Pub Date : 2020-06-02DOI: 10.1080/21678707.2020.1784722
C. Kashtan
ABSTRACT Introduction This review presents an approach to early diagnosis and treatment of Alport syndrome, an important genetic cause of kidney failure, with the goal of delaying the need for dialysis and kidney transplantation. This approach is based on an expansive genetic definition of Alport syndrome designed to maximize the identification of affected individuals who may benefit from early intervention. Areas covered The areas discussed include the definition of Alport syndrome, estimating the risk and velocity of progression to kidney failure , the impact of early intervention on kidney outcomes, improving early diagnosis and treatment and hearing loss in Alport syndrome. The recommendations in this review are based on the author's reading and interpretation of approximately 1000 papers published on Alport syndrome since 2000 and archived on PubMed. Expert opinion It is by now clear that the natural history of Alport kidney disease can be substantially modified by angiotensin-converting enzyme (ACE) inhibition, and that optimal kidney outcomes are achieved by the initiation of treatment while kidney function is still normal. In the coming decade enhanced early diagnosis and treatment will continue to increase the age at onset of kidney failure in the Alport population. Novel therapies that can be added on to ACE inhibition will provide further benefit. Safe and effective curative therapies are not out of reach but there are significant hurdles to overcome to make such approaches a reality.
{"title":"An update on current and potential genetic insights and diagnosis of Alport syndrome","authors":"C. Kashtan","doi":"10.1080/21678707.2020.1784722","DOIUrl":"https://doi.org/10.1080/21678707.2020.1784722","url":null,"abstract":"ABSTRACT Introduction This review presents an approach to early diagnosis and treatment of Alport syndrome, an important genetic cause of kidney failure, with the goal of delaying the need for dialysis and kidney transplantation. This approach is based on an expansive genetic definition of Alport syndrome designed to maximize the identification of affected individuals who may benefit from early intervention. Areas covered The areas discussed include the definition of Alport syndrome, estimating the risk and velocity of progression to kidney failure , the impact of early intervention on kidney outcomes, improving early diagnosis and treatment and hearing loss in Alport syndrome. The recommendations in this review are based on the author's reading and interpretation of approximately 1000 papers published on Alport syndrome since 2000 and archived on PubMed. Expert opinion It is by now clear that the natural history of Alport kidney disease can be substantially modified by angiotensin-converting enzyme (ACE) inhibition, and that optimal kidney outcomes are achieved by the initiation of treatment while kidney function is still normal. In the coming decade enhanced early diagnosis and treatment will continue to increase the age at onset of kidney failure in the Alport population. Novel therapies that can be added on to ACE inhibition will provide further benefit. Safe and effective curative therapies are not out of reach but there are significant hurdles to overcome to make such approaches a reality.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"179 - 188"},"PeriodicalIF":0.8,"publicationDate":"2020-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1784722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48195854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-02DOI: 10.1080/21678707.2020.1780117
Talita Lemos Neves Barreto, Elaine Cristina de Almeida Kotchetkoff, C. Lago, R. Sarni
ABSTRACT Objective Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disease caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. The parents do not manifest the disease but are heterozygous carriers of a pathogenic ATM mutation that may be associated with coronary atherosclerosis and increased cholesterol levels. The objective of this study was to verify whether there is an agreement between the biomarkers of the lipid profile and the carotid intima-media thickness (IMT) of mothers and their children with A-T. Methods This cross-sectional study included A-T patients (n = 11), their mothers (n = 9), and controls (n = 20). Anthropometric data, lipid profile markers, and apolipoproteins (Apo) A-1 and B were collected and carotid IMT was performed. Results Dyslipidemia was found in 7/11 of patients with A-T and 6/9 of mothers with a strong level of agreement (po = 1.00; Kappa = 1.00;p = 0.001). Regarding the variables of the lipid profile, only NHDL-c (ICC = 0.64;p = 0.01) and the ApoB/ApoA-1 ratios (po = 0.72;Kappa = 0.14;p = 0.62) and TG/HDL-c (ICC = 0.54;p = 0.04) showed agreement between mothers and children. A significant difference (p < 0.001) of the carotid IMT was found in A-T patients when compared to their mothers. Conclusion The agreement for lipid metabolism biomarkers associated with cardiovascular risk between children with A-T and their mothers emphasizes the importance of continuous monitoring of both.
