Pub Date : 2024-06-20DOI: 10.1038/s41572-024-00526-w
Hannes Gatterer, Francisco C Villafuerte, Silvia Ulrich, Sanjeeb S Bhandari, Linda E Keyes, Martin Burtscher
Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood-brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.
{"title":"Altitude illnesses.","authors":"Hannes Gatterer, Francisco C Villafuerte, Silvia Ulrich, Sanjeeb S Bhandari, Linda E Keyes, Martin Burtscher","doi":"10.1038/s41572-024-00526-w","DOIUrl":"https://doi.org/10.1038/s41572-024-00526-w","url":null,"abstract":"<p><p>Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood-brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":null,"pages":null},"PeriodicalIF":76.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-13DOI: 10.1038/s41572-024-00525-x
Luca Pagliaro, Sai-Juan Chen, Daniel Herranz, Cristina Mecucci, Christine J Harrison, Charles G Mullighan, Ming Zhang, Zhu Chen, Nicolas Boissel, Stuart S Winter, Giovanni Roti
Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.
急性淋巴细胞白血病(ALL)是一种以未成熟淋巴细胞失控增殖为特征的血液恶性肿瘤。过去几十年来,人们在了解急性淋巴细胞白血病的生物学特性方面取得了重大进展,从而在诊断、治疗和监测方面取得了显著进步。自化疗出现以来,ALL 已成为检验适用于一般癌症的创新方法的平台。例如,全息医学的出现使人们对 ALL 的分子和遗传特征有了更深入的了解。基因组剖析技术的创新确定了驱动 ALL 的特定基因改变和突变,激发了新疗法的灵感。酪氨酸激酶抑制剂和免疫疗法等靶向药物已在亚组患者中显示出良好疗效,同时将不良反应降至最低。此外,嵌合抗原受体T细胞疗法的开发是ALL治疗领域的一大突破,它能带来显著的疗效,并有可能长期缓解病情。进步不仅限于治疗方式。可测量的残留疾病监测和体内外药物反应谱筛查可以更早地发现疾病复发并识别特殊反应者,从而使临床医生能够针对不同患者调整治疗策略。数十年的支持性和预防性护理改善了治疗相关并发症的管理,提高了 ALL 患者的生活质量。
{"title":"Acute lymphoblastic leukaemia.","authors":"Luca Pagliaro, Sai-Juan Chen, Daniel Herranz, Cristina Mecucci, Christine J Harrison, Charles G Mullighan, Ming Zhang, Zhu Chen, Nicolas Boissel, Stuart S Winter, Giovanni Roti","doi":"10.1038/s41572-024-00525-x","DOIUrl":"10.1038/s41572-024-00525-x","url":null,"abstract":"<p><p>Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":null,"pages":null},"PeriodicalIF":76.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-30DOI: 10.1038/s41572-024-00523-z
Sait Ashina, Carrie E Robertson, Anan Srikiatkhachorn, Giulia Di Stefano, Anne Donnet, Mojgan Hodaie, Mark Obermann, Marcela Romero-Reyes, Young Seok Park, Giorgio Cruccu, Lars Bendtsen
Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.
{"title":"Trigeminal neuralgia.","authors":"Sait Ashina, Carrie E Robertson, Anan Srikiatkhachorn, Giulia Di Stefano, Anne Donnet, Mojgan Hodaie, Mark Obermann, Marcela Romero-Reyes, Young Seok Park, Giorgio Cruccu, Lars Bendtsen","doi":"10.1038/s41572-024-00523-z","DOIUrl":"10.1038/s41572-024-00523-z","url":null,"abstract":"<p><p>Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":null,"pages":null},"PeriodicalIF":81.5,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.1038/s41572-024-00521-1
Lars B Dahlin, Malin Zimmerman, Maurizio Calcagni, Caroline A Hundepool, Nens van Alfen, Kevin C Chung
Carpal tunnel syndrome (CTS) is the most common nerve entrapment disorder worldwide. The epidemiology and risk factors, including family burden, for developing CTS are multi-factorial. Despite much research, its intricate pathophysiological mechanism(s) are not fully understood. An underlying subclinical neuropathy may indicate an increased susceptibility to developing CTS. Although surgery is often performed for CTS, clear international guidelines to indicate when to perform non-surgical or surgical treatment, based on stage and severity of CTS, remain to be elucidated. Neurophysiological examination, using electrophysiology or ultrasonography, performed in certain circumstances, should correlate with the history and findings in clinical examination of the person with CTS. History and clinical examination are particularly relevant globally owing to lack of other equipment. Various instruments are used to assess CTS and treatment outcomes as well as the effect of the disorder on quality of life. The surgical treatment options of CTS - open or endoscopic - offer an effective solution to mitigate functional impairments and pain. However, there are risks of post-operative persistent or recurrent symptoms, requiring meticulous diagnostic re-evaluation before any additional surgery. Health-care professionals should have increased awareness about CTS and all its implications. Future considerations of CTS include use of linked national registries to understand risk factors, explore possible screening methods, and evaluate diagnosis and treatment with a broader perspective beyond surgery, including psychological well-being.
{"title":"Carpal tunnel syndrome.","authors":"Lars B Dahlin, Malin Zimmerman, Maurizio Calcagni, Caroline A Hundepool, Nens van Alfen, Kevin C Chung","doi":"10.1038/s41572-024-00521-1","DOIUrl":"10.1038/s41572-024-00521-1","url":null,"abstract":"<p><p>Carpal tunnel syndrome (CTS) is the most common nerve entrapment disorder worldwide. The epidemiology and risk factors, including family burden, for developing CTS are multi-factorial. Despite much research, its intricate pathophysiological mechanism(s) are not fully understood. An underlying subclinical neuropathy may indicate an increased susceptibility to developing CTS. Although surgery is often performed for CTS, clear international guidelines to indicate when to perform non-surgical or surgical treatment, based on stage and severity of CTS, remain to be elucidated. Neurophysiological examination, using electrophysiology or ultrasonography, performed in certain circumstances, should correlate with the history and findings in clinical examination of the person with CTS. History and clinical examination are particularly relevant globally owing to lack of other equipment. Various instruments are used to assess CTS and treatment outcomes as well as the effect of the disorder on quality of life. The surgical treatment options of CTS - open or endoscopic - offer an effective solution to mitigate functional impairments and pain. However, there are risks of post-operative persistent or recurrent symptoms, requiring meticulous diagnostic re-evaluation before any additional surgery. Health-care professionals should have increased awareness about CTS and all its implications. Future considerations of CTS include use of linked national registries to understand risk factors, explore possible screening methods, and evaluate diagnosis and treatment with a broader perspective beyond surgery, including psychological well-being.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":null,"pages":null},"PeriodicalIF":76.9,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1038/s41572-024-00519-9
K. Kahle, Petra M. Klinge, Jenna E. Koschnitzky, Abhaya V. Kulkarni, Nanna MacAulay, Shenandoah Robinson, Steven J. Schiff, J. Strahle
{"title":"Paediatric hydrocephalus","authors":"K. Kahle, Petra M. Klinge, Jenna E. Koschnitzky, Abhaya V. Kulkarni, Nanna MacAulay, Shenandoah Robinson, Steven J. Schiff, J. Strahle","doi":"10.1038/s41572-024-00519-9","DOIUrl":"https://doi.org/10.1038/s41572-024-00519-9","url":null,"abstract":"","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":null,"pages":null},"PeriodicalIF":81.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140967670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}