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{"title":"Association between situs inversus and maternal SARS-CoV-2 infection at gestational age 4-6 weeks.","authors":"Zhenming Guo, Yingchun Luo, Yan Bi, Liangjie Liu, Yuan Qi, Jin Yan, Chunhai Cai, Chenxiang Xi, Yihan Tan, Shifa Yao, Yanhui Qu, Ping Chen, Jiayu Chen, Yanlin Wang, Xiao Mao, Baoying Ye, Shaorong Gao, Guang He, Shan Bian","doi":"10.1016/j.medj.2024.07.009","DOIUrl":"10.1016/j.medj.2024.07.009","url":null,"abstract":"<p><strong>Background: </strong>A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus.</p><p><strong>Methods: </strong>In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement. Relevant information, including SARS-CoV-2 infection, and other potential risk factors were collected. Conditional logistic regression was used to test possible associations between fetal situs inversus and SARS-CoV-2 infection at different gestational weeks as well as individual risk factors.</p><p><strong>Findings: </strong>A total of 52 pregnant women diagnosed with fetal situs inversus between January 1 and October 31, 2023 and 208 matched controls with normal fetuses were enrolled. We found no association between an increased risk of fetal situs inversus with gestational SARS-CoV-2 infection or with other risk factors. However, fetal situs inversus was significantly associated with SARS-CoV-2 infection specifically in gestational weeks 4-6 (adjusted odds ratio [aOR] 6.54 [95% confidence interval 1.76-24.34]), but not with infection at other gestational ages, after adjusting for covariates.</p><p><strong>Conclusions: </strong>Increased risk of fetal situs inversus is significantly associated with maternal SARS-CoV-2 infection at gestational weeks 4-6, corresponding to the fetal developmental window for visceral lateralization in humans.</p><p><strong>Funding: </strong>National Key R&D Program of China, etc.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879594","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":"Preoperative camrelizumab combined with chemotherapy for borderline resectable ESCC: A single-arm, prospective, phase 2 study.","authors":"Guoqing Zhang, Teng Mu, Yan Zhang, Jia Jiao, Zheng Ding, Hang Yang, Dabo Pan, Jia Zhao, Jindong Li, Xiangnan Li","doi":"10.1016/j.medj.2024.07.015","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.015","url":null,"abstract":"<p><strong>Background: </strong>We investigated the safety and efficacy of preoperative camrelizumab combined with chemotherapy for treating thoracic borderline resectable esophageal squamous cell carcinoma (Br-ESCC) (ChiCTR2200056728).</p><p><strong>Methods: </strong>Patients with thoracic Br-ESCC received intravenous camrelizumab plus chemotherapy and underwent esophagectomy. The primary endpoint was the pathologic complete response (pCR) rate. We introduced computed tomography and endoscopic examination into the diagnostic criteria to increase its reproducibility. Additionally, we defined a new resection status, Rbr^+/-, for Br-ESCC.</p><p><strong>Findings: </strong>Thirty-one patients with Br-ESCC were ultimately enrolled in this study. Overall, 71.0% (22/31) of the patients underwent esophagectomy. R0 resection was achieved in 81.8% of patients (18/22). pCR and major pathological response were observed in 40.9% (9/22) and 63.6% (14/22) of the resected patients, respectively. Eighteen R0 resection patients were redefined according to our Rbr definition; 61.1% (11/18) were classified as Rbr⁺ resection, and 38.9% (7/18) were classified as Rbr^- resection. With a median postoperative follow-up of 17.9 months, 4 patients out of 11 who underwent Rbr⁺ resection experienced local recurrence (2 of whom achieved pCR). However, no patients (0/7) who underwent Rbr^- resection experienced local recurrence.</p><p><strong>Conclusions: </strong>Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for Br-ESCC. R0 resection was achieved in 81.8% of patients, and a pCR was observed in 40.9% of resected patients. Even after complete excision, Rbr⁺ resection leads to a higher rate of local recurrence in patients with Br-ESCC.