{"title":"Agreement of cardiovascular risk in ataxia-telangiectasia mutated heterozygotes and their children with Ataxia-telangiectasia","authors":"Talita Lemos Neves Barreto, Elaine Cristina de Almeida Kotchetkoff, C. Lago, R. Sarni","doi":"10.1080/21678707.2020.1780117","DOIUrl":"https://doi.org/10.1080/21678707.2020.1780117","url":null,"abstract":"ABSTRACT Objective Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disease caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. The parents do not manifest the disease but are heterozygous carriers of a pathogenic ATM mutation that may be associated with coronary atherosclerosis and increased cholesterol levels. The objective of this study was to verify whether there is an agreement between the biomarkers of the lipid profile and the carotid intima-media thickness (IMT) of mothers and their children with A-T. Methods This cross-sectional study included A-T patients (n = 11), their mothers (n = 9), and controls (n = 20). Anthropometric data, lipid profile markers, and apolipoproteins (Apo) A-1 and B were collected and carotid IMT was performed. Results Dyslipidemia was found in 7/11 of patients with A-T and 6/9 of mothers with a strong level of agreement (po = 1.00; Kappa = 1.00;p = 0.001). Regarding the variables of the lipid profile, only NHDL-c (ICC = 0.64;p = 0.01) and the ApoB/ApoA-1 ratios (po = 0.72;Kappa = 0.14;p = 0.62) and TG/HDL-c (ICC = 0.54;p = 0.04) showed agreement between mothers and children. A significant difference (p < 0.001) of the carotid IMT was found in A-T patients when compared to their mothers. Conclusion The agreement for lipid metabolism biomarkers associated with cardiovascular risk between children with A-T and their mothers emphasizes the importance of continuous monitoring of both.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"209 - 213"},"PeriodicalIF":0.8,"publicationDate":"2020-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1780117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43145586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-02DOI: 10.1080/21678707.2020.1784721
A. Marais, D. Blom, F. Raal
ABSTRACT Introduction Homozygous familial hypercholesterolemia (hoFH), a genetic disorder characterized by markedly impaired hepatic clearance of LDL and LDL cholesterol concentration exceeding 12 mmol/L, causes coronary artery and aortic valve disease before adulthood. The hoFH phenotype is mostly due to bi-allelic mutations in the LDL receptor gene. Areas covered HoFH as a clinical phenotype has distinct genetic causes which may affect response to treatment. The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and other physiologic processes including inflammation and sepsis. Strategies that may lower plasma PCSK9 activity so that uptake of plasma LDL into the liver is improved. Inclisiran, a synthetic oligonucleotide, specifically targets the liver to limit production of PCSK9. Adverse effects due to oligonucleotides in general and specific to low PCSK9 concentration are considered. Expert opinion HoFH requires expert diagnostic work-up for best management and prediction of response to treatment, including inclisiran. Though most hoFH patients will not reach the ideal LDL cholesterol concentration target by adding agents that lower PCSK9 activity to treatment with statins and ezetimibe, additional benefit is expected. Some patients may not respond. The safety to date appears good but patients with hoFH require treatment from childhood and long-term safety remains to be established.
