scholarly journals Novel Insights into the Pathogenesis and Prevention of Intradialytic Hypotension

2018 ◽  
Vol 45 (1-3) ◽  
pp. 230-235 ◽  
Author(s):  
Frank M. van der Sande ◽  
Marijke J.  Dekker ◽  
Karel M.L. Leunissen ◽  
Jeroen P. Kooman
Keyword(s):  
Tissue Perfusion ◽  
Organ Damage ◽  
Adverse Outcomes ◽  
Fine Tuning ◽  
Great Promise ◽  
Intradialytic Hypotension ◽  
Related Factors ◽  
Thermally Induced ◽  
Discontinuous Nature

Background: Intradialytic hypotension (IDH) is a common complication of haemodialysis (HD) and associated with adverse outcomes, especially when a nadir definition (systolic blood pressure <90 mm Hg) is used. The pathogenesis of IDH is directly linked to the discontinuous nature of the HD treatment, in combination with patient-related factors such as age, diabetes mellitus and cardiac failure. Summary: Although the decline in blood volume due to removal of fluid by ultrafiltration is the prime mover, thermally induced reflex vasodilation compromises the haemodynamic response to hypovolemia. Recent studies have stressed the relevance of changes in tissue perfusion during HD, which may translate in long-term organ damage. Monitoring changes in tissue perfusion, for which emerging evidence becomes available, appears to have great promise in the fine-tuning of the dialysis procedure. Key Messages: While it is unlikely that IDH can be completely prevented, reduction in inter-dialytic weight gain, prevention of an increase in core temperature by adjusting the dialysate temperature and more frequent or prolonged dialysis treatment remain cornerstones in providing a more comfortable and safe treatment.

scholarly journals Optimized cell culture conditions promote ex-vivo manipulation and expansion of primitive hematopoietic stem cells for therapeutic gene editing.

2022 ◽  
Author(s):  
Rajeev Rai ◽  
Winston Vetharoy ◽  
Asma Naseem ◽  
Zohar Steinberg ◽  
Adrian James Thrasher ◽  
...  
Keyword(s):  
Gene Editing ◽  
Culture Media ◽  
Ex Vivo ◽  
Culture Conditions ◽  
Fine Tuning ◽  
Great Promise ◽  
Hematopoietic Stem ◽  
Monogenic Diseases

During the last few years, gene editing has emerged as a powerful tool for the therapeutic correction of monogenic diseases. CRISPR/Cas9 applied to hematopoietic stem and progenitor cells (HSPCs) has shown great promise in proof-of-principle preclinical studies to treat haematological disorders, and clinical trials using these tools are now underway. Nonetheless, there remain important challenges that need to be addressed, such as the efficiency of targeting primitive, long-term repopulating HSPCs and expand them in vitro for clinical purposes. Here we have tested the effect exerted by different culture media compositions on the ability of HSPCs to proliferate and undergo homology directed repair-mediated knock-in of a reporter gene, while preserving their stemness features during ex-vivo culture. We tested different combinations of compounds and demonstrated that by supplementing the culture media with inhibitors of histone deacetylases, and/or by fine-tuning its cytokine composition it is possible to achieve high levels of gene targeting in long-term repopulating HSPCs both in vitro and in vivo, with a beneficial balance between preservation of stemness and cell expansion, thus allowing to obtain a significant amount of edited, primitive HSPCs compared to established, state-of-the-art culture conditions. Overall, the implantation of this optimized ex vivo HSPC culture protocol will improve the efficacy, feasibility and applicability of gene editing and will likely provide one step further to unlock the full therapeutic potential of such powerful technology.

scholarly journals Mechanisms, Clinical Implications, and Treatment of Intradialytic Hypotension

2018 ◽  
Vol 13 (8) ◽  
pp. 1297-1303 ◽  
Author(s):  
Patrick B. Reeves ◽  
Finnian R. Mc Causland
Keyword(s):  
Adverse Outcomes ◽  
Maintenance Hemodialysis ◽  
Clinical Implications ◽  
Intradialytic Hypotension ◽  
Organ Perfusion ◽  
Compensatory Mechanisms ◽  
Weekly Basis ◽  
Related Factors ◽  
All Cause Mortality ◽  
Underlying Pathophysiology

