BACKGROUND:Stereotactic body radiotherapy (SABR) plays an essential role in the curative treatment of early-stage lung cancer. Second primary malignancy (SPM) has become a significant concern in lung cancer management because of the increasing number of cancer survivors. However, whether SABR increases the risk of SPMs in early-stage lung cancer remains unknown. METHODS:Patients with T1-2N0M0 primary lung cancer who underwent either surgery or SABR between 2010 and 2015 were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. A Kaplan-Meier analysis was conducted to compare the cumulative incidence of SPMs between patients who underwent radiotherapy and those who underwent surgery. Multivariable Cox regression analyses were performed to evaluate the risk of SPMs. RESULTS:The study included 22,809 2-year early-stage lung cancer survivors (radiotherapy, 3236; surgery, 19,573) and 17,048 5-year survivors (radiotherapy, 1501; surgery, 15,547). 196 second haematologic cancers and 1642 second solid malignancies were diagnosed. SABR was not associated with a higher overall risk of second haematologic cancers or second solid malignancies. However, after adjusting for independent influencing factors of SPMs, SABR was associated with a 38.5% higher cumulative incidence of secondary primary lung cancer. The risk was increased only when compared to the lobectomy group. CONCLUSIONS:SABR for early-stage lung cancer was not associated with a higher overall risk of developing SPMs; however, it did increase the risk of second primary lung cancers when compared to the lobectomy group. Randomised controlled trials should be conducted in the future to validate our conclusions further.

Pneumocystis pneumonia constitutes a critical life-threatening opportunistic infection, where the host's immune response plays a central role in its pathogenesis. Immunocompetent individuals are typically capable of eradicating Pneumocystis without exhibiting clinical symptoms. In contrast, individuals with compromised immune systems are vulnerable to developing Pneumocystis pneumonia, which can lead to severe inflammatory responses and consequent pulmonary damage. This review examines the roles of innate immunity, particularly macrophages and adaptive immunity, including CD4+ and CD8+ T-cells, as well as key cytokines, in the defence against Pneumocystis infection across various host categories, namely immunocompetent individuals, those infected with HIV and non-HIV-infected individuals, especially those undergoing corticosteroid therapy. By integrating findings from animal models and clinical studies, this review seeks to enhance our understanding of the pathogenesis of Pneumocystis infection across varied immunological contexts.

IntroductionCarbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical global public health challenge due to its significant association with morbidity and mortality. Ceftazidime-avibactam (CZA) has emerged as an effective therapy against CRKP producing the serine carbapenemase KPC; however, resistance driven by novel KPC variants is increasingly reported.MethodsIn this study, 27 CRKP isolates were collected from elderly pneumonia patients in China. Sequential isolates from a single patient undergoing prolonged hospitalization revealed dynamic resistance evolution.ResultsWhole-genome sequencing identified KPC-227, a novel KPC variant, alongside the previously reported KPC-204. KPC-204, carrying a “DDK” insertion at position 270, conferred resistance to both carbapenems and CZA, while KPC-227, harboring a D179Y mutation, restored carbapenem susceptibility but maintained CZA resistance. Molecular docking analyses revealed that the D179Y mutation impaired meropenem hydrolysis by decreasing binding affinity. Additionally, colistin resistance was observed due to a novel mgrB mutation.DiscussionThese findings highlight the high evolutionary potential of KPC enzymes and the importance of vigilance to curb the emergence and dissemination of resistance, which threatens the efficacy of critical lastresort antibiotics.

Lung cancer remains the leading cause of death worldwide, yet optimal treatment strategies for octogenarians with early-stage non-small cell lung cancer (NSCLC) remain unclear. To investigate treatment patterns and survival outcomes in octogenarians and older with early-stage NSCLC. A retrospective cohort study was conducted using Surveillance, Epidemiology, and End Results database. Patients aged ≥ 80 years with stage I–IIA NSCLC diagnosed between 2011 and 2020 were included. Primary treatments included surgery, radiation, and no treatment. Kaplan–Meier curves were used to evaluate overall survival (OS) and cancer-specific survival (CSS) stratified by treatment and year. Propensity score matching balanced clinical characteristics between surgery and radiation groups, followed by Cox regression analysis. Survival outcomes were further compared within matched subgroups stratified by tumor size. Among 7,372 patients, median survival was 67 months for surgery and 33 months for radiotherapy. Radiotherapy use increased from 31.2