{"title":"Homozygous familial hypercholesterolemia and its treatment by inclisiran","authors":"A. Marais, D. Blom, F. Raal","doi":"10.1080/21678707.2020.1784721","DOIUrl":"https://doi.org/10.1080/21678707.2020.1784721","url":null,"abstract":"ABSTRACT Introduction Homozygous familial hypercholesterolemia (hoFH), a genetic disorder characterized by markedly impaired hepatic clearance of LDL and LDL cholesterol concentration exceeding 12 mmol/L, causes coronary artery and aortic valve disease before adulthood. The hoFH phenotype is mostly due to bi-allelic mutations in the LDL receptor gene. Areas covered HoFH as a clinical phenotype has distinct genetic causes which may affect response to treatment. The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and other physiologic processes including inflammation and sepsis. Strategies that may lower plasma PCSK9 activity so that uptake of plasma LDL into the liver is improved. Inclisiran, a synthetic oligonucleotide, specifically targets the liver to limit production of PCSK9. Adverse effects due to oligonucleotides in general and specific to low PCSK9 concentration are considered. Expert opinion HoFH requires expert diagnostic work-up for best management and prediction of response to treatment, including inclisiran. Though most hoFH patients will not reach the ideal LDL cholesterol concentration target by adding agents that lower PCSK9 activity to treatment with statins and ezetimibe, additional benefit is expected. Some patients may not respond. The safety to date appears good but patients with hoFH require treatment from childhood and long-term safety remains to be established.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"197 - 208"},"PeriodicalIF":0.8,"publicationDate":"2020-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1784721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45840945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-02DOI: 10.1080/21678707.2020.1784720
S. Mariz, K. Westermark, B. Sepodes
ABSTRACT Introduction In the first 18 years of the implementation of the orphan medicinal products regulation, it has been noted that every year a steady number of orphan designations refer to new conditions, not designated previously. This is important because it offers documented evidence that research and development is ongoing for many areas of rare diseases. These newly designated rare conditions reflect drug development opportunities in areas of limited regulatory knowledge. Authors carried out a literature search via pubmed and Google as well as refering to previous articles they have been involved in as authors. Areas covered The aim of this paper is to review the outcomes associated with new rare conditions designation by the COMP. With over 2000 designations made since its creation data specific to conditions designation collected by the European Medicines Agency (EMA) after each monthly plenary session is presented here. The data is observational and has been grouped into therapeutic criteria based on ATC codes. Expert opinion Regulators should continue to engage in constructive dialogue with stakeholders so that the regulatory requirements are less of a hurdle and more of an opportunity to speed up drug development in areas of unmet medical need. The designation of new conditions further supports the utility, need, and meaning of the orphan regulation as a catalyst of drug development.
{"title":"Designation of orphan conditions in Europe: regulatory observations and considerations after implementation of regulation 141/2000","authors":"S. Mariz, K. Westermark, B. Sepodes","doi":"10.1080/21678707.2020.1784720","DOIUrl":"https://doi.org/10.1080/21678707.2020.1784720","url":null,"abstract":"ABSTRACT Introduction In the first 18 years of the implementation of the orphan medicinal products regulation, it has been noted that every year a steady number of orphan designations refer to new conditions, not designated previously. This is important because it offers documented evidence that research and development is ongoing for many areas of rare diseases. These newly designated rare conditions reflect drug development opportunities in areas of limited regulatory knowledge. Authors carried out a literature search via pubmed and Google as well as refering to previous articles they have been involved in as authors. Areas covered The aim of this paper is to review the outcomes associated with new rare conditions designation by the COMP. With over 2000 designations made since its creation data specific to conditions designation collected by the European Medicines Agency (EMA) after each monthly plenary session is presented here. The data is observational and has been grouped into therapeutic criteria based on ATC codes. Expert opinion Regulators should continue to engage in constructive dialogue with stakeholders so that the regulatory requirements are less of a hurdle and more of an opportunity to speed up drug development in areas of unmet medical need. The designation of new conditions further supports the utility, need, and meaning of the orphan regulation as a catalyst of drug development.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"189 - 196"},"PeriodicalIF":0.8,"publicationDate":"2020-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1784720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41559157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-03DOI: 10.1080/21678707.2020.1770080
M. Krishnan, C. Barnett
ABSTRACT Introduction HIV-associated pulmonary arterial hypertension (HIV-PAH) is an increasingly recognized complication of HIV, with a significant degree of associated morbidity and mortality. Given a wide array in the severity of clinical presentations, the prompt diagnosis and subsequent initiation of therapies has remained a challenge in this rare condition. Areas covered Diagnosis of HIV-PAH has been primarily established by transthoracic echocardiogram and right heart catheterization. There are several viral proteins that have been implicated in the pathogenesis of this condition that could be developed as either alternative or complimentary diagnostics in the evaluation of this condition. Therapy for HIV-PAH is centered on the management of HIV as well as the use of standard PAH therapies. The caveats in this distinct patient population include the consideration of drug-drug interactions of therapy with highly active antiretroviral therapy (HAART) and rare use of calcium channel blockers. Expert opinion Further research into the pathogenesis of HIV-PAH is warranted in order to develop diagnostics and therapy directed at the viral proteins implicated in this condition. This will be integral to the future evaluation and management of this unique patient population.
