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Diseases, Volume 6, Issue 2 (June 2018)

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Cover Story (view full-size image) Aspergillosis of the central nervous system is an uncommon complication following neurosurgical [...] Read more.
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Open AccessFeature PaperReview Renal Impairment in Chronic Hepatitis B: A Review
Received: 15 May 2018 / Revised: 4 June 2018 / Accepted: 4 June 2018 / Published: 19 June 2018
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Abstract
The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver
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The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver and is involved in liver diseases. Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. Nucleos(t)ide analog (NA) therapy effectively suppresses HBV replication by inhibiting HBV polymerase, thus decreasing the levels of serum HBV-DNA and delaying the progression of cirrhosis. Although NA therapy is recommended for all patients with chronic HBV infection, regardless of the level of renal dysfunction, there is limited information on NA use in patients with chronic kidney disease. In addition, in patients with end-stage liver cirrhosis, hepatorenal syndrome can be fatal. Hence, we should take into account the stage of impaired renal function in patients with cirrhosis. The aims of this article are to review the epidemiology, clinical presentation, treatment, and prevention of HBV-associated nephropathy. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
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Open AccessCommunication Adverse Effects of Direct Acting Antivirals in HIV/HCV Coinfected Patients: A 4-Year Experience in Miami, Florida
Received: 24 May 2018 / Revised: 16 June 2018 / Accepted: 18 June 2018 / Published: 19 June 2018
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Abstract
Introduction: The new direct acting antivirals (DAA) have demonstrated low rates of adverse effects in controlled studies. However, real world-studies have disclosed emerging toxicities and drug-drug interactions in special populations. Methods: We conducted a retrospective review of HIV/HCV coinfected patients who were treated
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Introduction: The new direct acting antivirals (DAA) have demonstrated low rates of adverse effects in controlled studies. However, real world-studies have disclosed emerging toxicities and drug-drug interactions in special populations. Methods: We conducted a retrospective review of HIV/HCV coinfected patients who were treated with DAA at Jackson Memorial Hospital from 2014 to 2017. Our aim was to determine the adverse effects (AE) and factors that are associated with AE in HIV/HCV individuals who are treated with DAA. Results: There were 78 coinfected patients treated with DAA. AE that were secondary to DAA were reported by 21 (26.9%) patients. The most common AE were fatigue (47.6%), gastrointestinal symptoms (38.1%), anemia (14.3%), and headache (14.3%). In comparison with the rest of the study cohort, the patients who developed AE were more often Caucasian (33.3% vs. 10.5%, p = 0.017) and were more frequently treated with PrOD/Ribavirin (9.5% vs. 0%, p = 0.018). In terms of antiretroviral therapy (ART), there was a trend towards a more frequent use of TDF/FTC + NNRTI (33.3% vs. 14%, p = 0.055). Conclusions: These findings demonstrated good tolerability of DAAs in HIV/HCV coinfected patients. More real-world studies are needed to explore the variables that are associated with AE. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
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Open AccessReview Pancreatic Cystic Lesions: Pathogenesis and Malignant Potential
Received: 15 May 2018 / Revised: 6 June 2018 / Accepted: 7 June 2018 / Published: 13 June 2018
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Abstract
Pancreatic cancer remains one of the most lethal cancers despite extensive research. Further understanding of precursor lesions may enhance the ability to treat and prevent pancreatic cancer. Pancreatic cystic lesions (PCLs) with malignant potential include: mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous
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Pancreatic cancer remains one of the most lethal cancers despite extensive research. Further understanding of precursor lesions may enhance the ability to treat and prevent pancreatic cancer. Pancreatic cystic lesions (PCLs) with malignant potential include: mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasm), solid pseudopapillary tumors and cystic neuroendocrine tumors. This review summarizes the latest literature describing what is known about the pathogenesis and malignant potential of these PCLs, including unique epidemiological, radiological, histological, genetic and molecular characteristics. Full article
(This article belongs to the Special Issue Pathogenesis of Pancreatic Cancer)
Open AccessArticle Prevalence and Determinants of Antibiotic Self-Medication among Adult Patients with Respiratory Tract Infections in the Mboppi Baptist Hospital, Douala, Cameroon: A Cross-Sectional Study
Received: 30 April 2018 / Revised: 4 June 2018 / Accepted: 7 June 2018 / Published: 8 June 2018
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Abstract
Antibiotic self-medication in patients with respiratory tract infections (RTI) is increasing globally and has been reported to be one of the prime contributors to antimicrobial resistance (AMR). Our study aims to provide data on the prevalence of antibiotic self-medication and identify the factors