Background Glucocorticoids have been shown to be very effective in the treatment of Human Immunodeficiency Virus (HIV) associated Pneumocystis jirovecii Pneumonia (PCP). However, risk factors and the impact on prognosis in non-HIV-PCP patients remain unclear. Our study aimed to early identification risk factors and prognostic impact of glucocorticoids therapy in non-HIV-PCP patients to decrease patients’ mortality. Methods A retrospective study was conducted on adult (≥ 18 years old) patients diagnosed with non-HIV-PCP in Peking University First Hospital from April 2007 to October 2022. A total of 269 patients with non-HIV-PCP were hospitalized during the period, and 200 patients were eventually included. Demographic data and related clinical data were collected. Univariate and multivariate logistic regression were used to analyze the relationship between variables and poor prognosis. Results A total of 200 non-HIV-PCP patients were included. 29% (58/200) patients died during admission. Univariate analysis showed that age, history of chemotherapy, history of glucocorticoid, autoimmune disease, organ transplantation, respiratory failure, platelet count, neutrophil/lymphocyte ratio, highly sensitive C-reactive protein, albumin, lactic dehydrogenase, d-dimer, bronchoalveolar lavage fluid (BALF)-neutrophil percentage, BALF-lymphocyte percentage, hospital-acquired pneumonia associated pathogen infection, pneumothorax, mediastinal emphysema, caspofungin therapy and high dose (≥ 1mg/(kg· d)) glucocorticoids therapy have a risk of death due to PCP patients. Multivariate analysis showed that age (OR = 1.062, 95%CI 1.021–1.104, P = 0.003), hospital-acquired pneumonia associated pathogen infection (OR = 4.170, 95%CI 1.407–12.357, P = 0.010) and high dose glucocorticoid therapy (OR = 7.047, 95%CI 2.482–20.006, P < 0.001) were independent risk factors for in-hospital death in non-HIV-PCP patients. Conclusions Considering the rapid course of the disease in non-HIV-infected immunocompromised patients. Early identification of high-risk PCP patients is critical to reduce morbidity and mortality. Our study found that non-HIV-PCP patients treated with high doses of glucocorticoids, old age, history of chemotherapy and hospital-acquired pneumonia associated pathogen infection had worse outcomes during hospitalization.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient's oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.

Objective: This study investigated treatment patterns and survival outcomes in octogenarians with early-stage non-small cell lung cancer (NSCLC) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Data from the SEER 17 Registries (2000-2020) was analyzed. Patients aged 80 years or older who were diagnosed with early-stage NSCLC (stage I-IIA) between2011 and 2020 were included. Propensity score matching (PSM) was applied to balance clinical characteristics between treatment groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan‒Meier analysis and Cox regression. Results: A total of 31371 patients aged 80 years or older were diagnosed with NSCLC in the SEER database from 2011 to 2020, including 8042 patients with early-stage I–IIA (AJCC 8th) NSCLC, 7372 of whom met the study entry criteria. Early-stage NSCLC patients increased significantly to over 30% during 2018-2020, compared to less than 25% in 2011-2017. Over the decade, radiotherapy increased from 31.2% to 49.4%, while surgery decreased from 44.5% to 32.4%. Radiotherapy has surpassed surgery and been the predominant treatment for octogenarians since 2014. A total of 5496 patients were included in survival analysis. The mediansurvival was 67 months for patients who underwent surgery and 33 months for those who received radiotherapy. Lobectomy was associated withbetter long-term OS thansegmentectomy and wedge resection. Stratification by tumor size confirmed the superiority of surgery in most categories except for the smallest tumors (0-1 cm). Conclusions: The proportion of early-stage NSCLC patients aged 80 and older increased significantly in 2018-2020 compared to 2011-2017. Radiotherapy is increasingly used to treat early-stage NSCLC in octogenarians, yet surgery provides superior long-term survival. These findings support surgical intervention as the preferred treatment for eligible octogenarians with early-stage NSCLC.

