A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer.

BACKGROUND: Cadonilimab is a bispecific antibody that simultaneously targets programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4. This study aimed to assess the safety and efficacy of cadonilimab plus anlotinib for the first-line treatment of advanced non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK/ROS1 mutations. METHODS: Patients received cadonilimab 15 mg/kg and 10 mg/kg every three weeks (Q3W) plus anlotinib at doses of 10 or 12 mg once daily for two weeks on a one-week-off schedule. The primary endpoints included safety and objective response rate (ORR). RESULTS: Sixty-nine treatment-naïve patients received cadonilimab 15 mg/kg Q3W combination (n = 49) and 10 mg/kg Q3W combination (n = 20). Treatment-related adverse events (TRAEs) were reported in 48 (98.0%) and 19 (95.0%) patients, with grade ≥3 TRAEs occurring in 29 (59.2%) and five (25.0%) patients, respectively. TRAEs leading to cadonilimab discontinuation occurred in eight (16.3%) and one (5.0%) patients in the cadonilimab 15 mg/kg Q3W and 10 mg/kg Q3W dosing groups. The confirmed ORRs were 51.0% (25/49) and 60.0% (12/20) accordingly. CONCLUSIONS: Cadonilimab 10 mg/kg Q3W plus anlotinib showed manageable safety and promising efficacy as a first-line chemo-free treatment for advanced NSCLC. GOV IDENTIFIER: NCT04646330.

Joint associations of air pollutants during pregnancy, infancy, and childhood with childhood persistent asthma: Nationwide database study in Japan.

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02-1.05; p<0.001), 1.02 (95 % CI: 1.01-1.03; p<0.001), and 1.03 (95 % CI: 1.01-1.04; p<0.001), respectively. Moreover, particulate matter with an aerodynamic diameter ≤ 2.5 µm was assigned the highest weight across all three exposure periods. Relatively high weights were assigned to suspended particulate matter and photochemical oxidants during pregnancy, carbon monoxide during infancy, and photochemical oxidants during childhood. Our study showed that a mixture of low-level air pollutants has a detrimental association with childhood persistent asthma.

Follow-Up Duration of Echocardiography in Patients with Kawasaki Disease with No Initial Coronary Aneurysms.

OBJECTIVE: To evaluate the optimal duration of echocardiographic follow-up in patients with Kawasaki disease without an initial coronary aneurysm. STUDY DESIGN: In this single-center, retrospective, observational study, we reviewed the results of follow-up echocardiography in children with Kawasaki disease enrolled in the Prospective Observational Study on Stratified Treatment with Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease from a children's hospital. The main enrollment criterion was the absence of coronary aneurysms, defined as a maximum z-score (Zmax) ≥2.5, in the proximal right coronary artery and the proximal left anterior descending artery within 9 days from treatment initiation. The primary outcome was Zmax on follow-up echocardiography at up to 5 years. RESULTS: Among 386 patients, 106 (27.5%) received prednisolone with intravenous immunoglobulin for first-line therapy, and 57 (14.8%) showed a poor response. Echocardiography at 1 month detected 9 patients with a Zmax ≥2, including 3 (0.8%) with coronary aneurysms requiring additional antithrombotic treatment and observation. Of 7 patients (1.8%) with normal echocardiographic findings at 1 month but a Zmax ≥2 later, 2 were lost to follow-up and 5 experienced spontaneous resolution, but none of the 7 patients required any change in management. CONCLUSIONS: The optimal duration of echocardiographic follow-up may be 1 month in patients with no initial coronary aneurysms and a Zmax <2 at 1 month. Coronary artery abnormalities observed after 1 month are rare and mostly benign in this category of patients.

Efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen for prevention of seizure recurrence during the same fever episode in children with suspected simple febrile seizures.