</p><p><strong>Funding: </strong>This study was supported by the Key Scientific Research Projects of the Institutions of Higher Learning in Henan Province (no. 21A320032).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914183","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":"A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma.","authors":"Kaiyang Ding, Hailing Liu, Haiyan Yang, Huayuan Zhu, Jie Ma, Hongling Peng, Hongming Huang, Wei Shi, Lei Cao, Wei Wu, Xiaoli Zhao, Xiao Shi, Jianyong Li, Xiaohui Zhang, Lei Fan","doi":"10.1016/j.medj.2024.07.007","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.007","url":null,"abstract":"<p><strong>Background: </strong>Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients.</p><p><strong>Methods: </strong>We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate.</p><p><strong>Findings: </strong>As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%).</p><p><strong>Conclusions: </strong>The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies.</p><p><strong>Funding: </strong>This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861129","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":"Tumor microenvironment RNA test to predict immunotherapy outcomes in advanced gastric cancer: The TIMES001 trial.","authors":"Min Shi, Dongqiang Zeng, Huiyan Luo, Jian Xiao, Yongqiang Li, Xia Yuan, Na Huang, Jiani Wu, Siting Zheng, Jianhua Wu, Shaowei Li, Xiaoxiang Rong, Chunlin Wang, Luyang Jiang, Qianqian Mao, Wenjun Qiu, Jian Guo, Qiong Deng, Huiying Sun, Xiansheng Lu, Yunfang Yu, Yonghong Lai, Yiran Fang, Rui Zhou, Ling Wang, Xiatong Huang, Yuyun Kong, Jun Li, Li Liang, Jianping Bin, Yulin Liao, Wangjun Liao","doi":"10.1016/j.medj.2024.07.006","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.006","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). To identify the determinants of response, we developed a TMEscore model to assess tumor microenvironment (TME), which was previously proven to be a biomarker for ICBs.</p><p><strong>Methods: </strong>A reference database of TMEscore assays was established using PCR assay kits containing 30 TME genes. This multi-center prospective clinical trial (NCT#04850716) included patients with mGC who were administered ICB combined with chemotherapy as a first-line regimen. Eighty-six tumor samples extracted from five medical centers before treatment were used to estimate the TMEscore, PD-L1 (CPS), and mismatch repair deficiency.</p><p><strong>Findings: </strong>The objective response rate (ORR) and median PFS of the cohort were 31.4% and six months. Enhanced ORR was observed in TMEscore-high mGC patients (ORR = 59%). The survival analysis demonstrated that high TMEscore was significantly associated with a more favorable PFS and OS. Moreover, TMEscore was found to be a predictive biomarker that surpassed MSI and CPS (AUC = 0.873, 0.511, and 0.524, respectively). By integrating the TMEscore and clinical variables, the fused model further enhances the predictive efficiency and translational application in a clinical setting.</p><p><strong>Conclusions: </strong>This prospective clinical study indicates that the TMEscore assay is a robust biomarker for screening patients with mGC who may derive survival benefits from ICB plus chemotherapy.</p><p><strong>Funding: </strong>Guangdong Basic and Applied Basic Research Foundation (2023A1515011214), Science and Technology Program of Guangzhou (202206080011), and Guangzhou Science and Technology Project (2023A03J0722 and 2023A04J2357).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876229","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":"Swept up in the tsunami: Pediatric and adolescent steatotic (fatty) liver disease.","authors":"Scott L Friedman","doi":"10.1016/j.medj.2024.04.007","DOIUrl":"https://doi.org/10.1016/j.medj.2024.04.007","url":null,"abstract":"<p><p>The worldwide epidemic of steatotic (fatty) liver disease also affects children and adolescents. The consensus statement by Zhang et al.