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Antibiotic self-medication in patients with respiratory tract infections (RTI) is increasing globally and has been reported to be one of the prime contributors to antimicrobial resistance (AMR). Our study aims to provide data on the prevalence of antibiotic self-medication and identify the factors contributing to self-medication in adult patients with respiratory tract infection in an urban setting in Cameroon. This was cross-sectional study carried out at Mboppi Baptist Hospital, Douala, Cameroon. A validated structured questionnaire was administered to 308 consenting participants with diagnosed RTIs, to collect data on socio-demographic characteristics and history of antibiotic self-medication. Significance was set at a p-value < 0.05. The prevalence of antibiotic self-medication amongst individuals with RTIs was 41.9% (95% CI 36.5% to 47.5%). Patients with a history of pulmonary tuberculosis (TB) were significantly less likely to self-medicate with antibiotics (p-value = 0.043). The most common source of antibiotic self-medication was pharmacies (62%) and Cotrimoxazole and Amoxicillin were the most commonly used antibiotics (38.8% (50), 26.4% (34), respectively). Self-medication with antibiotics in adult patients with RTIs is common in Cameroon. Control of the use of antibiotics, organisation of medication stewardship programs, and education of the general population on the adverse consequences of antibiotic self-medication are required. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessReview Treatment of Major Depressive Disorder in Pediatric Populations
Received: 30 April 2018 / Revised: 28 May 2018 / Accepted: 31 May 2018 / Published: 4 June 2018
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Abstract
Major depressive disorder (MDD) is a severe illness that afflicts about 16.6% of people over their lifetime. MDD is highly correlated with suicidality, and often first presents in adolescence. Unfortunately, many pediatric patients suffering from MDD go undiagnosed, and current evidence-based treatment options
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Major depressive disorder (MDD) is a severe illness that afflicts about 16.6% of people over their lifetime. MDD is highly correlated with suicidality, and often first presents in adolescence. Unfortunately, many pediatric patients suffering from MDD go undiagnosed, and current evidence-based treatment options in the U.S. are limited to psychotherapy and two selective serotonin reuptake inhibitors approved by the United States Food and Drug Administration. Molecular mechanisms have been shown to play a role in MDD pathogenesis, progression, and response to medication, yet few studies have explored the role of these pathways in pediatric MDD. In this review, we outline the gravity and importance of MDD in pediatric patients, some challenges in diagnosis and treatment, current treatments available for pediatric patients, and research to investigate differences between pediatric and adult MDD. We hope that this review will provide an outline of the current understanding and treatment of MDD in pediatric patients, and provide thoughtful insights for future work that could advance our understanding of MDD in pediatric populations, and also identify new therapeutic strategies. Full article
(This article belongs to the Special Issue Pediatric Diseases)
Open AccessFeature PaperReview Psoriasis and Microbiota: A Systematic Review
Received: 5 May 2018 / Revised: 29 May 2018 / Accepted: 1 June 2018 / Published: 2 June 2018
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Abstract
Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy,
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Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. Aim: Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. Conclusions: Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
Open AccessCase Report Central Nervous System Aspergillosis: An Unexpected Complication following Neurosurgery
Received: 19 May 2018 / Revised: 29 May 2018 / Accepted: 30 May 2018 / Published: 31 May 2018
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Abstract
Post-surgical aspergillosis is an uncommon complication that carries a high mortality rate in affected patients. The diagnosis is challenging given the lack of highly sensitive methods to isolate Aspergillus from surgical sites. Here, we present a case of post-surgical aspergillosis that occurred after
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Post-surgical aspergillosis is an uncommon complication that carries a high mortality rate in affected patients. The diagnosis is challenging given the lack of highly sensitive methods to isolate Aspergillus from surgical sites. Here, we present a case of post-surgical aspergillosis that occurred after the resection of acoustic neuroma in an immunocompetent patient. Imaging revealed leptomeningeal enhancement and a cerebellar extra-axial fluid collection adjacent to the right retrosigmoid craniotomy. The patient was taken to the operating room for debridement, where purulent fluid was obtained from subdural space. The diagnosis was achieved by histopathology and polymerase chain reaction (PCR) in brain tissue. Appropriate investigations failed to detect contamination in the operating room. The patient was successfully treated with 3 months of voriconazole. We highlight the importance of recognizing this uncommon complication and advocate for the use of molecular techniques to improve the diagnostic yield in central nervous system aspergillosis. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessReview CVD Risk Stratification in the PCSK9 Era: Is There a Role for LDL Subfractions?
