Pub Date : 2024-10-30DOI: 10.1038/s43856-024-00652-2
David Cheishvili, Chifat Wong, Mohammad Mahbubul Karim, Mohammad Golam Kibria, Nusrat Jahan, Pappu Chandra Das, Abul Khair Yousuf, Atikul Islam, Dulal Chandra Das, Sheikh Mohammad Noor-E-Alam, Sarwar Alam, Mustafizur Rahman, Wasif A. Khan, Mamun Al-Mahtab, Moshe Szyf
Hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally, poses significant challenges in early detection. Improved diagnostic accuracy can drastically influence patient outcomes, emphasizing the need for innovative, non-invasive biomarkers. This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP). Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2–95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone. Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients. Cheishvili et al. investigate the use of DNA methylation markers in peripheral blood mononuclear cells for early detection of hepatocellular carcinoma in an Asian cohort. The study demonstrates that these biomarkers can accurately distinguish between healthy controls and patients across different stages of the disease. Liver cancer is one of the top causes of cancer death worldwide, and finding it early is crucial for successful treatment. This research focuses on using a simple blood test to look for specific DNA changes that signal the early stages of liver cancer. We tested this method on a diverse group of people from Bangladesh, including those already at high risk for liver cancer due to chronic liver infections. By combining this new blood test with other existing tests, we were able to detect liver cancer more accurately and earlier than by using traditional methods alone. This approach could make it easier and less invasive to find liver cancer early, offering a better chance for effective treatment and a hopeful prognosis for those at risk.
{"title":"Clinical validation of peripheral blood mononuclear cell DNA methylation markers for accurate early detection of hepatocellular carcinoma in Asian patients","authors":"David Cheishvili, Chifat Wong, Mohammad Mahbubul Karim, Mohammad Golam Kibria, Nusrat Jahan, Pappu Chandra Das, Abul Khair Yousuf, Atikul Islam, Dulal Chandra Das, Sheikh Mohammad Noor-E-Alam, Sarwar Alam, Mustafizur Rahman, Wasif A. Khan, Mamun Al-Mahtab, Moshe Szyf","doi":"10.1038/s43856-024-00652-2","DOIUrl":"10.1038/s43856-024-00652-2","url":null,"abstract":"Hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally, poses significant challenges in early detection. Improved diagnostic accuracy can drastically influence patient outcomes, emphasizing the need for innovative, non-invasive biomarkers. This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP). Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2–95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone. Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients. Cheishvili et al. investigate the use of DNA methylation markers in peripheral blood mononuclear cells for early detection of hepatocellular carcinoma in an Asian cohort. The study demonstrates that these biomarkers can accurately distinguish between healthy controls and patients across different stages of the disease. Liver cancer is one of the top causes of cancer death worldwide, and finding it early is crucial for successful treatment. This research focuses on using a simple blood test to look for specific DNA changes that signal the early stages of liver cancer. We tested this method on a diverse group of people from Bangladesh, including those already at high risk for liver cancer due to chronic liver infections. By combining this new blood test with other existing tests, we were able to detect liver cancer more accurately and earlier than by using traditional methods alone. This approach could make it easier and less invasive to find liver cancer early, offering a better chance for effective treatment and a hopeful prognosis for those at risk.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-14"},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549285","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}
Pub Date : 2024-10-29DOI: 10.1038/s43856-024-00649-x
Luis Antonio Díaz, Jeffrey V. Lazarus, Eduardo Fuentes-López, Francisco Idalsoaga, Gustavo Ayares, Hailemichael Desaleng, Pojsakorn Danpanichkul, Thomas G. Cotter, Winston Dunn, Francisco Barrera, Karn Wijarnpreecha, Mazen Noureddin, Naim Alkhouri, Ashwani K. Singal, Robert J. Wong, Zobair M. Younossi, Mary E. Rinella, Patrick S. Kamath, Ramon Bataller, Rohit Loomba, Marco Arrese, Juan Pablo Arab
The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. We undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated. This study aims to estimate the prevalence of different types of fatty liver disease, in which excess fat occurs in the liver. A particular type of fatty liver disease that is not caused by excess alcohol consumption affects 42.4% of adults in the USA, with men, older adults, and Hispanics being more likely to have this form of liver disease. People with health insurance are less likely to have liver disease caused by excess alcohol consumption. These results highlight the importance of targeted prevention efforts in people with a higher risk of developing liver disease. Future public health strategies should focus on reducing risk factors and providing equitable healthcare access. Díaz et al. estimate the prevalence of steatotic liver disease (SLD) in adults in the United States. Increased waist circumference, excess weight, abnormal glucose metabolism, and hypertension are associated with a higher risk of advanced fibrosis in SLD, with sex, hispanic ethnicity and lack of health insurance associated with certain types.