OBJECTIVE: This study was undertaken to evaluate the efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen in comparison with as-needed acetaminophen alone for prevention of seizure recurrence during the same fever episode in suspected pediatric simple febrile seizures (SFS). METHODS: This single-center, prospective, observational study was conducted from July 29, 2019 to February 15, 2021 at a children's hospital. Children aged 6 months to 60 months presenting to the emergency department with suspected SFS were included. Participants receiving both diazepam suppositories and as-needed acetaminophen were compared with those receiving as-needed acetaminophen alone. The primary outcome was seizure recurrence during the same fever episode. The secondary outcomes included the incidence of central nervous system (CNS) pathologies, adverse events, and medical costs. RESULTS: Of the 316 participants, 228 (72.2%) had their first febrile seizure. Diazepam (.3-.5 mg/kg for up to two doses) was administered to 88 of 316 patients (27.8%). The outcomes were available for 306 patients. The recurrence rate was 3.5% (3/85) in the patients receiving diazepam with as-needed acetaminophen and 12.2% (27/221) in the patients receiving as-needed acetaminophen alone (relative risk = .29, 95% confidence interval [CI] = .09-.93, p = .03). The adjusted odds ratio of diazepam administration against recurrence was .23 (95% CI = .07-.78, p = .02). None of the patients had a CNS pathology. No severe adverse events occurred, although mild ataxia was observed significantly more often in the patients receiving diazepam and as-needed acetaminophen (29.4% vs. 18.7%, p = .04). The median medical cost was US $199 (interquartile range [IQR] = 86-244) for the group receiving both medications and US $202 (IQR = 114-242) for the group receiving as-needed acetaminophen alone. SIGNIFICANCE: Compared with as-needed acetaminophen alone, diazepam with as-needed acetaminophen may reduce seizure recurrence more during the same fever episode without severe adverse events or additional costs in children with suspected SFS.

Metagenomic analysis and nitrogen removal performance evaluation of activated sludge from a sequencing batch reactor under different salinities.

The effect of salinity on the nitrogen removal performance and microbial community of activated sludge was investigated in a sequencing batch reactor. The NH4+-N removal efficiency was over 95% at 0-4% salinity, indicating that the nitrification performance of activated sludge was slightly affected by lower salinity. The obvious nitrite accumulation was observed with the increment of the salinity to 5%, followed by a notable decline in the nitrogen removal performance at 6% salinity. The salinity inhibited the microbial activity, and the specific rate of nitrification and denitrification was decreased by the increasing salinity obviously. Additionally, the lower activity of superoxide dismutase and peroxidase and higher reactive oxygen species content in activated sludge might account for the deteriorative nitrogen removal performance at 6% salinity. Metagenomics analysis revealed that the genes encoding the ABC-type quaternary amine transporter in the ABC transporter pathway were abundant in the activated sludge at 2% and 4% salinity, and the higher salinity of 6% led to the loss of the genes encoding the p-type Na+ transporter in the ABC transporter pathway. These results indicated that the salinity could weaken the ABC transporter pathway for the balance of osmotic pressure in activated sludge. The microbial activity and nitrogen removal performance of activated sludge were decreased due to the unbalanced osmotic pressure at higher salinity.

Impact of carbon/nitrogen ratio on the performance and microbial community of sequencing batch biofilm reactor treating synthetic mariculture wastewater.