BackgroundCompared with Human Immunodeficiency Virus (HIV) patients, non-HIV patients with Pneumocystis pneumonia (PCP) have more rapid onset, more rapid progression, and higher mortality.ObjectivesTo investigate the predictive value of variables obtained upon hospital admission for in-hospital death and 90-day outcomes in non-HIV-PCP patients with respiratory failure (RF).MethodsThis was a single center retrospective study in a tertiary care institution over 15 years. It included all adults inpatients (≥18 years old) with laboratory confirmed non-HIV-PCP with RF who were discharged or died from Peking University First Hospital between April 1st, 2007 and November 1st, 2022. Epidemiological, clinical, laboratory, imaging and outcome data were collected from patient records.ResultsIn this study, a total of 146 non-HIV-PCP patients with RF were included. There were 57 patients (39%) died during hospitalization, 44 patients (53%) died in Intensive care unit (ICU). A total of 137 patients completed 90 days of follow-up, of which 58 (42.3%) died. The multivariable regression analysis revealed that a CD8+ T cell count <115/μl (P=0.009), bronchoalveolar lavage fluid (BALF)-neutrophil percentage ≥50% (P=0.047), the time from corticosteroids withdrawal to symptom onset ≤5 days (P=0.012), and the time from visit to initiation of sulfonamides ≥2 days (P=0.011) were independent risk factors for in-hospital death. Furthermore, a CD8+ T cell count < 115/μl (P=0.001) and the time from visit to initiation of sulfonamides therapy ≥2 days (P=0.033) was independently associated with 90-day all-cause death.ConclusionsA low CD8+ T cell count in peripheral blood, a high percentage of BALF-neutrophils, a short time from corticosteroids withdrawal to symptom onset, and a long time from visit to initiation of sulfonamides are associated with poor prognosis in non-HIV-PCP patients with RF.

Objectives Frailty is a common and important concern of the ageing population. This study examined the association between the frailty index and negative outcomes of hospitalised elderly Chinese patients.Design Retrospective cohort study.Setting Geriatrics Department of Peking University First Hospital.Participants 470 hospitalised elderly patients.Main outcomes and measures Frailty was measured using a 30-item deficit-accumulation frailty index. The outcomes were the hospitalisation duration and readmission.Results The frailty index was available for 470 patients: 72 (15.32%) were categorised as robust, 272 (57.87%) as prefrail and 126 (26.81%) as frail. The frail group had a longer hospital stay than the robust and prefrail groups. After adjustment for age, sex and cause of hospitalisation at baseline, frailty remained a strong independent risk factor for all-cause readmission and cardiocerebrovascular disease readmission (HR 2.41, 95% CI 1.49 to 3.91, p<0.001; HR 4.92, 95% CI 1.47 to 6.31, p<0.001, respectively).Conclusions The frailty index predicted a longer length of stay and higher all-cause and cardiocerebrovascular disease readmission risk in hospitalised elderly patients.

Immune checkpoint inhibitors (ICIs) greatly improved outcomes of stage IV non-small cell lung cancer (NSCLC) in randomized clinical trials. Limited data exists regarding the survival improvement of ICI use at the population level. Clinical data of patients with pathologically confirmed stage IV NSCLC diagnosed in 2013 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were compared before and after ICI use to assess the survival improvement in the immunotherapy era in the real world. A total of 19,433 patients with stage IV NSCLC were included. Being female, age < 60 years, of American Indian and Asian or Pacific Islander race, married, non-squamous histology, without bone, brain, or liver metastases, and receiving chemotherapy were significantly associated with better prognosis in multivariable analyses. Propensity score matching (PSM) based on associated factors resulted in 8743 patients each in the non-immunotherapy and immunotherapy groups (1:1 ratio). After PSM, both overall survival (OS) (p < 0.001) and cancer-specific survival (CSS) (p < 0.001) were significantly improved in the immunotherapy group. The median OS (mOS) was 6.0 months in the non-immunotherapy group and 8.0 months in the immunotherapy group. The 1-, 2-, and 3-year OS rate was 29.0