{"title":"Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria","authors":"Luis Antonio Díaz, Jeffrey V. Lazarus, Eduardo Fuentes-López, Francisco Idalsoaga, Gustavo Ayares, Hailemichael Desaleng, Pojsakorn Danpanichkul, Thomas G. Cotter, Winston Dunn, Francisco Barrera, Karn Wijarnpreecha, Mazen Noureddin, Naim Alkhouri, Ashwani K. Singal, Robert J. Wong, Zobair M. Younossi, Mary E. Rinella, Patrick S. Kamath, Ramon Bataller, Rohit Loomba, Marco Arrese, Juan Pablo Arab","doi":"10.1038/s43856-024-00649-x","DOIUrl":"10.1038/s43856-024-00649-x","url":null,"abstract":"The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. We undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated. This study aims to estimate the prevalence of different types of fatty liver disease, in which excess fat occurs in the liver. A particular type of fatty liver disease that is not caused by excess alcohol consumption affects 42.4% of adults in the USA, with men, older adults, and Hispanics being more likely to have this form of liver disease. People with health insurance are less likely to have liver disease caused by excess alcohol consumption. These results highlight the importance of targeted prevention efforts in people with a higher risk of developing liver disease. Future public health strategies should focus on reducing risk factors and providing equitable healthcare access. Díaz et al. estimate the prevalence of steatotic liver disease (SLD) in adults in the United States. Increased waist circumference, excess weight, abnormal glucose metabolism, and hypertension are associated with a higher risk of advanced fibrosis in SLD, with sex, hispanic ethnicity and lack of health insurance associated with certain types.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-11"},"PeriodicalIF":5.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549286","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}
Pub Date : 2024-10-29DOI: 10.1038/s43856-024-00653-1
Ram Kinker Mishra, Adonay S. Nunes, Ana Enriquez, Victoria R. Profeta, McKenzie Wells, David R. Lynch, Ashkan Vaziri
Friedreich ataxia (FRDA) results in progressive impairment in gait, upper extremity coordination, and speech. Currently, these symptoms are assessed through expert examination at clinical visits. Such in-clinic assessments are time-consuming, subjective, of limited sensitivity, and provide only a limited perspective of the daily disability of patients. In this study, we recruited 39 FRDA patients and remotely monitored their physical activity and upper extremity function using a set of wearable sensors for 7 consecutive days. We compared the sensor-derived metrics of lower and upper extremity function as measured during activities of daily living with FRDA clinical measures (e.g., mFARS and FA-ADL) and biological biomarkers of disease severity (guanine-adenine-adenine (GAA) and frataxin (FXN) levels), using Spearman correlation analyses. The results show significant correlations with moderate to high effect sizes between multiple sensor-derived metrics and the FRDA clinical and biological outcomes. In addition, we develop multiple machine learning-based models to predict disease severity in FRDA using demographic, biological, and sensor-derived metrics. When sensor-derived metrics are included, the model performance enhances 1.5-fold and 2-fold in terms of explained variance, R², for predicting FRDA clinical measures and biological biomarkers of disease severity, respectively. Our results establish the initial clinical validity of using wearable sensors in assessing disease severity and monitoring motor dysfunction in FRDA. Friedreich ataxia (FRDA) is a condition that impairs movement and coordination. Current clinical assessments are subjective, highlighting the need for better ways to monitor disease severity. By using wearable devices to track symptoms in everyday life, we can gain better insights into how patients function outside the clinical environment, offering a more comprehensive understanding of the disease’s impact. In this study, 39 patients were observed using wearable sensors for a week to track their physical activity and arm movements. The data collected was compared with traditional clinical tests and biological markers of the disease. The findings demonstrate that wearable sensors can accurately predict disease severity, offering continuous real-world monitoring that could enhance patient care and treatment outcomes. Mishra, Nunes et al. monitor the physical activity and upper limb function of 39 people with Friedreich ataxia (FRDA) using wearable sensors over 7 days. The results demonstrate that incorporating sensor data significantly enhances predictive models of disease severity, offering a comprehensive approach to assessing and monitoring FRDA.