The differences of cultured organism species, aquaculture model and supervisor mode lead to different carbon/nitrogen ratios in mariculture wastewater. Therefore, the performance, microbial community and enzymatic activity of sequencing batch biofilm reactor were compared in treating synthetic mariculture wastewater at different chemical oxygen demand/nitrogen (COD/N) ratios. Compared with COD/N ratio of 6, the ammonia-oxidizing rate and nitrite-oxidizing rate at COD/N ratio of 5, 4 and 3 increased by 3.66 % and 3.08 %, 11.19 % and 14.95 %, and 24.50 % and 32.54 %, respectively. Similarly, the ammonia monooxygenase and nitrite oxidoreductase activities increased by 3.50 % and 6.76 %, 11.09 % and 16.22 %, and 25.43 % and 39.19 % at COD/N ratio at 5, 4 and 3, respectively. However, the denitrifying rate and denitrification enzymatic activity declined with the decrease of C/N ratio from 6 to 3. The production, protein content and polysaccharide content of loosely bound extracellular polymeric substances (LB-EPS) and tightly bound EPS (TB-EPS) reduced with the decrease of COD/N ratio from 6 to 3. The abundance of nitrifying genera increased with the decrease of COD/N ratio from 6 to 3, whereas most of denitrification genera displayed a decreasing trend. The microbial co-occurrence pattern, keystone taxa and significant difference were altered with the decrease of COD/N ratio. Among the keystone taxa, Thauera, Denitromonas, Nitrosomonas and Denitratisoma had a close link with nitrogen transformation. The present results can provide some theoretical basis for evaluating the effect of carbon/nitrogen ratio on the nitrogen removal of biological wastewater treatment systems.

Insight into the fate of antibiotic resistance genes and bacterial community in co-composting green tea residues with swine manure.

Green tea residues (GTRs) are byproducts of tea production and processing, and this type of agricultural waste retains nutritious components. This study investigated the co-composting of GTRs with swine manure, as well as the effects of GTRs on antibiotic resistance genes (ARGs) and the bacterial community during co-composting. The temperature and C/N ratio indicate compost was mature after processing. The addition of GTRs effectively promoted the reduction in the abundances of most targeted ARGs (tet and sul genes), mobile genetic element (MGE; intI1), and metal resistance genes (MRGs; pcoA and tcrB). Redundancy analysis (RDA) showed that GTRs can reduce the abundance of MRGs and ARGs by reducing the bioavailability of heavy metals. Network analysis shows that Firmicutes and Actinobacteria were the main hosts of ARGs and ARGs, MGEs, and MRGs shared the same potential host bacteria. Adding GTRs during composting may reduce ARGs transmission through horizontal gene transfer (HGT). GTRs affected the bacterial community, thereby influencing the variations in the ARG profiles and reducing the potential risk associated with the compost product.

Effect of light intensity on nitrogen transformation, enzymatic activity, antioxidant system and transcriptional response of Chlorella pyrenoidosa during treating mariculture wastewater.

The nitrogen transformation, enzymatic activity, antioxidant ability and transcriptional response of Chlorella pyrenoidosa (C. pyrenoidosa) treating mariculture wastewater were compared under different light intensities. The microalgal growth, chlorophyll synthesis and nitrogen removal ability of C. pyrenoidosa increased with the light intensity from 3000 to 7000 Lux, whereas they slightly decreased under 9000 and 11,000 Lux. The nitrogen metabolism enzymatic activities displayed obvious differences under different light intensities and affected the nitrogen transformation process. The reactive oxygen species (ROS) production increased with the increase of operational time, whereas it had distinct differences under different light intensities. The changes of antioxidant enzymatic activities were positively correlated with the ROS production. The transcriptional response of C. pyrenoidosa was in accordance with the variation of the photosynthesis, nitrogen assimilation and antioxidant system under different light intensities. This study provides theoretical basis and technical support to select suitable light intensity for algae treating mariculture wastewater.

Performance evaluation and metagenomic analysis of sequencing batch reactor under transient 2,4,6-trichlorophenol shock.