¹ summarizes key evidence on detection, risk factors, manifestations, comorbidities, and potential treatments in children and adolescents. The work emphasizes the need for advancements in managing this threat to the health and longevity of young individuals.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604258","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":"Endoscopic duodenal mucosa ablation techniques for diabetes and nonalcoholic fatty liver disease: A systematic review.","authors":"Giovanni Musso, Silvia Pinach, Francesca Saba, Franco De Michieli, Maurizio Cassader, Roberto Gambino","doi":"10.1016/j.medj.2024.03.014","DOIUrl":"10.1016/j.medj.2024.03.014","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD).</p><p><strong>Methods: </strong>We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively.</p><p><strong>Findings: </strong>We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged.</p><p><strong>Conclusions: </strong>All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment.</p><p><strong>Funding: </strong>This study received no funding.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868222","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":"Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial.","authors":"Ehab Bakbak, Aishwarya Krishnaraj, Deepak L Bhatt, Adrian Quan, Brady Park, Asaad I Bakbak, Basel Bari, Kristin A Terenzi, Yi Pan, Elizabeth J Fry, Daniella C Terenzi, Pankaj Puar, Tayyab S Khan, Ori D Rotstein, C David Mazer, Lawrence A Leiter, Hwee Teoh, David A Hess, Subodh Verma","doi":"10.1016/j.medj.2024.03.009","DOIUrl":"10.1016/j.medj.2024.03.009","url":null,"abstract":"<p><strong>Background: </strong>REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) showed that icosapent ethyl (IPE) reduced major adverse cardiovascular events by 25%. Since the underlying mechanisms for these benefits are not fully understood, the IPE-PREVENTION CardioLink-14 trial (ClinicalTrials.gov: NCT04562467) sought to determine if IPE regulates vascular regenerative (VR) cell content in people with mild to moderate hypertriglyceridemia.</p><p><strong>Methods: </strong>Seventy statin-treated individuals with triglycerides ≥1.50 and <5.6 mmol/L and either atherosclerotic cardiovascular disease or type 2 diabetes with additional cardiovascular risk factors were randomized to IPE (4 g/day) or usual care. VR cells with high aldehyde dehydrogenase activity (ALDH^hi) were isolated from blood collected at the baseline and 3-month visits and characterized with lineage-specific cell surface markers. The primary endpoint was the change in frequency of pro-vascular ALDH^hiside scatter (SSC)^lowCD133⁺ progenitor cells. Change in frequencies of ALDH^hiSSC^mid monocyte and ALDH^hiSSC^hi granulocyte precursor subsets, reactive oxygen species production, serum biomarkers, and omega-3 levels were also evaluated.</p><p><strong>Findings: </strong>Baseline characteristics, cardiovascular risk factors, and medications were balanced between the groups. Compared to usual care, IPE increased the mean frequency of ALDH^hiSSC^lowCD133⁺ cells (-1.00% ± 2.45% vs. +7.79% ± 1.70%; p = 0.02), despite decreasing overall ALDH^hiSSC^low cell frequency. IPE assignment also reduced oxidative stress in ALDH^hiSSC^low progenitors and increased ALDH^hiSSC^hi granulocyte precursor cell content.</p><p><strong>Conclusions: </strong>IPE-PREVENTION CardioLink-14 provides the first translational evidence that IPE can modulate VR cell content and suggests a novel mechanism that may underlie the cardioprotective effects observed with IPE in REDUCE-IT.