{"title":"At-home wearable-based monitoring predicts clinical measures and biological biomarkers of disease severity in Friedreich’s Ataxia","authors":"Ram Kinker Mishra, Adonay S. Nunes, Ana Enriquez, Victoria R. Profeta, McKenzie Wells, David R. Lynch, Ashkan Vaziri","doi":"10.1038/s43856-024-00653-1","DOIUrl":"10.1038/s43856-024-00653-1","url":null,"abstract":"Friedreich ataxia (FRDA) results in progressive impairment in gait, upper extremity coordination, and speech. Currently, these symptoms are assessed through expert examination at clinical visits. Such in-clinic assessments are time-consuming, subjective, of limited sensitivity, and provide only a limited perspective of the daily disability of patients. In this study, we recruited 39 FRDA patients and remotely monitored their physical activity and upper extremity function using a set of wearable sensors for 7 consecutive days. We compared the sensor-derived metrics of lower and upper extremity function as measured during activities of daily living with FRDA clinical measures (e.g., mFARS and FA-ADL) and biological biomarkers of disease severity (guanine-adenine-adenine (GAA) and frataxin (FXN) levels), using Spearman correlation analyses. The results show significant correlations with moderate to high effect sizes between multiple sensor-derived metrics and the FRDA clinical and biological outcomes. In addition, we develop multiple machine learning-based models to predict disease severity in FRDA using demographic, biological, and sensor-derived metrics. When sensor-derived metrics are included, the model performance enhances 1.5-fold and 2-fold in terms of explained variance, R², for predicting FRDA clinical measures and biological biomarkers of disease severity, respectively. Our results establish the initial clinical validity of using wearable sensors in assessing disease severity and monitoring motor dysfunction in FRDA. Friedreich ataxia (FRDA) is a condition that impairs movement and coordination. Current clinical assessments are subjective, highlighting the need for better ways to monitor disease severity. By using wearable devices to track symptoms in everyday life, we can gain better insights into how patients function outside the clinical environment, offering a more comprehensive understanding of the disease’s impact. In this study, 39 patients were observed using wearable sensors for a week to track their physical activity and arm movements. The data collected was compared with traditional clinical tests and biological markers of the disease. The findings demonstrate that wearable sensors can accurately predict disease severity, offering continuous real-world monitoring that could enhance patient care and treatment outcomes. Mishra, Nunes et al. monitor the physical activity and upper limb function of 39 people with Friedreich ataxia (FRDA) using wearable sensors over 7 days. The results demonstrate that incorporating sensor data significantly enhances predictive models of disease severity, offering a comprehensive approach to assessing and monitoring FRDA.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-9"},"PeriodicalIF":5.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523761","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}
Pub Date : 2024-10-29DOI: 10.1038/s43856-024-00618-4
Arun R. Sridhar, Jim W. Cheung, Rachel Lampert, Jennifer N. A. Silva, Rakesh Gopinathannair, Juan C. Sotomonte, Khaldoun Tarakji, Mark Fellman, Jonathan Chrispin, Niraj Varma, Rajesh Kabra, Nishaki Mehta, Sana M Al-Khatib, Jacob J. Mayfield, Rachita Navara, Bharath Rajagopalan, Rod Passman, Yann Fleureau, Maully J Shah, Mintu Turakhia, Dhanunjaya Lakkireddy
The rapid growth in consumer-facing mobile and sensor technologies has created tremendous opportunities for patient-driven personalized health management. The diagnosis and management of cardiac arrhythmias are particularly well suited to benefit from these easily accessible consumer health technologies. In particular, smartphone-based and wrist-worn wearable electrocardiogram (ECG) and photoplethysmography (PPG) technology can facilitate relatively inexpensive, long-term rhythm monitoring. Here we review the practical utility of the currently available and emerging mobile health technologies relevant to cardiac arrhythmia care. We discuss the applications of these tools, which vary with respect to diagnostic performance, target populations, and indications. We also highlight that requirements for successful integration into clinical practice require adaptations to regulatory approval, data management, electronic medical record integration, quality oversight, and efforts to minimize the additional burden to health care professionals. Sridhar et al. review the opportunities that mobile health technologies offer to improve the care of patients with cardiac arrhythmias. The current status, challenges, and future opportunities to use these technologies to predict, screen, diagnose, and manage of cardiac arrhythmias are highlighted.
{"title":"State of the art of mobile health technologies use in clinical arrhythmia care","authors":"Arun R. Sridhar, Jim W. Cheung, Rachel Lampert, Jennifer N. A. Silva, Rakesh Gopinathannair, Juan C. Sotomonte, Khaldoun Tarakji, Mark Fellman, Jonathan Chrispin, Niraj Varma, Rajesh Kabra, Nishaki Mehta, Sana M Al-Khatib, Jacob J. Mayfield, Rachita Navara, Bharath Rajagopalan, Rod Passman, Yann Fleureau, Maully J Shah, Mintu Turakhia, Dhanunjaya Lakkireddy","doi":"10.1038/s43856-024-00618-4","DOIUrl":"10.1038/s43856-024-00618-4","url":null,"abstract":"The rapid growth in consumer-facing mobile and sensor technologies has created tremendous opportunities for patient-driven personalized health management. The diagnosis and management of cardiac arrhythmias are particularly well suited to benefit from these easily accessible consumer health technologies. In particular, smartphone-based and wrist-worn wearable electrocardiogram (ECG) and photoplethysmography (PPG) technology can facilitate relatively inexpensive, long-term rhythm monitoring. Here we review the practical utility of the currently available and emerging mobile health technologies relevant to cardiac arrhythmia care. We discuss the applications of these tools, which vary with respect to diagnostic performance, target populations, and indications. We also highlight that requirements for successful integration into clinical practice require adaptations to regulatory approval, data management, electronic medical record integration, quality oversight, and efforts to minimize the additional burden to health care professionals. Sridhar et al. review the opportunities that mobile health technologies offer to improve the care of patients with cardiac arrhythmias. The current status, challenges, and future opportunities to use these technologies to predict, screen, diagnose, and manage of cardiac arrhythmias are highlighted.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-14"},"PeriodicalIF":5.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549300","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}
