Med最新文献

{"title":"Gut microbiome pattern impacts treatment response in primary biliary cholangitis.","authors":"Qiaoyan Liu, Bingyuan Huang, Yijun Zhou, Yiran Wei, Yikang Li, Bo Li, You Li, Jun Zhang, Qiwei Qian, Ruiling Chen, Zhuwan Lyu, Rui Wang, Qin Cao, Qun Xu, Qixia Wang, Qi Miao, Zhengrui You, Min Lian, Merrill Eric Gershwin, Qiaofei Jin, Xiao Xiao, Xiong Ma, Ruqi Tang","doi":"10.1016/j.medj.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.medj.2024.08.003","url":null,"abstract":"<p><strong>Background: </strong>Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease. An inadequate response to ursodeoxycholic acid (UDCA) poses a high risk of progression toward end-stage liver disease. Gut dysbiosis has been implicated in PBC. Here, we aimed to investigate microbial signatures that permit risk stratification and provide mechanistic insights into novel therapies for PBC.</p><p><strong>Methods: </strong>We prospectively recruited UDCA treatment-naive patients with PBC and performed metagenomic sequencing and metabolomic profiling using stool and serum samples obtained before (n = 132) and after (n = 59) treatment. PBC microbiome subtypes were identified using unsupervised machine learning methods and validated in two independent cohorts.</p><p><strong>Findings: </strong>PBC baseline metagenomes clustered into two community subtypes characterized by varying abundances of Clostridia taxa. Compared with Clostridia^low microbiomes, Clostridia^high microbiomes were more similar to healthy controls. Notably, patients in the Clostridia^low subtype exhibited a 2-fold higher UDCA non-response rate compared to those in the Clostridia^high subtype (41% vs. 20%, p = 0.015). Integrative analysis of metagenomic and metabolomic data revealed divergent functional modules and metabolic activities between the two metacommunities. In particular, anaerobic fermentation and the production of bioactive metabolites, including tryptophan derivatives and secondary bile acids, crucial for immune regulation and gut barrier maintenance, were markedly diminished in the Clostridia^low subtype. Moreover, UDCA administration reconfigured the fecal microbial and metabolic profiles only in the Clostridia^high group. Importantly, the microbiome subtypes and their associations with UDCA response were reproducible in two independent treatment-naive PBC cohorts.</p><p><strong>Conclusions: </strong>Characterizing baseline microbiota patterns may enable the prediction of treatment outcomes in PBC and facilitate personalized treatment strategies.</p><p><strong>Funding: </strong>This research was mainly supported by the National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exceptional, naturally occurring HIV-1 control: Insight into a functional cure.","authors":"María Salgado, Stephen A Migueles, Xu G Yu, Javier Martinez-Picado","doi":"10.1016/j.medj.2024.06.008","DOIUrl":"10.1016/j.medj.2024.06.008","url":null,"abstract":"<p><p>Exceptional elite controllers represent an extremely rare group of people with HIV-1 (PWH) who exhibit spontaneous, high-level control of viral replication below the limits of detection in sensitive clinical monitoring assays and without disease progression in the absence of antiretroviral therapy for prolonged periods, frequently exceeding 25 years. Here, we discuss the different cases that have been reported in the scientific literature, their unique genetic, virological, and immunological characteristics, and their relevance as the best model for the functional cure of HIV-1.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1071-1082"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.","authors":"Mingming He, Zhiqiang Wang, Jin Lu, Yuxian Bai, Teng Mao, Jun Wang, Qingxia Fan, Yiping Zhang, Kuaile Zhao, Zhendong Chen, Shegan Gao, Jiancheng Li, Zhichao Fu, Kangsheng Gu, Zhihua Liu, Lin Wu, Xiaodong Zhang, Jifeng Feng, Zuoxing Niu, Yi Ba, Helong Zhang, Ying Liu, Li Zhang, Xuhong Min, Jing Huang, Ying Cheng, Dong Wang, Zhen Sheng, Wanqin Zeng, Li Song, Rui-Hua Xu, Huiyan Luo","doi":"10.1016/j.medj.2024.05.008","DOIUrl":"10.1016/j.medj.2024.05.008","url":null,"abstract":"<p><strong>Background: </strong>The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS.</p><p><strong>Methods: </strong>Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m²) and cisplatin (75 mg/m²). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee.</p><p><strong>Findings: </strong>As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS.</p><p><strong>Conclusions: </strong>The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC.</p><p><strong>Funding: </strong>This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1137-1149.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial.","authors":"Zi-Xian Wang, Junjie Peng, Xinjun Liang, Ying Cheng, Yanhong Deng, Kehe Chen, Mingjun Zhang, Jingdong Zhang, Wei Wang, Bangwei Cao, Yongdong Jin, Meili Sun, Yuan Lin, Suxia Luo, Zhen Li, Liu Yang, Ying Ke, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Feng Wang, Rui-Hua Xu","doi":"10.1016/j.medj.2024.05.009","DOIUrl":"10.1016/j.medj.2024.05.009","url":null,"abstract":"<p><strong>Background: </strong>Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear.</p><p><strong>Methods: </strong>This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety.</p><p><strong>Findings: </strong>Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively.</p><p><strong>Conclusions: </strong>Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC.</p><p><strong>Funding: </strong>This work was funded by Shanghai Henlius Biotech, Inc.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1150-1163.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycoplasma genitalium in pregnancy, including specific co-infections, is associated with lower birthweight: A prospective cohort study.","authors":"Michelle J L Scoullar, Pele Melepia, Elizabeth Peach, Ruth Fidelis, Hadlee Supsup, Eliza M Davidson, Philippe Boeuf, Catriona S Bradshaw, Glenda Fehler, Priscah Hezeri, Dukduk Kabiu, Arthur Elijah, Peter M Siba, Elissa C Kennedy, Alexandra J Umbers, Leanne J Robinson, Andrew J Vallely, Steven G Badman, Lisa M Vallely, Freya J I Fowkes, Christopher J Morgan, William Pomat, Brendan S Crabb, James G Beeson","doi":"10.1016/j.medj.2024.05.007","DOIUrl":"10.1016/j.medj.2024.05.007","url":null,"abstract":"<p><strong>Background: </strong>Mycoplasma genitalium infection in pregnancy is increasingly reported at similar frequencies to other sexually transmitted infections (STIs). Knowledge on its contribution to adverse pregnancy outcomes is very limited, especially relative to other STIs or bacterial vaginosis (BV). Whether M. genitalium influences birthweight remains unanswered.</p><p><strong>Methods: </strong>Associations between birthweight and M. genitalium and other STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and BV in pregnancy were examined in 416 maternal-newborn pairs from a prospective cohort study in Papua New Guinea.</p><p><strong>Findings: </strong>Compared to uninfected women, M. genitalium (-166.9 g, 95% confidence interval [CI]: -324.2 to -9.7 g, p = 0.038) and N. gonorrhoeae (-274.7 g, 95% CI: -561.9 to 12.5 g, p = 0.061) infections were associated with lower birthweight in an adjusted analysis. The association for C. trachomatis was less clear, and T. vaginalis and BV were not associated with lower birthweight. STI prevalence was high for M. genitalium (13.9%), N. gonorrhoeae (5.0%), and C. trachomatis (20.0%); co-infections were frequent. Larger effect sizes on birthweight occurred with co-infections of M. genitalium, N. gonorrhoeae, and/or C. trachomatis.</p><p><strong>Conclusion: </strong>M. genitalium is a potential contributor to lower birthweight, and co-infections appear to have a greater negative impact on birthweight. Trials examining the impact of early diagnosis and treatment of M. genitalium and other STIs in pregnancy and preconception are urgently needed.</p><p><strong>Funding: </strong>Funding was received from philanthropic grants, the National Health and Medical Research Council, and the Burnet Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1123-1136.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMIM1 absence is associated with reduced energy expenditure and excess weight.","authors":"Luca Stefanucci, Camous Moslemi, Ana R Tomé, Samuel Virtue, Guillaume Bidault, Nicholas S Gleadall, Laura P E Watson, Jing E Kwa, Frances Burden, Samantha Farrow, Ji Chen, Urmo Võsa, Keith Burling, Lindsay Walker, John Ord, Peter Barker, James Warner, Amy Frary, Karola Renhstrom, Sofie E Ashford, Jo Piper, Gail Biggs, Wendy N Erber, Gary J Hoffman, Nadia Schoenmakers, Christian Erikstrup, Klaus Rieneck, Morten H Dziegiel, Henrik Ullum, Vian Azzu, Michele Vacca, Hugo Javier Aparicio, Qin Hui, Kelly Cho, Yan V Sun, Peter W Wilson, Omer A Bayraktar, Antonio Vidal-Puig, Sisse R Ostrowski, William J Astle, Martin L Olsson, Jill R Storry, Ole B Pedersen, Willem H Ouwehand, Krishna Chatterjee, Dragana Vuckovic, Mattia Frontini","doi":"10.1016/j.medj.2024.05.015","DOIUrl":"10.1016/j.medj.2024.05.015","url":null,"abstract":"<p><strong>Background: </strong>Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.