</p><p><strong>Funding: </strong>HLS Therapeutics provided the IPE in kind and had no role in the study design, conduct, analyses, or interpretation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327214","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":"An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.","authors":"Le Zhang, Mortada El-Shabrawi, Louise A Baur, Christopher D Byrne, Giovanni Targher, Mohit Kehar, Gilda Porta, Way Seah Lee, Sander Lefere, Serap Turan, Anna Alisi, Ram Weiss, Maria Felicia Faienza, Ambika Ashraf, Shikha S Sundaram, Anshu Srivastava, Ruth De Bruyne, Yunkoo Kang, Flora Bacopoulou, Yong-Hai Zhou, Andy Darma, Monica Lupsor-Platon, Masahide Hamaguchi, Anoop Misra, Nahum Méndez-Sánchez, Nicholas Beng Hui Ng, Claude Marcus, Amanda E Staiano, Nadia Waheed, Saleh A Alqahtani, Cosimo Giannini, Ponsiano Ocama, Mindie H Nguyen, Maria Teresa Arias-Loste, Mohamed Rabea Ahmed, Giada Sebastiani, Yong Poovorawan, Mamun Al Mahtab, Juan M Pericàs, Themis Reverbel da Silveira, Peter Hegyi, Amer Azaz, Hasan M Isa, Chatmanee Lertudomphonwanit, Mona Issa Farrag, Ahmed Abd Alwahab Nugud, Hong-Wei Du, Ke-Min Qi, Nezha Mouane, Xin-Ran Cheng, Tawfiq Al Lawati, Eleonora D T Fagundes, Hasmik Ghazinyan, Adamos Hadjipanayis, Jian-Gao Fan, Nicoleta Gimiga, Naglaa M Kamal, Gabriela Ștefănescu, Li Hong, Smaranda Diaconescu, Ming Li, Jacob George, Ming-Hua Zheng","doi":"10.1016/j.medj.2024.03.017","DOIUrl":"10.1016/j.medj.2024.03.017","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts.</p><p><strong>Methods: </strong>A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management.</p><p><strong>Findings: </strong>In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD.</p><p><strong>Conclusions: </strong>The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD.</p><p><strong>Funding: </strong>This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874811","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":"ALINA: Another stepping stone toward a future of LDCT lung cancer screening in never-smokers?","authors":"Misako Nagasaka, Catherine T Ly, Sai-Hong Ignatius Ou","doi":"10.1016/j.medj.2024.05.010","DOIUrl":"https://doi.org/10.1016/j.medj.2024.05.010","url":null,"abstract":"<p><p>The ALINA trial¹ demonstrated that 2 years of adjuvant alectinib achieved statistically significantly improved 2-year overall and central nervous system (CNS) disease-free survival over platinum-doublet chemotherapy in resected early-stage (IB ≥ 4 cm to IIIA) ALK+ non-small cell lung cancer (NSCLC). Identifying early-stage ALK+ NSCLC patients (60% were never-smokers in the ALINA trial) may require low-dose computed tomography (LDCT) lung cancer screening in never-smokers.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604256","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":"Normal or improved cardiovascular risk factors in IGF-I-deficient adults with growth hormone receptor deficiency.","authors":"Jaime Guevara-Aguirre, Amrendra Mishra, Marco Canepa, Carolina Guevara, Álvaro Villacres, Alexandra Guevara, Gabriela Peña, Daniela Lescano, John J Kopchick, Priya Balasubramanian, Valter D Longo","doi":"10.1016/j.medj.2024.03.022","DOIUrl":"10.1016/j.medj.2024.03.022","url":null,"abstract":"<p><strong>Background: </strong>Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives.</p><p><strong>Methods: </strong>We measured markers of CVD in two phases: one in a cohort of 30 individuals (GHRD = 16, control relatives = 14) brought to USC (in Los Angeles, CA) and one in a cohort including additional individuals examined in Ecuador (where the subjects live) for a total of 44 individuals (GHRD = 21, control relatives = 23). Data were collected on GHRD and control groups living in similar geographical locations and sharing comparable environmental and socio-economic circumstances.</p><p><strong>Results: </strong>Compared to controls, GHRD subjects displayed lower serum glucose, insulin, blood pressure, smaller cardiac dimensions, similar pulse wave velocity, lower carotid artery intima-media thickness, lower creatinine, and a non-significant but major reduction in the portion of subjects with carotid atherosclerotic plaques (7% GHRDs vs. 36%, Controls p = 0.1333) despite elevated low-density lipoprotein cholesterol levels.</p><p><strong>Conclusion: </strong>The current study indicates that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors as compared to their relatives.</p><p><strong>Funding: </strong>This study was funded in part by NIH/NIA grant P01 AG034906 to V.D.L.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865271","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}