Received: 4 May 2018 / Revised: 23 May 2018 / Accepted: 24 May 2018 / Published: 27 May 2018
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Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce the risk of cardiovascular events and all-cause mortality in patients at high risk of cardiovascular disease (CVD). Due to high costs and unknown long-term adverse effects, critical evaluation of patients considered for PCSK9 inhibitors is
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce the risk of cardiovascular events and all-cause mortality in patients at high risk of cardiovascular disease (CVD). Due to high costs and unknown long-term adverse effects, critical evaluation of patients considered for PCSK9 inhibitors is important. It has been proposed that measuring low-density lipoprotein (LDL) subfractions, or LDL particle numbers (LDL-P), could be of value in CVD risk assessment and may identify patients at high risk of CVD. This review evaluates the evidence for the use of LDL subfractions, or LDL-P, when assessing CVD risk in patients for whom PCSK9 inhibitors are considered as a lipid-lowering therapy. Numerous methods for measuring LDL subfractions and LDL-P are available, but several factors limit their availability. A lack of standardization makes comparison between the different methods challenging. Longitudinal population-based studies have found an independent association between different LDL subfractions, LDL-P, and an increased risk of cardiovascular events, but definitive evidence that these measurements add predictive value to the standard risk markers is lacking. No studies have proven that these measurements improve clinical outcomes. PCSK9 inhibitors seem to be effective at lowering all LDL subfractions and LDL-P, but any evidence that measuring LDL subfractions and LDL-P yield clinically useful information is lacking. Such analyses are currently not recommended when considering whether to initiate PCKS9 inhibitors in patients at risk of CVD. Full article
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Open AccessFeature PaperReview Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment
Received: 3 May 2018 / Revised: 22 May 2018 / Accepted: 22 May 2018 / Published: 24 May 2018
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Abstract
Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their
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Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development. Full article
Open AccessReview Zebrafish Models of Rare Hereditary Pediatric Diseases
Received: 27 April 2018 / Revised: 17 May 2018 / Accepted: 19 May 2018 / Published: 22 May 2018
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Abstract
Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even
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Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even when the mapping results are unambiguous, the affected gene might be of unknown function. In these cases, understanding how a particular genotype can result in a phenotype also needs carefully designed experimental work. Model organism genetics can offer a straightforward experimental setup for hypothesis testing. Containing orthologs for over 80% of the genes involved in human diseases, zebrafish (Danio rerio) has emerged as one of the top disease models over the past decade. A plethora of genetic tools makes it easy to create mutations in almost any gene of the zebrafish genome and these mutant strains can be used in high-throughput preclinical screens for active molecules. As this small vertebrate species offers several other advantages as well, its popularity in biomedical research is bound to increase, with “aquarium to bedside” drug development pipelines taking a more prevalent role in the near future. Full article
(This article belongs to the Special Issue Pediatric Diseases)
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Open AccessFeature PaperReview Viral Vectors in Gene Therapy
Received: 30 April 2018 / Revised: 15 May 2018 / Accepted: 16 May 2018 / Published: 21 May 2018
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Abstract
Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Significant improvements in vector engineering, delivery, and safety have placed viral vector-based therapy at the forefront of modern medicine. Viral vectors have been employed for the treatment
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Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Significant improvements in vector engineering, delivery, and safety have placed viral vector-based therapy at the forefront of modern medicine. Viral vectors have been employed for the treatment of various diseases such as metabolic, cardiovascular, muscular, hematologic, ophthalmologic, and infectious diseases and different types of cancer. Recent development in the area of immunotherapy has provided both preventive and therapeutic approaches. Furthermore, gene silencing generating a reversible effect has become an interesting alternative, and is well-suited for delivery by viral vectors. A number of preclinical studies have demonstrated therapeutic and prophylactic efficacy in animal models and furthermore in clinical trials. Several viral vector-based drugs have also been globally approved. Full article