Pub Date : 2024-10-25DOI: 10.1038/s43856-024-00648-y
Maximiliano Presa, Vi Pham, Somdatta Ray, Pierre-Alexandre Piec, Jennifer Ryan, Timothy Billings, Harold Coombs, Lars Schlotawa, Troy Lund, Rebecca C. Ahrens-Nicklas, Cathleen Lutz
Multiple Sulfatase Deficiency (MSD) is an ultra-rare autosomal recessive disorder characterized by deficient enzymatic activity of all known sulfatases. MSD patients frequently carry two loss of function mutations in the SUMF1 gene, encoding a formylglycine-generating enzyme (FGE) that activates 17 different sulfatases. MSD patients show common features of other lysosomal diseases like mucopolysaccharidosis and metachromatic leukodystrophy, including neurologic impairments, developmental delay, and visceromegaly. There are currently no approved therapies for MSD patients. Hematopoietic stem cell transplant (HSCT) has been applied with success in the treatment of certain lysosomal diseases. In HSCT, donor-derived myeloid cells are a continuous source of active sulfatase enzymes that can be taken up by sulfatase-deficient host cells. Thus, HSCT could be a potential approach for the treatment of MSD. To test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1(S153P/S153P) mice, engrafted with bone marrow cells, Sumf1+/+, from B6-PtprcK302E mice (CD45.1 immunoreactive). After 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1(+/+)). Enzymatic activity for ARSA, ARSB, and SGSH is significantly increased in spleen of B6-Sumf1(S153P/S153P) recipient mice. In non-lymphoid organs, only liver and heart show a significant correction of sulfatase activity and GAG accumulation. Frequency of inflammatory cells and lysosomal pathology is significantly reduced in liver and heart, while no significant improvement is detected in brain. Our results indicate that HSCT could be a suitable approach to treat MSD-pathology affecting peripheral organs, however that benefit to CNS pathology might be limited. Multiple Sulfatase Deficiency (MSD) is a rare genetic disorder caused by loss-of-function variations in the SUMF1 gene. This deficiency results in the accumulation of toxic compounds, leading to developmental delays and neurological impairments. In a bone marrow transplant (BMT), donor cells are infused into the patient and secrete active proteins that can help remove those toxic compounds. We carried out BMT in a mouse model for MSD and saw beneficial effects on peripheral organs, such as the liver and heart, but less change in neurological symptoms. Our results will be useful for the design of potential cell therapy approaches that could be used clinically to treat MSD. Presa et al. use a mouse model of multiple sulfatase deficiency (MSD) to assess efficacy of bone marrow transplantation to increase sulfatase activity. Sulfatase activity is partially restored in some peripheral tissues such as spleen, liver and heart, but no significant benefit is observed in the brain.
{"title":"Bone marrow transplantation increases sulfatase activity in somatic tissues in a multiple sulfatase deficiency mouse model","authors":"Maximiliano Presa, Vi Pham, Somdatta Ray, Pierre-Alexandre Piec, Jennifer Ryan, Timothy Billings, Harold Coombs, Lars Schlotawa, Troy Lund, Rebecca C. Ahrens-Nicklas, Cathleen Lutz","doi":"10.1038/s43856-024-00648-y","DOIUrl":"10.1038/s43856-024-00648-y","url":null,"abstract":"Multiple Sulfatase Deficiency (MSD) is an ultra-rare autosomal recessive disorder characterized by deficient enzymatic activity of all known sulfatases. MSD patients frequently carry two loss of function mutations in the SUMF1 gene, encoding a formylglycine-generating enzyme (FGE) that activates 17 different sulfatases. MSD patients show common features of other lysosomal diseases like mucopolysaccharidosis and metachromatic leukodystrophy, including neurologic impairments, developmental delay, and visceromegaly. There are currently no approved therapies for MSD patients. Hematopoietic stem cell transplant (HSCT) has been applied with success in the treatment of certain lysosomal diseases. In HSCT, donor-derived myeloid cells are a continuous source of active sulfatase enzymes that can be taken up by sulfatase-deficient host cells. Thus, HSCT could be a potential approach for the treatment of MSD. To test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1(S153P/S153P) mice, engrafted with bone marrow cells, Sumf1+/+, from B6-PtprcK302E mice (CD45.1 immunoreactive). After 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1(+/+)). Enzymatic activity for ARSA, ARSB, and SGSH is significantly increased in spleen of B6-Sumf1(S153P/S153P) recipient mice. In non-lymphoid organs, only liver and heart show a significant correction of sulfatase activity and GAG accumulation. Frequency of inflammatory cells and lysosomal pathology is significantly reduced in liver and heart, while no significant improvement is detected in brain. Our results indicate that HSCT could be a suitable approach to treat MSD-pathology affecting peripheral organs, however that benefit to CNS pathology might be limited. Multiple Sulfatase Deficiency (MSD) is a rare genetic disorder caused by loss-of-function variations in the SUMF1 gene. This deficiency results in the accumulation of toxic compounds, leading to developmental delays and neurological impairments. In a bone marrow transplant (BMT), donor cells are infused into the patient and secrete active proteins that can help remove those toxic compounds. We carried out BMT in a mouse model for MSD and saw beneficial effects on peripheral organs, such as the liver and heart, but less change in neurological symptoms. Our results will be useful for the design of potential cell therapy approaches that could be used clinically to treat MSD. Presa et al. use a mouse model of multiple sulfatase deficiency (MSD) to assess efficacy of bone marrow transplantation to increase sulfatase activity. Sulfatase activity is partially restored in some peripheral tissues such as spleen, liver and heart, but no significant benefit is observed in the brain.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-12"},"PeriodicalIF":5.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514027","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}
Pub Date : 2024-10-25DOI: 10.1038/s43856-024-00639-z
Allan Kalungi, Dan J. Stein, Niran Okewole, Segun Fatumo
African populations are currently underrepresented in global psychiatric genetics research. Here, we highlight the importance of conducting psychiatric genetics research in Africa, key issues which have hindered such research, and ongoing initiatives and strategies to overcome these issues. Kalungi et al. highlight the underrepresentation of African populations in psychiatric genetic research. They advocate for strategic investments, capacity building, and collaboration to empower African scientists and institutions, emphasizing community engagement and ethical considerations for robust and culturally sensitive research in Africa.