Purpose: Hospital-acquired pneumonia (HAP) caused by carbapenem-resistant K. pneumoniae (CRKP), especially in elderly patients, results in high morbidity and mortality. Studies on risk factors, mortality, and antimicrobial susceptibility of CRKP pulmonary infection among elderly patients are lacking. Patients andMethods: A retrospective case-control study was conducted from January 2019 to December 2021. The elderly inpatients (>= 65 years) who were diagnosed with HAP caused by K. pneumoniae were enrolled. Clinical data were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors. Propensity score matching was used to minimize the effect of potential confounding variables. Kaplan-Meier analysis was used to compare survival.Results: A total of 115 patients with CRKP infection and 78 patients with carbapenem-susceptible K. pneumoniae (CSKP) infection were recruited. There were four independent risk factors for CRKP infection: history of intensive care unit (ICU) stays from hospital admission to positive respiratory specimen culture for K. pneumoniae (odds ratio (OR)=2.530), Charlson comorbidity index score >3 (OR = 2.420), prior exposure to carbapenems (OR = 5.280), and prior K. pneumoniae infection or colonization in the preceding 3 years (OR = 18.529). The all-cause 30-day mortality was 22.3%, the mortality of CRKP and CSKP infection was 28.7% and 12.8%, respectively. Independent risk factors for mortality included: older age (OR = 1.107), immunocompromised patients (OR = 8.632), severe pneumonia (OR = 51.244), quick Sepsis-related Organ Failure Assessment (qSOFA) score >= 2 (OR = 6.187), exposure to tigecycline before infection (OR = 24.702), and prolonged ICU stay (OR = 0.987). Thirty-day mortality was significantly lower in patients receiving ceftazidime-avibactam (CAZ-AVI) containing regimens than patients receiving polymyxin B sulfate (PB) containing regimens (P = 0.048). qSOFA score had a good prognostic effect [area under receiver operating characteristic curve (AUROC) of 0.838].Conclusion: Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. SARS-CoV-2 infection can induce secondary HLH, as described in previous case reports, but diagnosis and treatment are challenging.Case Study: We described an older male patient diagnosed with HLH related to previous SARS-CoV-2 infection. Fever was the only clinical manifestation initially but deterioration in clinical condition and laboratory parameters was observed during hospitalization. He responded poorly to classical therapy but was successfully treated with ruxolitinib.Conclusion: Clinicians should be aware of the possibility of HLH secondary to mild SARS-CoV-2 infection and take timely ther-apeutic measures to inhibit an inflammatory factor storm. Ruxolitinib is a potential choice for COVID-19 related HLH.

The hypoxia-inducible factor-1α/endoplasmic reticulum stress signaling pathway (HIF-1α/ERS) has a crucial role in the pathogenetic mechanism of pulmonary fibrosis (PF). However, the upstream regulatory mediators of this pathway remain unclear. In the present study, by conducting bioinformatics analysis, we found that Krüppel-like factor 4 (KLF4) expression was decreased in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF) as compared to that in patients with non-IPF. Furthermore, KLF4 expression was significantly reduced (p = 0.0331) in bleomycin-induced fibrotic HFL-1 cells. Moreover, in mice with bleomycin-induced PF, the degree of fibrosis was significantly reduced in mice overexpressing KLF4 as compared to that in wild-type mice. In mice and HFL-1 cells, KLF4 overexpression significantly reduced bleomycin-induced protein expression of HIF-1α (p = 0.0027) and ERS markers, particularly p-IRE1α (p = 0.0255) and ATF6 (p = 0.0002). By using the JASPAR database, we predicted that KLF4 has five binding sites for the HIF-1α promoter. The results of in vitro and in vivo studies suggest that KLF4 may inhibit PF through the HIF-1α/ERS pathway. This finding could guide the development of future therapies for PF and facilitate the identification of appropriate biomarkers for routine clinical diagnosis of PF.

BackgroundMost people are infected with COVID-19 during pandemics at the end of 2022. Older patients were more vulnerable. However, the incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection is not well described in elderly hospitalized COVID-19 patients.MethodsWe retrospectively reviewed the medical records of all elderly (≥65 years) hospitalized patients with laboratory-confirmed COVID-19 from December 1, 2022 to January 31, 2023. Demographics, underlying diseases, treatments, and laboratory data were collected. Univariate and multivariate logistic regression models were used to explore the risk factors associated with secondary bacterial, fungal or viral pulmonary infection and co-infection.ResultsA total of 322 older patients with COVID-19 were enrolled. The incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection was 27.3% (88/322) and 7.5% (24/322), respectively. The overall in-hospital mortality of all patients was 32.9% (106/322), and the in-hospital mortality among patients who acquired with secondary pulmonary infection and co-infection was 57.0% (57/100). A total of 23.9% (77/322) of patients were admitted to ICU within 48 h of hospitalization. The incidence of secondary pulmonary infection and co-infection among patients admitted to the ICU was 50.6% (39/77) and 13.0% (10/77), respectively. The overall in-hospital mortality of ICU patients was 48.1% (37/77), and the in-hospital mortality of ICU patients acquired with secondary pulmonary infection and co-infection was 61.4% (27/44). A total of 83.5% (269/322) of the included patients received empirical antibiotic therapy before positive Clinical Microbiology results. Influenza A virus (the vast majority were the H3N2 subtype) was the most common community acquired pathogen for co-infection. While A. baumannii, K. pneumoniae, and P. aeruginosa were the common hospital acquired pathogens for co-infection and secondary pulmonary infection. The incidence of Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections was high, and the mortality reached 76.9%. Predictors of secondary pulmonary infection and co-infection were ICU admission within 48 h of hospitalization, cerebrovascular diseases, critical COVID-19, and PCT > 0.5 ng/mL.ConclusionThe prognosis for elderly hospitalized COVID-19 patients with secondary pulmonary infection or co-infection is poor. The inflammatory biomarker PCT > 0.5 ng/mL played an important role in the early prediction of secondary pulmonary infection and co-infection in COVID-19 patients.

