysis was performed for identification of the strains, and the cluster heat map of the ANI value was drawn for the clinical NTM isolates. RESULTS The number of confirmed cases of NTMPD was increased year by year. Among the 79 patients with NTMPD, there were 40 male cases and 39 female cases, the average age was（60.78±12.04） years old, and about 55.70%（44/79） had bronchiectasia. Cough（86.08%） and expectoration（75.95%） were the major clinical manifestations of the NTMPD patients; bronchiectasis（55.70%, 44/79）, tree-in-bud signs（43.04%, 34/79） and nodules（35.44%, 28/79） were the common CT imaging features. Alveolar lavage fluid specimens were dominant among the specimens cultured positive for NTM, accounting for 60.76%（48/79）. Totally 10 species of NTM were identified among the 29 strains of NTM, 58.62% of which were Mycobacterium avium complex, and 24.14% were Mycobacterium abscess. Among the M.avium complex strains, M. intracellulare, M.paraintracellulare and M. chimera had close ties of consanguinity, and the fast-growing M. abscess was distantly related to slow-growing NTM strains. CONCLUSION The patients with NTMPD lack typical clinical symptoms. It is necessary to remain vigilant for the possibility of NTM infection among the patients with CT imaging manifested as bronchiectasis complicated with nodules and tree-in-bud signs. There is certain association between the genotypes and the phenotypes of the NTM strains.

目的 探讨慢阻肺急性加重期(AECOPD)患者合并不同代谢综合征组分数量的临床特征及出现Ⅱ型呼吸衰竭的危险因素.方法 回顾性分析2014年1月至2017年12月福建省立医院吸科收治的249例AECOPD患者的病历资料.根据代谢综合征(MS)合并数量将患者分为4组.对比4组间患者的临床差异特征.借助logistic回归分析对发生Ⅱ型呼吸衰竭(RF)的危险因素展开探究.结果 不同组间的住院时间、住院费用、慢性心力衰竭、冠状动脉粥样硬化、进入呼吸科重症监护室率组间差异有统计学意义(P<0.05);高密度脂蛋白胆

IntroductionThis study explored the differences in clinical characteristics between the 2009 pandemic influenza A (H1N1) and SARS-CoV-2 BA.2 variant (Omicron) infections in patients younger than age 65 years, to improve identification of these diseases and better respond to the current epidemic. MethodsData from 127 patients with the 2009 pandemic influenza A (H1N1) diagnosed between May and July of 2009 and 3,265 patients with Omicron diagnosed between March and May of 2022 were collected. Using a 1:2 match based on age (difference <2 years), sex, and underlying diseases, data from 115 patients with the 2009 pandemic influenza A (H1N1) infection (H1N1 group) and 230 patients with SARS-CoV-2 Omicron BA.2 infection (Omicron group) were analyzed. The clinical manifestations were compared between the groups, logistic regression was performed to identify possible independent risk factors for each group, and multiple linear regression was used to analyze the factors predicting time for nucleic acid negativization (NAN). ResultsThe median [interquartile range] age of the two groups was 21 [11, 26] years. Compared with the H1N1 group, the Omicron group had: lower white blood cell counts and C-reactive protein levels; less fever, nasal congestion, sore throat, cough, sputum, and headache; and more olfactory loss, muscle soreness, and lactate dehydrogenase (LDH) abnormalities. Patients in the Omicron group used fewer antibiotics and antiviral drugs, and the time for NAN was longer (17 [14,20] VS 4 [3,5] days, P<0.001). Logistic regression showed that fever, cough, headache, and increased white blood cell count were more strongly correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more strongly correlated with the Omicron group. Fever (B 1.529, 95% confidence interval [0.149,2.909], P=0.030) significantly predicted a longer time for NAN in patients with Omicron. DiscussionThere are significant differences in clinical characteristics between SARS-CoV-2 Omicron infection and the 2009 pandemic influenza A (H1N1) infection. Recognition of these differences has important implications for clinical practice.

BACKGROUND:This study aimed to compare the clinical characteristics of infections caused by different pathogens and then establish a viral/bacterial infection prediction model to guide early clinical identification of pathogens in inpatients with community-acquired pneumonia(CAP). METHODS:A total of 687 patients who were diagnosed with CAP in our hospital between March 2012 and December 2018 were studied.Basic data,clinical symptoms,laboratory examinations,and imaging examinations of patients were collected,and a virus/bacteria prediction equation was established.In the prediction model,the relevant variables were screened according to a univariate logistic regression analysis,and then,a multivariate logistic regression analysis was performed to establish the prediction equation. RESULTS:The proportions of patients with muscle soreness and headaches were significantly higher in the viral infection group than in the bacterial infection group.Procalcitonin(PCT)concentrations,the erythrocyte sedimentation rate(ESR),and the neutrophil alkaline phosphatase(NAP)score were significantly higher in the bacterial infection group than in the viral infection group.Creatine kinase concentrations were significantly higher in the viral infection group than in the bacterial infection group(P＜0.05).A higher proportion of patients had lung degeneration in the atypical pathogen infection group than in other groups(P=0.005).Patchy shadows were more common in the viral infection group than in the other groups.A binary logistic regression equation was obtained that could predict the probability of viral infection(sensitivity:57.5％,specificity:67.7％,and area under the receiver operating characteristics curve:0.651). CONCLUSIONS:Adult patients with CAP and viral infection are more likely to have headaches and muscle soreness than those with bacterial infection.An elevated PCT concentration,NAP score,and ESR indicate a high possibility of bacterial infection.We successfully established a viral and bacterial infection prediction model.