{"title":"Advances in the diagnosis and treatment of HIV-associated pulmonary arterial hypertension","authors":"M. Krishnan, C. Barnett","doi":"10.1080/21678707.2020.1770080","DOIUrl":"https://doi.org/10.1080/21678707.2020.1770080","url":null,"abstract":"ABSTRACT Introduction HIV-associated pulmonary arterial hypertension (HIV-PAH) is an increasingly recognized complication of HIV, with a significant degree of associated morbidity and mortality. Given a wide array in the severity of clinical presentations, the prompt diagnosis and subsequent initiation of therapies has remained a challenge in this rare condition. Areas covered Diagnosis of HIV-PAH has been primarily established by transthoracic echocardiogram and right heart catheterization. There are several viral proteins that have been implicated in the pathogenesis of this condition that could be developed as either alternative or complimentary diagnostics in the evaluation of this condition. Therapy for HIV-PAH is centered on the management of HIV as well as the use of standard PAH therapies. The caveats in this distinct patient population include the consideration of drug-drug interactions of therapy with highly active antiretroviral therapy (HAART) and rare use of calcium channel blockers. Expert opinion Further research into the pathogenesis of HIV-PAH is warranted in order to develop diagnostics and therapy directed at the viral proteins implicated in this condition. This will be integral to the future evaluation and management of this unique patient population.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"169 - 177"},"PeriodicalIF":0.8,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1770080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41483412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-03DOI: 10.1080/21678707.2020.1767586
G. Boleto, D. Saadoun, P. Cacoub
ABSTRACT Introduction Mixed cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification. Areas covered This review highlights key advances, recent clinical trial updates and ongoing studies on the management of persistent and refractory CryoVas. Therapeutic strategies and treatment agents to manage the disease are described. A literature review was performed by searching for available research studies published before January 2020 on the Medline (PubMed) database. Expert opinion Antiviral therapy with direct antiviral agents is the mainstay of treatment for patients with HCV-associated CryoVas. B-cell depleting strategies, mainly with rituximab, is the main therapeutic option in severe and refractory cases of infectious and noninfectious CryoVas. Ongoing trials are currently exploring other targeted biological treatments in this setting.
{"title":"Strategies to prevent persistent or relapsed mixed cryoglobulinemia","authors":"G. Boleto, D. Saadoun, P. Cacoub","doi":"10.1080/21678707.2020.1767586","DOIUrl":"https://doi.org/10.1080/21678707.2020.1767586","url":null,"abstract":"ABSTRACT Introduction Mixed cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification. Areas covered This review highlights key advances, recent clinical trial updates and ongoing studies on the management of persistent and refractory CryoVas. Therapeutic strategies and treatment agents to manage the disease are described. A literature review was performed by searching for available research studies published before January 2020 on the Medline (PubMed) database. Expert opinion Antiviral therapy with direct antiviral agents is the mainstay of treatment for patients with HCV-associated CryoVas. B-cell depleting strategies, mainly with rituximab, is the main therapeutic option in severe and refractory cases of infectious and noninfectious CryoVas. Ongoing trials are currently exploring other targeted biological treatments in this setting.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"137 - 143"},"PeriodicalIF":0.8,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1767586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44703781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-03DOI: 10.1080/21678707.2020.1769598
T. Dassios, Hemant Ambulkar, A. Greenough
ABSTRACT Introduction Respiratory distress syndrome (RDS) remains an important problem. Identifying effective treatments and respiratory support modes is essential. Areas covered Current treatments and respiratory support modes and the evidence base for new therapies and respiratory modes have been examined. Methods A literature search was undertaken using PubMed and Google Scholar. Expert opinion It is now common to stabilise infants on non-invasive respiratory support in the delivery suite and give early selective surfactant to infants with RDS. Increasingly, less invasive surfactant administration is used. Systemically administered corticosteroids should not be given in the perinatal period; inhaled budesonide has been associated with an increased mortality. Inhaled nitric oxide can be helpful in preterm infants with pulmonary hypertension. Caffeine should be routinely administered. Further research regarding stems cells is required. Post extubation, nasal intermittent positive pressure ventilation (NIPPV) rather than nasal continuous positive airway pressure (nCPAP) provides better support and humidified high flow nasal cannula (HHFNC) has similar efficacy to continuous positive airway pressure (CPAP). Volume targeting should be used for infants requiring intubation. There is insufficient evidence to determine the role of neurally adjusted ventilatory assist or whether closed loop automatic oxygen control improves long term outcomes.