The transient chlorophenol shock under some emergency conditions might directly affect the pollutant removal of bioreactor. Therefore, the recovery of bioreactor performance after transient chlorophenol shock is a noteworthy issue. In the present research, the performance, antioxidant response, microbial succession and functional genes of sequencing batch reactor (SBR) were evaluated under transient 2,4,6-trichlorophenol (2,4,6-TCP) shock. The chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N) removal efficiencies decreased sharply in the first 4 days after 60 mg/L 2,4,6-TCP shock for 24 h and gradually recovered to normal in the subsequent 8 days. The nitrogen removal rates and their corresponding enzymatic activities rapidly decreased after transient 2,4,6-TCP shock and then gradually increased to normal. The increase of antioxidant enzymatic activity, Cu-Zn SOD genes and Fe-Mn SOD genes contributed to the recovery of SBR performance. The abundance of genes encoding ammonia monooxygenase and hydroxylamine dehydrogenase decreased after transient 2,4,6-TCP shock, including amoA, amoC and nxrA. Thauera, Dechloromonas and Candidatus_Competibacter played key roles in the restorative process, which provided stable abundances of narG, norB , norC and nosZ. The results will deeply understand into the effect of transient 2,4,6-TCP shock on bioreactor performance and provide theoretical basis to build promising recoveries strategy of bioreactor performance.

Camrelizumab combined with apatinib and nanoparticle albumin-bound paclitaxel in lung adenocarcinoma (CAPAP-lung): a single-arm phase II study.

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Findings: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. Interpretation: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Funding: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).

Anlotinib plus docetaxel vs. docetaxel alone for advanced non-small-cell lung cancer patients who failed first-line treatment: A multicenter, randomized phase II trial.

OBJECTIVES: Given the modest efficacy of docetaxel in advanced non-small cell lung cancer (NSCLC), this study assesses the therapeutic potential and safety profile of anlotinib in combination with docetaxel compared to docetaxel monotherapy as a second-line therapy for patients with advanced NSCLC. MATERIALS AND METHODS: In this phase II study, patients with advanced NSCLC experiencing failure with first-line platinum-based regimens were randomized in a 1:1 ratio to receive either anlotinib plus docetaxel or docetaxel alone. Primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety as secondary endpoints. RESULTS: A total of 83 patients were randomized. The combination of anlotinib and docetaxel significantly extended median PFS to 4.4 months compared to 1.6 months for docetaxel alone (hazard ratio [HR] = 0.38, 95 % confidence interval [CI]: 0.23-0.63, P = 0.0002), and also demonstrated superior ORR (32.5 % vs. 9.3 %, P = 0.0089) and DCR (87.5 % vs. 53.5 %, P = 0.0007). Median OS was observed at 12.0 months in the combination group vs. 10.9 months in the monotherapy group (HR = 0.82, 95 % CI: 0.47-1.43, P = 0.4803). For patients previously treated with immunotherapy, the median PFS was notably longer at 7.8 vs. 1.7 months (HR = 0.22, 95 % CI: 0.09-0.51, P = 0.0290). The incidence of grade ≥ 3 treatment-related adverse events, predominantly leukopenia (15.0 % vs. 7.0 %) and neutropenia (10.0 % vs. 5.0 %), was manageable across both groups. CONCLUSION: Anlotinib plus docetaxel offers a viable therapeutic alternative for patients with advanced NSCLC who failed first-line platinum-based treatments.

Global transportation infrastructure exposure to the change of precipitation in a warmer world.

Transportation infrastructures are generally designed to have multi-decadal service lives. Transport infrastructure design, however, is largely based on historical conditions. Yet, in the face of global warming, we are likely going to experience more intense and frequent extreme events, which may put infrastructure at severe risk. In this study, we comprehensively analyze the exposure of road and railway infrastructure assets to changes in precipitation return periods globally. Under ~2 degrees of warming in mid-century (RCP 8.5 scenario), 43.6% of the global transportation assets are expected to experience at least a 25% decrease in design return period of extreme rainfall (a 33% increase in exceedance probability), which may increase to 69.9% under ~4 degrees of warming by late-21st century. To accommodate for such increases, we propose to incorporate a safety factor for climate change adaptation during the transportation infrastructure design process to ensure transportation assets will maintain their designed risk level in the future. Our results show that a safety factor of 1.2 would work sufficient for most regions of the world for quick design process calculations following the RCP4.5 path.

Impact of aerobic/anoxic alternation number on performance, microbial community and functional genes of sequencing batch biofilm reactor treating mariculture wastewater.