{"title":"Approaches to enable equitable psychiatric genetic research in Africa","authors":"Allan Kalungi, Dan J. Stein, Niran Okewole, Segun Fatumo","doi":"10.1038/s43856-024-00639-z","DOIUrl":"10.1038/s43856-024-00639-z","url":null,"abstract":"African populations are currently underrepresented in global psychiatric genetics research. Here, we highlight the importance of conducting psychiatric genetics research in Africa, key issues which have hindered such research, and ongoing initiatives and strategies to overcome these issues. Kalungi et al. highlight the underrepresentation of African populations in psychiatric genetic research. They advocate for strategic investments, capacity building, and collaboration to empower African scientists and institutions, emphasizing community engagement and ethical considerations for robust and culturally sensitive research in Africa.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-4"},"PeriodicalIF":5.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514026","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}
Pub Date : 2024-10-24DOI: 10.1038/s43856-024-00636-2
George Clarke, Jingwen Mao, Angus Hann, Yiyu Fan, Amita Gupta, Anisa Nutu, Erwin Buckel Schaffner, Kayani Kayani, Nicholas Murphy, Mansoor N. Bangash, Anna L. Casey, Isla Wootton, Alexander J. Lawson, Bobby V. M. Dasari, M. Thamara P. R. Perera, Hynek Mergental, Simon C. Afford
Normothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements. We set out to develop a reproducible protocol for the extended normothermic machine perfusion of whole human livers. Human livers declined for transplantation were perfused using a blood-based perfusate at 36 °C using the Liver Assist device (XVIVO, Sweden), with continuous veno-venous haemofiltration in-parallel. We developed the protocol in a stepwise fashion. Perfusion techniques utilised included: targeted physiological vascular flows, phosphate replacement (to prevent hypophosphataemia), N-acetylcysteine (to prevent methaemoglobin accumulation), and the utilisation of sodium lactate as both a nutritional source and real-time measure of hepatocyte function. All five human livers perfused with the developed protocol showed preserved function with a median perfusion time of 168 h (range 120–184 h), with preserved viability throughout. Livers can be reproducibly perfused in excess of 120 (range 121–184) hours with evidence of preserved hepatocyte and cholangiocyte function. Clarke et al. present a reproducible protocol for the extended normothermic machine perfusion of human livers. Function and are preserved in five human livers perfused between 121–184 h. Circulating blood through human livers at normal body temperature allows transplant surgeons to assess the function of the liver and safely extend the time it is out of the body prior to transplantation. Extending this perfusion of livers beyond 24 h has proven difficult. We evaluated improved techniques to circulate blood through the liver. We found the improved techniques could enable a machine to be used to reliably perfuse livers for more than 24 h, whilst preserving the function of the liver. Our improved method included varying the blood flow according to liver size and removing waste products from the circulating blood. Using our method could enable more livers to be used successfully in transplant operations, reducing the waiting times for people requiring liver transplantation and improving their quality of life.