目的 探讨免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)伴骨转移的疗效,及ICIs免疫治疗的影响因素,为改善晚期NSCLC骨转移患者预后、指导个体化治疗提供临床依据.方法 回顾性分析2019年1月1日—2022年3月31日期间在福建省立医院收治的NSCLC合并骨转移患者的临床资料[性别、发病年龄、吸烟史、骨转移灶情况、病理类型、治疗方案、疗效、无进展生存期(progression free survival,PFS)、总生存期(overall survival,OS)等],随访取得患者的生存资料,运用生存分析(Kaplan-Meier生存时间曲线)评价ICIs的疗效,以单因素分析(Log-Rank)、多因素分析(Cox回归模型)预测影响ICIs疗效的因素.结果 纳入168例NSCLC骨转移患者,有84例接受ICIs治疗,1年生存率为71.43%(60/84),客观缓解率23.81%,疾病控制率84.52%.ICIs治疗组的中位无进展生存期(mid progression free survival,MPFS)为11.0个月(P = 0.018),中位生存期(median survival time,MST)为18.3个月(P = 0.045),差异有统计学意义.单因素分析显示,发病年龄＜65岁(P = 0.040)、初诊时美国东部肿瘤协作组体能状态评分标准(Eastern Cooperative Oncology Group Performance Status,ECOG-PS)评分≤1分(P = 0.006)、无其他器官转移(P = 0.001)、全身化疗(P = 0.006)、免疫联合治疗(P = 0.012)有更长的PFS;初诊时ECOG-PS≤1分(P = 0.043)、无其他器官转移(P = 0.001)、全身化疗(P = 0.034)有更长的OS;多因素分析显示,发病年龄≥65岁患者的PFS、OS(P = 0.012;P = 0.002)低于发病年龄＜65岁的患者;骨改良药物治疗患者的 PFS、OS 均明显高于无骨改良药物治疗的患者(P = 0.050;P = 0.035);伴其他器官转移患者的 PFS、OS 均明显低于无其他器官转移的患者(P = 0.001;P = 0.001);初诊时ECOG PS评分≥2分患者的PFS(P = 0.047)明显短于初诊时ECOG-PS评分≤1分患者的PFS.结论 ICIs明显延长NSCLC骨转移患者的PFS、OS;年龄越小(＜65岁)、体能状态良好(ECOG-PS评分≤1分)、无其他器官转移、免疫联合化疗的患者使用ICIs治疗效果更好;年龄越大(≥65岁)、体能状态偏差(ECOG-PS评分≥2分)、伴其他器官转移是肺癌骨转移患者使用ICIs免疫治疗病程进展的独立危险因素,并且发病年龄、伴其他器官转移是ICIs免疫治疗OS的独立预测因子,而骨改良药物骨治疗是NSCLC骨转移患者使用ICIs免疫治疗PFS、OS的独立保护因素.

Background Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear. Methods Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed. Results A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant ( OR 14.146, P = 0.004) and the lymphocyte counts < 0.7 × 10 9 /L ( OR 6.882 , P = 0.011) were risk factors for the development of PJP in non-HIV immunocompromised patients. 81.82% (27/33) and 64.71% (22/34) mixed infections were identified by mNGS in the PJP group and non-PJP group separately. CMV , EBV and Candida were the leading co-pathogens in PJP patients. The percentages of CMV and EBV identified by mNGS in PJP group were significantly higher than those in the control group( p < 0.005). Conclusions Clinicians should pay close attention to the development of PJP in non-HIV immunocompromised patients who possess the risk factors of concomitant use of corticosteroids and immunosuppressant and the lymphocyte counts < 0.7 × 10 9 /L. Prophylaxis for PJP cannot rely solely on CD4 + T counts in non-HIV immunocompromised patients. Whether CMV infection increases the risk of PJP remains to be further investigated.

Objective This study attempted to explore the difference of clinical characteristics in H1N1 influenza infection and SARS-CoV-2 Omicron infection in people younger than 65 years old, in order to better identify the two diseases. Methods A total of 127 H1N1 influenza patients diagnosed from May 2009 to July 2009 and 3265 patients diagnosed and identified as SARS-CoV-2 Omicron BA.2 variant from March 2022 to May 2022 were admitted in this study. Through the 1 : 2 match based on age (The difference is less than 2 years), gender and underlying diseases, 115 patients with H1N1 infection and 230 patients with SARS-CoV-2 Omicron BA.2 infection(referred to as H1N1 group and Omicron group) were included in the statistics. The clinical manifestations of H1N1 group were compared with those of Omicron group. Logistic regression was performed to analyze the possible independent risk factors of H1N1 group and Omicron group. And multiple linear regression was used to analyze the factors for time for nucleic acid negativization (NAN). Results The median age of the two groups was 21 [11,26] years. Compared with the H1N1 group, the Omicron group had lower white blood cell count and CRP levels, less fever, nasal congestion, sore throat, cough, sputum and headache, while more olfactory loss, muscle soreness and LDH abnormalities. The Omicron group used less antibiotics and antiviral drugs, and the NAN time was longer (17 [14,20] VS 4 [3,5], P < 0.001). After logistic regression, it was found that fever, cough, headache, and increased white blood cell count were more correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more correlated with the Omicron group. After analyzing the factors of NAN time, it was found that fever (B 1.529, 95 % CI [0.149,2.909], P = 0.030) significantly predicted longer NAN time in Omicron patients. Conclusion This study comprehensively evaluated the similarities and differences in clinical characteristics between SARS-CoV-2 Omicron infection and 2009 H1N1 influenza infection, which is of great significance for a better understanding for these diseases.