{"title":"Treatment and respiratory support modes for neonates with respiratory distress syndrome","authors":"T. Dassios, Hemant Ambulkar, A. Greenough","doi":"10.1080/21678707.2020.1769598","DOIUrl":"https://doi.org/10.1080/21678707.2020.1769598","url":null,"abstract":"ABSTRACT Introduction Respiratory distress syndrome (RDS) remains an important problem. Identifying effective treatments and respiratory support modes is essential. Areas covered Current treatments and respiratory support modes and the evidence base for new therapies and respiratory modes have been examined. Methods A literature search was undertaken using PubMed and Google Scholar. Expert opinion It is now common to stabilise infants on non-invasive respiratory support in the delivery suite and give early selective surfactant to infants with RDS. Increasingly, less invasive surfactant administration is used. Systemically administered corticosteroids should not be given in the perinatal period; inhaled budesonide has been associated with an increased mortality. Inhaled nitric oxide can be helpful in preterm infants with pulmonary hypertension. Caffeine should be routinely administered. Further research regarding stems cells is required. Post extubation, nasal intermittent positive pressure ventilation (NIPPV) rather than nasal continuous positive airway pressure (nCPAP) provides better support and humidified high flow nasal cannula (HHFNC) has similar efficacy to continuous positive airway pressure (CPAP). Volume targeting should be used for infants requiring intubation. There is insufficient evidence to determine the role of neurally adjusted ventilatory assist or whether closed loop automatic oxygen control improves long term outcomes.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"145 - 156"},"PeriodicalIF":0.8,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1769598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49520320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-03DOI: 10.1080/21678707.2020.1770079
D. Wendel, B. E. Ho, Tanyaporn K Kaenkumchorn, S. Horslen
ABSTRACT Introduction Short bowel syndrome (SBS) is the most common cause of intestinal failure resulting in the need for long-term parenteral nutrition. Treatment for SBS involves the close management of parenteral and enteral nutrition as well as central venous access to prevent complications while allowing time for the remaining intestine to undergo the process of adaptation. Areas covered This review highlights the current state of management and treatment of SBS. Parenteral and enteral management strategies are outlined with a review of the evidence regarding lipid management, prevention of intestinal failure associated liver disease, and promotion of intestinal adaptation. Central venous access management and the evidence for prevention of central line-associated blood stream infections are reviewed. The most common nutritional deficiencies and complications associated with SBS are discussed and treatment strategies covered. Several hormone analogues have recently been developed which have been shown to promote intestinal adaptation. The evidence for these new drugs is also outlined. Expert opinion Previous treatments for SBS focused on symptom management and complication prevention. While these remain important in the intestinal rehabilitation of patients with SBS, the introduction of promising new hormonal therapies has provided a way to augment the process of adaptation.
{"title":"Advances in non-surgical treatment for pediatric patients with short bowel syndrome","authors":"D. Wendel, B. E. Ho, Tanyaporn K Kaenkumchorn, S. Horslen","doi":"10.1080/21678707.2020.1770079","DOIUrl":"https://doi.org/10.1080/21678707.2020.1770079","url":null,"abstract":"ABSTRACT Introduction Short bowel syndrome (SBS) is the most common cause of intestinal failure resulting in the need for long-term parenteral nutrition. Treatment for SBS involves the close management of parenteral and enteral nutrition as well as central venous access to prevent complications while allowing time for the remaining intestine to undergo the process of adaptation. Areas covered This review highlights the current state of management and treatment of SBS. Parenteral and enteral management strategies are outlined with a review of the evidence regarding lipid management, prevention of intestinal failure associated liver disease, and promotion of intestinal adaptation. Central venous access management and the evidence for prevention of central line-associated blood stream infections are reviewed. The most common nutritional deficiencies and complications associated with SBS are discussed and treatment strategies covered. Several hormone analogues have recently been developed which have been shown to promote intestinal adaptation. The evidence for these new drugs is also outlined. Expert opinion Previous treatments for SBS focused on symptom management and complication prevention. While these remain important in the intestinal rehabilitation of patients with SBS, the introduction of promising new hormonal therapies has provided a way to augment the process of adaptation.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"157 - 168"},"PeriodicalIF":0.8,"publicationDate":"2020-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1770079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42255213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-02DOI: 10.1080/21678707.2020.1758061