</p><p><strong>Methods: </strong>We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1^-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.</p><p><strong>Findings: </strong>We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.</p><p><strong>Conclusion: </strong>This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.</p><p><strong>Funding: </strong>This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1083-1095.e6"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Q&A with Daniel Drucker.","authors":"Daniel Drucker","doi":"10.1016/j.medj.2024.07.011","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.011","url":null,"abstract":"<p><p>Med discusses the history and future of GLP-1 research with Professor Daniel Drucker from the Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, Canada.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 9","pages":"1031-1034"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitors for first-line treatment of advanced esophageal squamous cell carcinoma.","authors":"Maria Alsina, Tania Fleitas-Kanonnikoff","doi":"10.1016/j.medj.2024.05.016","DOIUrl":"https://doi.org/10.1016/j.medj.2024.05.016","url":null,"abstract":"<p><p>Immunotherapy has revolutionized the treatment landscape of esophageal squamous cell carcinoma. He et al. present the final results of the randomized phase 3 ESCORT-1st trial, confirming positive survival outcomes when adding the anti-PD1 inhibitor camrelizumab to first-line chemotherapy treatment in Chinese patients with esophageal squamous cell cancer.¹.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 9","pages":"1038-1040"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease.","authors":"Ke Han, Pengyue Zhao, Shimin Chen, Yinghui Bao, Boyan Li, Jiajun Du, Junwei Wu, Huikai Li, Ningli Chai, Xiaohui Du, Enqiang Linghu, Miao Liu","doi":"10.1016/j.medj.2024.05.006","DOIUrl":"10.1016/j.medj.2024.05.006","url":null,"abstract":"<p><strong>Background: </strong>Clinical practice guidelines (CPGs) inform healthcare decisions and improve patient care. However, an evaluation of guidelines on gastrointestinal diseases (GIDs) is lacking. This study aimed to systematically analyze the level of evidence (LOE) supporting Chinese CPGs for GIDs.</p><p><strong>Methods: </strong>CPGs for GIDs were identified by systematically searching major databases. Data on LOEs and classes of recommendations (CORs) were extracted. According to the Grades of Recommendation, Assessment, Development, and Evaluation system, LOEs were categorized as high, moderate, low, or very low, whereas CORs were classified as strong or weak. Statistical analyses were conducted to determine the distribution of LOEs and CORs across different subtopics and assess changes in evidence quality over time.</p><p><strong>Findings: </strong>Only 27.9% of these recommendations were supported by a high LOE, whereas approximately 70% were strong recommendations. There was a significant disparity among different subtopics in the proportion of strong recommendations supported by a high LOE. The number of guidelines has increased in the past 5 years, but there has been a concomitant decline in the proportion of recommendations supported by a high LOE.</p><p><strong>Conclusions: </strong>There is a general lack of high-quality evidence supporting Chinese CPGs for GIDs, and there are inconsistencies in strong recommendations that have not improved. This study identified areas requiring further research, emphasizing the need to bridge these gaps and promote the conduct of high-quality clinical trials.</p><p><strong>Funding: </strong>This study was supported by the National Key R&D Program of China (2022YFC2503604 and 2022YFC2503605) and Special Topics in Military Health Care (22BJZ25).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1112-1122.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients.","authors":"Mireia Bernabéu-Gimeno, Marco Pardo-Freire, Benjamin K Chan, Paul E Turner, Ana Gil-Brusola, Santiago Pérez-Tarazona, Laura Carrasco-Hernández, Esther Quintana-Gallego, Pilar Domingo-Calap","doi":"10.1016/j.medj.2024.05.017","DOIUrl":"10.1016/j.medj.2024.05.017","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration.</p><p><strong>Methods: </strong>Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored.</p><p><strong>Findings: </strong>Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy.</p><p><strong>Conclusions: </strong>Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation.</p><p><strong>Funding: </strong>This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1096-1111.e6"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}