{"title":"A reproducible extended ex-vivo normothermic machine liver perfusion protocol utilising improved nutrition and targeted vascular flows","authors":"George Clarke, Jingwen Mao, Angus Hann, Yiyu Fan, Amita Gupta, Anisa Nutu, Erwin Buckel Schaffner, Kayani Kayani, Nicholas Murphy, Mansoor N. Bangash, Anna L. Casey, Isla Wootton, Alexander J. Lawson, Bobby V. M. Dasari, M. Thamara P. R. Perera, Hynek Mergental, Simon C. Afford","doi":"10.1038/s43856-024-00636-2","DOIUrl":"10.1038/s43856-024-00636-2","url":null,"abstract":"Normothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements. We set out to develop a reproducible protocol for the extended normothermic machine perfusion of whole human livers. Human livers declined for transplantation were perfused using a blood-based perfusate at 36 °C using the Liver Assist device (XVIVO, Sweden), with continuous veno-venous haemofiltration in-parallel. We developed the protocol in a stepwise fashion. Perfusion techniques utilised included: targeted physiological vascular flows, phosphate replacement (to prevent hypophosphataemia), N-acetylcysteine (to prevent methaemoglobin accumulation), and the utilisation of sodium lactate as both a nutritional source and real-time measure of hepatocyte function. All five human livers perfused with the developed protocol showed preserved function with a median perfusion time of 168 h (range 120–184 h), with preserved viability throughout. Livers can be reproducibly perfused in excess of 120 (range 121–184) hours with evidence of preserved hepatocyte and cholangiocyte function. Clarke et al. present a reproducible protocol for the extended normothermic machine perfusion of human livers. Function and are preserved in five human livers perfused between 121–184 h. Circulating blood through human livers at normal body temperature allows transplant surgeons to assess the function of the liver and safely extend the time it is out of the body prior to transplantation. Extending this perfusion of livers beyond 24 h has proven difficult. We evaluated improved techniques to circulate blood through the liver. We found the improved techniques could enable a machine to be used to reliably perfuse livers for more than 24 h, whilst preserving the function of the liver. Our improved method included varying the blood flow according to liver size and removing waste products from the circulating blood. Using our method could enable more livers to be used successfully in transplant operations, reducing the waiting times for people requiring liver transplantation and improving their quality of life.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-12"},"PeriodicalIF":5.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516777","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}
Pub Date : 2024-10-24DOI: 10.1038/s43856-024-00628-2
Shihui Jin, Alex R. Cook, Robert Kanwagi, Heidi J. Larson, Leesa Lin
In the midst of the global COVID-19 vaccine distribution challenge, religion stands out as a key determinant of vaccine hesitancy and health choices. Notably, the multifaceted religious environments of Africa and the Asia Pacific remain under-researched in this context. Utilizing data from two survey waves conducted between 2021 and 2022, this cross-sectional study investigated the effects of religious beliefs on perceptions of compatibility between religion and vaccines and COVID-19 vaccine acceptance in Africa and Asia Pacific. Logistic regression models were employed, with interaction terms between socio-economic factors incorporated to account for variations among diverse subpopulations. Among the eight religious groups identified, Atheists and Buddhists in the Asia Pacific exhibit the lowest agreement, with fewer than 60% acknowledging the religious compatibility of vaccines. Willingness to accept vaccines, however, is consistently higher in Asia Pacific by at least four percentage points compared to Africa, with the disparity widening further in the second wave. Impacts of education on vaccine perceptions vary across religious groups, while acknowledging vaccine compatibility with religion positively contributed to vaccine acceptance. Dynamics between region, religion, and other socio-demographic factors have changed substantially over time. All but Atheists and Muslims exhibit a higher propensity to endorse vaccines during Survey Wave 2. Our study reveals complex, context-dependent connections between vaccine attitudes and religion and the heterogeneous effects of time and education among different religious affiliations. Understanding the underlying drivers of these temporal variations helps inform tailored approaches aimed at addressing vaccine hesitancy, promoting vaccine uptake, and improving the well-being of each religious group. This study examined the effects of religious beliefs on thoughts about agreement between religion and vaccines, and COVID-19 vaccine acceptance in Africa and Asia Pacific. Data came from surveys of individuals across many regions during the COVID-19 pandemic in 2021 and 2022. We found lower agreement to compatibility between vaccine and religious belief among Atheists and Buddhists in the Asia Pacific, while Africans were generally less likely to accept the COVID-19 vaccines. In addition, education influenced vaccine views differently across religious groups, and those who felt vaccination was compatible with their religion were more likely to accept a vaccine. These findings show we should monitor vaccine confidence and tailor efforts to reduce vaccine hesitancy among different subgroups of people. Jin et al. explore the role of religion in perception of COVID-19 vaccination across Africa and Asia Pacific regions. They highlight important similarities and differences that may help inform future public health interventions around preventative medicine.