Individuals with ESKD requiring maintenance hemodialysis face a unique hemodynamic challenge, typically on a thrice-weekly basis. In an effort to achieve some degree of euvolemia, ultrafiltration goals often involve removal of the equivalent of an entire plasma volume. Maintenance of adequate end-organ perfusion in this setting is dependent on the institution of a variety of complex compensatory mechanisms. Unfortunately, secondary to a myriad of patient- and dialysis-related factors, this compensation often falls short and results in intradialytic hypotension. Physicians and patients have developed a greater appreciation for the breadth of adverse outcomes associated with intradialytic hypotension, including higher cardiovascular and all-cause mortality. In this review, we summarize the evidence for adverse outcomes associated with intradialytic hypotension, explore the underlying pathophysiology, and use this as a basis to introduce potential strategies for its prevention and treatment.

scholarly journals Long Term Health Sequelae of COVID-19: A Review

2021 ◽  
Vol 08 (01) ◽  
pp. 9-18
Author(s):  
Naresh Kumar ◽  
Keyword(s):  
Distress Syndrome ◽  
Organ Damage ◽  
Acute Stage ◽  
Adverse Outcomes ◽  
World Health ◽  
Pulmonary Manifestations ◽  
History Of ◽  
Health Organization ◽  
Neurological System

The outbreak of Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by World Health Organization (WHO) on 11th March, 2020. COVID-19 infection predominantly manifests as pulmonary symptoms that may progress to acute respiratory distress syndrome. The data on extra-pulmonary manifestations of acute COVID-19 are available. Most patients who have COVID-19 recover well within months. Currently, more than 50 million people have recovered globally. Many reports of patients with persistent severe symptoms and significant end-organ damage after SARS-CoV-2 infection have also been observed. As COVID-19 is a relatively new disease, future sequelae aren’t well established. Major adverse outcomes were found to affect different body systems: respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy), and neurological system (sensory dysfunction and stroke). Mental health of COVID-19 patients were also found to be adversely affected. This review describes the effects of SARS-CoV-2 taking into account the previous experiences with SARS-CoV-2 and the Middle East Respiratory Syndrome (MERS) coronavirus that caused SARS in 2003 and MERS in 2012 respectively. This review aims to update on the long-term sequelae of SARS-CoV-2 infection and highlight the necessity for patient monitoring following the acute stage of infection with SARS-CoV-2 to provide ground for the prevention, diagnosis, and management of these potential long-term sequelae and to complete the natural history of COVID-19.

Antithrombotic Therapy for DVT/PE

1997 ◽  
Vol 17 (03) ◽  
pp. 161-162
Author(s):  
Thomas Hyers
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Cost Effective ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Term Therapy ◽  
Low Molecular Weight ◽  
Long Term Therapy

SummaryProblems with unfractionated heparin as an antithrombotic have led to the development of new therapeutic agents. Of these, low molecular weight heparin shows great promise and has led to out-patient therapy of DVT/PE in selected patients. Oral anticoagulants remain the choice for long-term therapy. More cost-effective ways to give oral anticoagulants are needed.

Antiplatelet Therapy in Acute Coronary Syndromes

2010 ◽  
Vol 6 (1) ◽  
pp. 58
Author(s):  
Sasha Koul ◽  
David Erlinge ◽  
◽  
Keyword(s):  
Platelet Function ◽  
Acute Coronary Syndromes ◽  
New Drugs ◽  
Antiplatelet Drugs ◽  
Bleeding Complications ◽  
Great Promise ◽  
Mortality Data ◽  
Poor Responders ◽  
Coronary Syndromes