(This article belongs to the Special Issue Gene Therapy)
Open AccessReview Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
Received: 29 April 2018 / Revised: 17 May 2018 / Accepted: 18 May 2018 / Published: 19 May 2018
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Abstract
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising
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Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell. This drug was intended as a solution to T cell deficient diseases such as B cell leukemia and autoimmune diseases such as rheumatoid arthritis. When phase I clinical trials were conducted, all volunteers that received the drug experienced severe cytokine release syndrome (CRS) and faced multiple-organ failure within hours. TGN1412 was reassessed and re-entered clinical trials as a therapeutic for rheumatoid arthritis. A new assay was developed to better quantify T cell response, and volunteers in this trial experienced no pro-inflammatory cytokine release. This essay analyzes how misinformation contributed to the failure of TGN1412 in clinical trials and how revisiting this therapeutic could yield a novel treatment for pediatric B cell leukemia. Full article
(This article belongs to the Special Issue Pediatric Diseases)
Open AccessCase Report Case Report of Isoniazid-Related Acute Liver Failure Requiring Liver Transplantation
Received: 2 May 2018 / Revised: 17 May 2018 / Accepted: 17 May 2018 / Published: 19 May 2018
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Abstract
The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4–4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens
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The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4–4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases. We report a case of a 67-year old male who developed subacute hepatic injury secondary to INH treatment for LTBI, and ultimately underwent liver transplantation due to the progression to hepatic decompensation, despite withdrawal of the medication. Because symptoms of INH hepatotoxicity are nonspecific and prognosis can be variable, clinicians must maintain a high index of suspicion for this adverse effect. As exemplified by this case, early recognition may be life-saving. Full article
(This article belongs to the Section Gastroenterology)
Open AccessCommentary Heat Shock Gene Inactivation and Protein Aggregation with Links to Chronic Diseases
Received: 10 April 2018 / Revised: 14 May 2018 / Accepted: 16 May 2018 / Published: 18 May 2018
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Abstract
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and
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The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer’s disease. Nutritional therapy is critical to prevent immunosenescence, and plasma Sirtuin 1 levels should be determined to reverse, stabilize, and prevent protein aggregation with relevance to mitochondrial apoptosis and programmed cell death in chronic diseases. Full article
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Open AccessFeature PaperReview Pulmonary Arterial Hypertension: Pathophysiology and Treatment
Received: 27 April 2018 / Revised: 12 May 2018 / Accepted: 12 May 2018 / Published: 16 May 2018
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Abstract
Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and
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Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and subsequent pulmonary arterial pressure, causing right ventricular failure which leads to eventual death if untreated. The management of PAH has advanced rapidly in recent years due to improved understanding of the condition’s pathophysiology, specifically the nitric oxide, prostacyclin-thromboxane and endothelin-1 pathways. Five classes of drugs targeting these pathways are now available: phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, prostacyclin receptor agonists and endothelin receptor antagonists. These developments have led to substantial improvements in mortality rate in recent decades. Recently, long-term studies have demonstrated sustained progression-free survival and have created a new paradigm of initial combination therapy. Despite these targeted therapies, PAH is still associated with significant morbidity and mortality. As such, further research into broadening our understanding of PAH pathophysiology is underway with potential of increasing the repertoire of drugs available. Full article
(This article belongs to the Section Cardiology)
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