{"title":"Comparing role of religion in perception of the COVID-19 vaccines in Africa and Asia Pacific","authors":"Shihui Jin, Alex R. Cook, Robert Kanwagi, Heidi J. Larson, Leesa Lin","doi":"10.1038/s43856-024-00628-2","DOIUrl":"10.1038/s43856-024-00628-2","url":null,"abstract":"In the midst of the global COVID-19 vaccine distribution challenge, religion stands out as a key determinant of vaccine hesitancy and health choices. Notably, the multifaceted religious environments of Africa and the Asia Pacific remain under-researched in this context. Utilizing data from two survey waves conducted between 2021 and 2022, this cross-sectional study investigated the effects of religious beliefs on perceptions of compatibility between religion and vaccines and COVID-19 vaccine acceptance in Africa and Asia Pacific. Logistic regression models were employed, with interaction terms between socio-economic factors incorporated to account for variations among diverse subpopulations. Among the eight religious groups identified, Atheists and Buddhists in the Asia Pacific exhibit the lowest agreement, with fewer than 60% acknowledging the religious compatibility of vaccines. Willingness to accept vaccines, however, is consistently higher in Asia Pacific by at least four percentage points compared to Africa, with the disparity widening further in the second wave. Impacts of education on vaccine perceptions vary across religious groups, while acknowledging vaccine compatibility with religion positively contributed to vaccine acceptance. Dynamics between region, religion, and other socio-demographic factors have changed substantially over time. All but Atheists and Muslims exhibit a higher propensity to endorse vaccines during Survey Wave 2. Our study reveals complex, context-dependent connections between vaccine attitudes and religion and the heterogeneous effects of time and education among different religious affiliations. Understanding the underlying drivers of these temporal variations helps inform tailored approaches aimed at addressing vaccine hesitancy, promoting vaccine uptake, and improving the well-being of each religious group. This study examined the effects of religious beliefs on thoughts about agreement between religion and vaccines, and COVID-19 vaccine acceptance in Africa and Asia Pacific. Data came from surveys of individuals across many regions during the COVID-19 pandemic in 2021 and 2022. We found lower agreement to compatibility between vaccine and religious belief among Atheists and Buddhists in the Asia Pacific, while Africans were generally less likely to accept the COVID-19 vaccines. In addition, education influenced vaccine views differently across religious groups, and those who felt vaccination was compatible with their religion were more likely to accept a vaccine. These findings show we should monitor vaccine confidence and tailor efforts to reduce vaccine hesitancy among different subgroups of people. Jin et al. explore the role of religion in perception of COVID-19 vaccination across Africa and Asia Pacific regions. They highlight important similarities and differences that may help inform future public health interventions around preventative medicine.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-9"},"PeriodicalIF":5.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514028","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}
Pub Date : 2024-10-24DOI: 10.1038/s43856-024-00638-0
Lucie Bourguignon, Louis P. Lukas, Bethany R. Kondiles, Bobo Tong, Jaimie J. Lee, Tomás Gomes, Wolfram Tetzlaff, John L. K. Kramer, Matthias Walter, Catherine R. Jutzeler
Complications arising from acute traumatic spinal cord injury (SCI) are routinely managed by various pharmacological interventions. Despite decades of clinical application, the potential impact on neurological recovery has been largely overlooked. This study aims to highlight commonly administered drugs with potential disease-modifying effects. This systematic literature review included studies referenced in PubMed, Scopus and Web of Science from inception to March 31st, 2021, which assess disease-modifying properties on neurological and/or functional recovery of drugs routinely administered following spinal cord injury. Drug effects were classified as positive, negative, mixed, no effect, or not (statistically) reported. Risk of bias was assessed separately for animal, randomized clinical trials, and observational human studies. We analyzed 394 studies conducting 486 experiments that evaluated 144 unique or combinations of drugs. 195 of the 464 experiments conducted on animals (42%) and one study in humans demonstrate positive disease-modifying properties on neurological and/or functional outcomes. Methylprednisolone, melatonin, estradiol, and atorvastatin are the most common drugs associated with positive effects. Two studies on morphine and ethanol report negative effects on recovery. Despite a large heterogeneity observed in study protocols, research from bed to bench and back to bedside provides an alternative approach to identify new candidate drugs in the context of SCI. Future research in human populations is warranted to determine if introducing drugs like melatonin, estradiol, or atorvastatin would contribute to enhancing neurological outcomes after acute SCI. Patients with spinal cord injury (SCI) are exposed to a wide range of medications treating health conditions arising as a consequence of the initial injury. The effect of providing patients with a large number of medications in the early period after injury, that is in the first days to weeks, on recovery from SCI, however, is typically not considered. This extensive and structured review of evidence from pre-clinical (animal) and clinical (human) studies quantifies these effects for the first time. 144 unique drugs or combinations of drugs previously reported to be administered in animal models or to patients with SCI have been studied for their effect on recovery across 486 distinct experiments. A small subset of drugs are associated with positive effects, and provide potential targets for further study to determine if they can be used to treat SCI. Bourguignon, Lukas et al. systematically review the effect of drugs commonly administered after traumatic spinal cord injury on the neurological recovery in both animal studies and humans. Extensive heterogeneity in study characteristics and results highlight the need for harmonization across the field but also the potential for drug repurposing.
