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Mycoplasma genitalium in pregnancy, including specific co-infections, is associated with lower birthweight: A prospective cohort study. 妊娠期生殖器支原体(包括特定的合并感染)与出生体重降低有关:一项前瞻性队列研究。
IF 12.8
Med Pub Date : 2024-09-13 Epub Date: 2024-06-12 DOI: 10.1016/j.medj.2024.05.007
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
{"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":null,"pages":null},"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}
引用次数: 0
Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial. Camrelizumab 联合化疗治疗未经治疗的晚期或转移性食管鳞状细胞癌的最终分析:ESCORT-1st 试验。
IF 12.8
Med Pub Date : 2024-09-13 Epub Date: 2024-06-12 DOI: 10.1016/j.medj.2024.05.008
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
{"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/m<sup>2</sup>) and cisplatin (75 mg/m<sup>2</sup>). 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":null,"pages":null},"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}
引用次数: 0
First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial. 转移性结直肠癌的一线舍普利单抗:随机、双盲、2/3 期试验的第 2 阶段结果。
IF 12.8
Med Pub Date : 2024-09-13 Epub Date: 2024-06-12 DOI: 10.1016/j.medj.2024.05.009
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
{"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":null,"pages":null},"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}
引用次数: 0
SMIM1 absence is associated with reduced energy expenditure and excess weight. SMIM1 的缺失与能量消耗减少和体重超标有关。
IF 12.8
Med Pub Date : 2024-09-13 Epub Date: 2024-06-20 DOI: 10.1016/j.medj.2024.05.015
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
{"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<sup>-/-</sup> 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":null,"pages":null},"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}
引用次数: 0
Q&A with Daniel Drucker. 丹尼尔-德鲁克问答。
IF 12.8
Med Pub Date : 2024-09-13 DOI: 10.1016/j.medj.2024.07.011
Daniel Drucker
{"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":null,"pages":null},"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}
引用次数: 0
Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease. 系统分析支持中国胃肠疾病临床实践指南的证据水平。
IF 12.8
Med Pub Date : 2024-09-13 Epub Date: 2024-06-17 DOI: 10.1016/j.medj.2024.05.006
Ke Han, Pengyue Zhao, Shimin Chen, Yinghui Bao, Boyan Li, Jiajun Du, Junwei Wu, Huikai Li, Ningli Chai, Xiaohui Du, Enqiang Linghu, Miao Liu
{"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":null,"pages":null},"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}
引用次数: 0
Immune checkpoint inhibitors for first-line treatment of advanced esophageal squamous cell carcinoma. 免疫检查点抑制剂用于晚期食管鳞状细胞癌的一线治疗。
IF 12.8
Med Pub Date : 2024-09-13 DOI: 10.1016/j.medj.2024.05.016
Maria Alsina, Tania Fleitas-Kanonnikoff
{"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.<sup>1</sup>.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"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}
引用次数: 0
Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients. 囊性纤维化患者接受雾化噬菌体疗法后产生的中和抗体。
IF 12.8
Med Pub Date : 2024-09-13 Epub Date: 2024-06-24 DOI: 10.1016/j.medj.2024.05.017
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
{"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":null,"pages":null},"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}
引用次数: 0
Shaping the future of heart health. 塑造心脏健康的未来。
IF 12.8
Med Pub Date : 2024-09-13 DOI: 10.1016/j.medj.2024.08.002
Alice Y Y Cheng, Shuyang Zhang, Stephan von Haehling, Milind Desai
{"title":"Shaping the future of heart health.","authors":"Alice Y Y Cheng, Shuyang Zhang, Stephan von Haehling, Milind Desai","doi":"10.1016/j.medj.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.medj.2024.08.002","url":null,"abstract":"<p><p>For World Heart Day on September 24, 2024, the World Heart Federation urges nations to endorse national strategies for enhancing cardiovascular health. While advancements show promise in reducing atherosclerosis, addressing healthcare inequalities and ensuring equitable access to tools remain crucial. This collection of voices touches on the intricate relationship between type 2 diabetes and cardiovascular disease, highlights innovative treatments for rare cardiomyopathies and heart failure, and explores the potentially transformative role of artificial intelligence in cardiovascular medicine, showcasing the dedication and innovation that are shaping the future of heart health.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297070","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}
引用次数: 0
How to rescue a DreaMM deferred …. 如何挽救 DreaMM 延期的 ....
IF 12.8
Med Pub Date : 2024-09-13 DOI: 10.1016/j.medj.2024.07.027
Nisha S Joseph, Sagar Lonial
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