The performance, microbial community and functional genes of a sequencing batch biofilm reactor (SBBR) were investigated in treating mariculture wastewater under different aerobic/anoxic alternation number. The removal efficiency of chemical oxygen demand (COD) and NH4+-N kept at 95.66 ± 1.83 % and 90.28 ± 2.42 % under aerobic/anoxic alternation number between 1 and 4. The total nitrogen (TN) removal efficiency gradually decreased from 94.45 ± 1.12 % to 83.06 ± 1.25 % with the increase of aerobic/anoxic alternative number from 1 to 4. The nitrification rates and their corresponding enzymatic activities increased slightly with the increase of aerobic/anoxic alternation number, whereas the denitrifying process had the contrary results. The variation of aerobic/anoxic alternation number obviously affected the microbial diversity and abundance. The microbial network structure and keystone taxa were different under different aerobic/anoxic alternation number. The functional genes abundance for the denitrification pathway decreased with the increase of aerobic/anoxic alternation number.

Comparative evaluation of four Chlorella species treating mariculture wastewater under different photoperiods: Nitrogen removal performance, enzyme activity, and antioxidant response.

The nitrogen removal performance, nitrogen metabolism enzyme activities, and antioxidant response of four Chlorella species (Chlorella sp., Chlorella vulgaris, Chlorella sorokiniana, and Chlorella protothecoides) were compared under different light: dark (L:D) photoperiods during treating mariculture wastewater. The increase of light duration in the range of 8L:16D to 16L:8D was beneficial to the chlorophyll synthesis of selected four Chlorella species. Chlorella vulgaris was the most effective to treat mariculture wastewater than Chlorella sp., Chlorella sorokiniana, and Chlorella protothecoides. and its microalgae density, photosynthetic activity, and nitrogen metabolism enzyme activity were higher than those of the other three Chlorella species. An obvious oxidative stress in microalgal cells was under 20L:4D photoperiod, which led to a decrease in photosynthetic activity and nitrogen metabolizing enzyme activity. Among the four Chlorella species, Chlorella protothecoides had the highest degree of light-induced stress and ROS accumulation. This study can provide suitable microalgae and optimal photoperiod for treating mariculture wastewater.

Performance evaluation, enzymatic activity change and metagenomic analysis of sequencing batch reactor under divalent zinc stress.

Divalent zinc (Zn2+) are widely detected in domestic and industrial wastewater, and it is essential to evaluate the effect of Zn2+ on wastewater biological treatment process due to its bio-toxicity. In this study, the nitrogen removal rates and their corresponding enzymatic activities of sequencing batch reactor decreased with the increase of Zn2+ concentration. The Zn2+ accumulation in activated sludge caused significant antioxidant response, and the reactive oxygen species (ROS) production and antioxidant enzymatic activities were positively correlated with Zn2+ concentration. The presence of Zn2+ inhibited the metabolic pathways related to energy production and electron transport. The abundance decreases of nitrification and denitrification functional genes led to the deterioration of nitrogen removal performance under Zn2+ stress. The correlation analysis between functional gene modules and microbial genera revealed that Zoogloea had obvious Zn2+ resistance. This study can provide the insights into the influencing mechanism of Zn2+ on the biological nitrogen removal process.

Platymonas helgolandica-driven nitrogen removal from mariculture wastewater under different photoperiods: Performance evaluation, enzyme activity and transcriptional response.