{"title":"Impact of commonly administered drugs on the progression of spinal cord injury: a systematic review","authors":"Lucie Bourguignon, Louis P. Lukas, Bethany R. Kondiles, Bobo Tong, Jaimie J. Lee, Tomás Gomes, Wolfram Tetzlaff, John L. K. Kramer, Matthias Walter, Catherine R. Jutzeler","doi":"10.1038/s43856-024-00638-0","DOIUrl":"10.1038/s43856-024-00638-0","url":null,"abstract":"Complications arising from acute traumatic spinal cord injury (SCI) are routinely managed by various pharmacological interventions. Despite decades of clinical application, the potential impact on neurological recovery has been largely overlooked. This study aims to highlight commonly administered drugs with potential disease-modifying effects. This systematic literature review included studies referenced in PubMed, Scopus and Web of Science from inception to March 31st, 2021, which assess disease-modifying properties on neurological and/or functional recovery of drugs routinely administered following spinal cord injury. Drug effects were classified as positive, negative, mixed, no effect, or not (statistically) reported. Risk of bias was assessed separately for animal, randomized clinical trials, and observational human studies. We analyzed 394 studies conducting 486 experiments that evaluated 144 unique or combinations of drugs. 195 of the 464 experiments conducted on animals (42%) and one study in humans demonstrate positive disease-modifying properties on neurological and/or functional outcomes. Methylprednisolone, melatonin, estradiol, and atorvastatin are the most common drugs associated with positive effects. Two studies on morphine and ethanol report negative effects on recovery. Despite a large heterogeneity observed in study protocols, research from bed to bench and back to bedside provides an alternative approach to identify new candidate drugs in the context of SCI. Future research in human populations is warranted to determine if introducing drugs like melatonin, estradiol, or atorvastatin would contribute to enhancing neurological outcomes after acute SCI. Patients with spinal cord injury (SCI) are exposed to a wide range of medications treating health conditions arising as a consequence of the initial injury. The effect of providing patients with a large number of medications in the early period after injury, that is in the first days to weeks, on recovery from SCI, however, is typically not considered. This extensive and structured review of evidence from pre-clinical (animal) and clinical (human) studies quantifies these effects for the first time. 144 unique drugs or combinations of drugs previously reported to be administered in animal models or to patients with SCI have been studied for their effect on recovery across 486 distinct experiments. A small subset of drugs are associated with positive effects, and provide potential targets for further study to determine if they can be used to treat SCI. Bourguignon, Lukas et al. systematically review the effect of drugs commonly administered after traumatic spinal cord injury on the neurological recovery in both animal studies and humans. Extensive heterogeneity in study characteristics and results highlight the need for harmonization across the field but also the potential for drug repurposing.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-13"},"PeriodicalIF":5.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514035","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}
Pub Date : 2024-10-23DOI: 10.1038/s43856-024-00629-1
Mridula Shankar, A. Metin Gülmezoglu, Joshua P. Vogel, Shivaprasad S. Goudar, Annie McDougall, Manjunath S. Somannavar, Sara Rushwan, Yeshita V. Pujar, Umesh Charantimath, Anne Ammerdorffer, Meghan A. Bohren
Systematic under-representation of pregnant women and gender diverse pregnant people in clinical research has prevented them from benefitting fairly from biomedical advances. The resulting lack of pharmacological safety and efficacy data leads to medicine discontinuation, sub-optimal dosing, and reliance on repurposed therapies. We identify four roadblocks to fair inclusion. First, investment and research are inhibited by protectionist attitudes among research gatekeepers who view pregnancy as a vulnerable state. Second, exclusion ignores human-specific biological variations affecting medication absorption and impacts on the pregnant body. Third, pregnant populations in low-and middle-income countries face a double disadvantage due to gender and location, despite bearing a disproportionate maternal mortality burden. Fourth, perspectives and experiences of pregnant populations are undervalued in clinical intervention design. We propose five actions to optimize fair inclusion: fostering reciprocal partnerships, prioritizing multi-disciplinary research, awareness-raising of the need for pharmaceutical innovation, conducting regulatory analyses, and promoting responsible inclusion over presumptive exclusion. Shankar et al. discuss how to better undertake research and assure health interests of pregnant women and gender diverse pregnant people. Their recommendations include growing research and regulatory partnerships and innovation, plus promoting responsible inclusion in place of presumptive exclusion.
{"title":"Eliminating gender bias in biomedical research requires fair inclusion of pregnant women and gender diverse people","authors":"Mridula Shankar, A. Metin Gülmezoglu, Joshua P. Vogel, Shivaprasad S. Goudar, Annie McDougall, Manjunath S. Somannavar, Sara Rushwan, Yeshita V. Pujar, Umesh Charantimath, Anne Ammerdorffer, Meghan A. Bohren","doi":"10.1038/s43856-024-00629-1","DOIUrl":"10.1038/s43856-024-00629-1","url":null,"abstract":"Systematic under-representation of pregnant women and gender diverse pregnant people in clinical research has prevented them from benefitting fairly from biomedical advances. The resulting lack of pharmacological safety and efficacy data leads to medicine discontinuation, sub-optimal dosing, and reliance on repurposed therapies. We identify four roadblocks to fair inclusion. First, investment and research are inhibited by protectionist attitudes among research gatekeepers who view pregnancy as a vulnerable state. Second, exclusion ignores human-specific biological variations affecting medication absorption and impacts on the pregnant body. Third, pregnant populations in low-and middle-income countries face a double disadvantage due to gender and location, despite bearing a disproportionate maternal mortality burden. Fourth, perspectives and experiences of pregnant populations are undervalued in clinical intervention design. We propose five actions to optimize fair inclusion: fostering reciprocal partnerships, prioritizing multi-disciplinary research, awareness-raising of the need for pharmaceutical innovation, conducting regulatory analyses, and promoting responsible inclusion over presumptive exclusion. Shankar et al. discuss how to better undertake research and assure health interests of pregnant women and gender diverse pregnant people. Their recommendations include growing research and regulatory partnerships and innovation, plus promoting responsible inclusion in place of presumptive exclusion.","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":" ","pages":"1-5"},"PeriodicalIF":5.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514029","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}
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