Mohammad Ridwane Mungroo, N. Khan, R. Siddiqui
ABSTRACT Introduction: Balamuthia mandrillaris is known to cause a fatal infection of the central nervous system termed granulomatous amoebic encephalitis (GAE). Cases of GAE by B. mandrillaris are usually fatal indicating the inefficacy of currently available regimens used to treat the disease and the virulent nature of the amoebae. Areas covered: This review discusses the current treatment options, diagnosis, and pathogenesis of Balamuthia mandrillaris. In this regard, a PubMed search using pathogenesis, treatment, and diagnosis, combined with B. mandrillaris as keywords, was performed. In addition, conference proceedings, and discussions in Free-Living-Amoebae meetings over the past 20 years were reviewed. Expert opinion: Despite the current treatment and diagnostic options, the mortality rates due to B. mandrillaris infections remain alarmingly high. The actual number of GAE cases due to B. mandrillaris are much higher than the currently reported number. Information on the pathogenesis of the amoebae is limited, highlighting the need for further studies on the pathogenesis of B. mandrillaris. This would provide useful information to improve both diagnostic and treatment options. Similarly, new molecules that are targeted toward B. mandrillaris and can penetrate the blood-brain barrier should be established. Theranostics may be the way forward for the treatment of B. mandrillaris.
{"title":"Balamuthia mandrillaris: pathogenesis, diagnosis, and treatment","authors":"Mohammad Ridwane Mungroo, N. Khan, R. Siddiqui","doi":"10.1080/21678707.2020.1758061","DOIUrl":"https://doi.org/10.1080/21678707.2020.1758061","url":null,"abstract":"ABSTRACT Introduction: Balamuthia mandrillaris is known to cause a fatal infection of the central nervous system termed granulomatous amoebic encephalitis (GAE). Cases of GAE by B. mandrillaris are usually fatal indicating the inefficacy of currently available regimens used to treat the disease and the virulent nature of the amoebae. Areas covered: This review discusses the current treatment options, diagnosis, and pathogenesis of Balamuthia mandrillaris. In this regard, a PubMed search using pathogenesis, treatment, and diagnosis, combined with B. mandrillaris as keywords, was performed. In addition, conference proceedings, and discussions in Free-Living-Amoebae meetings over the past 20 years were reviewed. Expert opinion: Despite the current treatment and diagnostic options, the mortality rates due to B. mandrillaris infections remain alarmingly high. The actual number of GAE cases due to B. mandrillaris are much higher than the currently reported number. Information on the pathogenesis of the amoebae is limited, highlighting the need for further studies on the pathogenesis of B. mandrillaris. This would provide useful information to improve both diagnostic and treatment options. Similarly, new molecules that are targeted toward B. mandrillaris and can penetrate the blood-brain barrier should be established. Theranostics may be the way forward for the treatment of B. mandrillaris.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"8 1","pages":"111 - 119"},"PeriodicalIF":0.8,"publicationDate":"2020-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1758061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46554999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-02DOI: 10.1080/21678707.2020.1751122
R. Pignolo, F. Kaplan
ABSTRACT Introduction: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by heterotopic ossification, congenital skeletal abnormalities especially of the great toes, and several features of accelerated aging. Missense mutations in the in the gene for ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor are responsible for all known cases of FOP. Progression of the condition is relentless and occurs clinically via episodic inflammatory exacerbations or flare-ups and/or spontaneously (without flare-ups). Areas covered: The current pharmacological targets, potential designs for clinical trials, and possible treatment approaches using experimental and repurposed agents for FOP are reviewed [PubMed 2000–2019, using FOP as a key search term]. Expert opinion: The growing number of pharmacological interventions for FOP includes blocking the activity of the mutant FOP receptor, quenching inflammatory triggers, inhibiting connective tissue progenitor cells that give rise to ectopic endochondral ossification, and minimizing the micro-environmental factors that promote lesion progression. In light of the rarity of FOP, new approaches to clinical trial design, including delayed start and n = 1 designs, are considered. Finally, a schema for pharmacological management of FOP in anticipation of approved medications and the availability of repurposed drugs is proposed.
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