The nitrogen removal performance and biological mechanism of Platymonas helgolandica var. Tsingtaoensis (P. helgolandica) were investigated in treating mariculture wastewater under different light: dark (L:D) photoperiods. The growth of P. helgolandica was positively correlated with the photoperiods from 6L:18D to 15L:9D, and the highest photosynthetic activity appeared under 6L:18D photoperiod on day 3. P. helgolandica exhibited the highest removal efficiencies of total nitrogen and COD at 89 % and 93 % under 15L:9D photoperiod, respectively. NH4+-N assimilation was proportional to the photoperiods from 6L:18D to 15L:9D and longer illumination promoted NO2--N removal. However, the highest NO3--N reduction rate was achieved under 12L:12D photoperiod. The different nitrogen-transformed enzymatic activities were affected by photoperiod. Transcriptome revealed that unigenes were enriched in nitrogen metabolism and photosynthesis pathways, of which the functional gene expression was up-regulated significantly. This study provides insights into the optimization of photoperiod for mariculture wastewater treatment by P. helgolandica.

Rh-endostatin plus camrelizumab and chemotherapy in first-line treatment of advanced non-small cell lung cancer: A multicenter retrospective study.

BACKGROUND: Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non-small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh-endostatin), an antiangiogenic drug, and camrelizumab, an anti-PD-1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh-endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC. METHODS: Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh-endostatin (70 mg/day, days 1-3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. RESULTS: Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow-up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23-13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment-related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed. CONCLUSION: Rh-endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients.

The efficacy and safety of immune checkpoint inhibitors combined with chemotherapy or anti-angiogenic therapy as a second-line or later treatment option for advanced non-small cell lung cancer: a retrospective comparative cohort study.

Background: Although immune checkpoint inhibitor (ICI) monotherapy remains the standard of second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) , the objective response rate (ORR) is low. There is an urgent need to increase the response population of second-line immunotherapy, and ICI combination therapy may be a possible option. However, the evidence is insufficient. Methods: We retrospectively collected the medical records of patients who received ICI monotherapy or ICI combination therapy as a second-line or later treatment option. We further analysed baseline clinical characteristics, evaluated treatment efficacy, assessed treatment-related adverse events (AEs) and followed up survival. The outcome variables assessed in the study were ORR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. Results: A total of 145 patients were ultimately enrolled in this study, including the ICI monotherapy group (n=63) and ICI combination therapy group (n=82). The ICI combination therapy group was further divided into the ICI/chemotherapy group (n=57) and ICI/anti-angiogenic therapy group (n=25). The baseline was comparable among the three subgroups. The ICI combination therapy groups showed a higher ORR (29.3% vs. 11.1%, P=0.008) and DCR (85.4% vs. 61.9%, P=0.001) and a longer PFS (6.77 vs. 3.47 months, P<0.001) and OS (18.60 vs. 8.47 months, P<0.001) than the ICI monotherapy group. The ICI/chemotherapy group showed a significantly higher ORR (31.6% vs. 11.1%, P=0.006) and DCR (84.2% vs. 61.9%, P=0.006) and a longer PFS (6.37 vs. 3.47 months, P<0.001) and OS (18.60 vs. 8.47 months, P<0.001) than the ICI monotherapy group. The ICI/anti-angiogenic therapy group showed a significantly higher DCR (88.0% vs. 61.9%, P=0.021) and a longer PFS (8.17 vs. 3.47 months, P<0.001) and OS (19.20 vs. 8.47 months, P=0.005) than the ICI monotherapy group. Neither of the combined ICI therapy groups showed a significant increase in the incidence of AEs compared to the ICI monotherapy group. Conclusions: ICI combined with chemotherapy or anti-angiogenic therapy as second-line or later treatment demonstrated superiority over ICI monotherapy in advanced NSCLC patients without prior immunotherapy. These results provide a potentially superior treatment strategy and require verification in prospective clinical trials.

Case Report: Tissue Origin Identification for Cancer of Unknown Primary: Gene Expression Profiling Approach.

The treatment of cancer of unknown primary (CUP) is a huge challenge for clinicians. Gene expression profiling can help identify the tissue origin of tumors by detecting the expression levels of specific genes in tumor tissues. Herein, we report four CUP cases. All of them have been successfully identified with the corresponding primary tumor sites through gene expression profiling analysis. Then all patients received accurate treatment, providing reference to guide therapeutic decisions to treat CUP tumors in the future.