Objective: To analyze the bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis. Methods: Clinical data of patients with pulmonary mucormycosis undergoing bronchoscopy and interventional therapy in 4 tertiary general hospitals in China from May 2006 to May 2022 were retrospectively analyzed and the literature on the subject were reviewed. Results: The data of 10 patients with pathologically diagnosed pulmonary mucormycosis undergoing bronchoscopy and interventional therapy were collected, including 8 males and 2 females. The patients' age ranged from 21 to 72 (44±15) years. The underlying diseases included 6 cases of diabetes ketoacidosis, 3 cases of leukemia, 1 case after operation of lung cancer. Bronchoscopy showed that white viscous necrotic matters grew along the airway and blocked the airway in 9 cases, accompanied by airway bleeding in 3 cases, bloody secretion blocked the airway in 1 case, and bronchopulmonary cavity fistula in 2 cases. The biopsy histopathology of white necrotic matters showed that many mucor filaments were tangled together which were named mucormycelium. Among the 10 patients, 9 were treated with systemic drugs, including intravenous application of amphotericin B deoxycholate in 5 cases, intravenous application of amphotericin B liposome in 4 cases, oral posaconazole in 6 cases and intravenous injection in 1 case. Local drug therapy included aerosol inhalation of amphotericin B deoxycholate in 8 cases and local perfusion under bronchoscope in 5 cases. Bronchoscopic interventional therapy was used to remove mucormycelium in the bronchus, including cryotherapy in 8 cases, biopsy forceps in 7 cases, snare treatment in 2 cases and foreign body forceps in 2 cases. All 10 patients were clinical cured and with no death. Conclusions: Pulmonary mucormycosis is more common in immunocompromised hosts. Bronchoscopy often showed mucormycelium blocking the airway. Systemic and local drug therapy combined with bronchoscopic interventional therapy can achieve good clinical efficacy.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with an unclear pathogenesis. This study aimed to elucidate the function and potential mechanisms of TUG1 in IPF progression. Cell viability and migration were detected by CCK-8 and transwell assays. Autophagy, fibrosis, or EMT-related proteins were measured by Western blotting. Pro-inflammatory cytokine levels were assessed by ELISA kits. The subcellular localization of TUG1 was observed by FISH assay. RIP assay detected the interaction between TUG1 and CDC27. TUG1 and CDC27 was up-regulated in TGF-β1-induced RLE-6TN cells. TUG1 depletion suppressed pulmonary fibrosis via attenuating inflammation, EMT, inducing autophagy and inactivating PI3K/Akt/mTOR pathway in vitro and in vivo. TUG1 knockdown prevented CDC27 expression. TUG1 silencing ameliorated pulmonary fibrosis by reducing CDC27 expression and inhibiting PI3K/Akt/mTOR pathway.

Community acquired pneumonia(CAP)is characterized by high morbidity and mortality in immunocompromised patients, with the elderly as the main vulnerable population.However, current guidelines in China and elsewhere do not offer specific recommendations on the diagnosis and treatment of such patients.This paper reviews the definition, classification, epidemiology, etiological characteristics, clinical manifestations, diagnosis, treatment and prognosis of CAP in immunocompromised elderly patients, to provide a theoretical framework for its diagnosis and treatment and for the formulation of guidelines.