Drugs inhibiting platelet function play a major role in the treatment of acute coronary syndromes (ACS). The first drug used, which is still considered the cornerstone of therapy today, is aspirin. Although very impressive in acutely decreasing rates of myocardial infarction as well as death, long-term data are scarce, despite our current recommendation for lifelong aspirin. The thienopyridines, most notably clopidogrel, are the next line of antiplatelet drugs. Well-documented data support the usage of clopidogrel for non-STEMI-ACS (NSTE-ACS). Although positive mortality data exist regarding clopidogrel and STEMI patients in a medically treated population, including thrombolysis, no larger amounts of randomised data exist in a primary PCI setting. Poor responders to aspirin and/or clopidogrel are a clinical problem, with these individuals constituting a higherrisk group for recurrent ischaemic events. Whereas very little can be done regarding aspirin resistance, clopidogrel resistance might be diminished by increasing the dosage or changing to more potent and newer-generation antiplatelet drugs. The role of glycoprotein IIb/IIIa inhibitors has diminished drastically and instead paved the way for thrombin antagonists (bivalirudin), which have fewer bleeding complications with resulting better long-term mortality. Novel adenosine diphosphate (ADP)-receptor blockers such as prasugrel and ticagrelor have shown increased efficacy over clopidogrel and hold great promise for the future. However, not all patients may benefit from these new drugs and economic constraints may also limit their use. Platelet function tests could possibly help in identifying risk groups in need of stronger platelet inhibition.

scholarly journals Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

2021 ◽  
Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Baseline Risk ◽  
Major Surgery ◽  
Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

scholarly journals Assessment of Exercise Intolerance in Patients with Pre-Dialysis CKD with Cardiopulmonary Function Testing: Translation to Everyday Practice

2021 ◽  
pp. 1-15
Author(s):  
Eva Pella ◽  
Afroditi Boutou ◽  
Marieta P. Theodorakopoulou ◽  
Pantelis Sarafidis
Keyword(s):  
Cardiovascular Risk ◽  
Risk Stratification ◽  
Cardiopulmonary Exercise Testing ◽  
Adverse Outcomes ◽  
Exercise Intolerance ◽  
Exercise Limitation ◽  
Integrative Evaluation ◽  
Prognostic Utility ◽  
Risk Potential

<b><i>Background:</i></b> Chronic kidney disease (CKD) is often characterized by increased prevalence of cardiovascular risk factors and increased incidence of cardiovascular events and death. Reduced cardiovascular reserve and exercise intolerance are common in patients with CKD and are associated with adverse outcomes. <b><i>Summary:</i></b> The gold standard for identifying exercise limitation is cardiopulmonary exercise testing (CPET). CPET provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic function during maximal or submaximal exercise. It is useful in clinical setting for differentiation of the causes of exercise intolerance, risk stratification, and assessment of response to relevant treatments. A number of recent studies have used CPET in patients with pre-dialysis CKD, aiming to assess the cardiovascular reserve of these individuals, as well as the effect of interventions such as exercise training programs on their functional capacity. This review provides an in-depth description of CPET methodology and an overview of studies that utilized CPET technology to assess cardiovascular reserve in patients with pre-dialysis CKD. <b><i>Key Messages:</i></b> CPET can delineate multisystem changes and offer comprehensive phenotyping of factors determining overall cardiovascular risk. Potential clinical applications of CPET in CKD patients range from objective diagnosis of exercise intolerance to preoperative and long-term risk stratification and providing intermediate endpoints for clinical trials. Future studies should delineate the association of CPET indexes, with cardiovascular and respiratory alterations and hard outcomes in CKD patients, to enhance its diagnostic and prognostic utility in this population.

Short- and long-term outcomes of preterm spontaneous twin anemia-polycythemia sequence

2020 ◽  
Vol 48 (4) ◽  
pp. 329-334
Author(s):  
Soo Jin Han ◽  
Seung Mi Lee ◽  
Sohee Oh ◽  
Subeen Hong ◽  
Jeong Won Oh ◽  
...  
Keyword(s):  
Cord Blood ◽  
Neonatal Morbidity ◽  
Adverse Outcomes ◽  
Control Group ◽  
Long Term Outcomes ◽  
Neurodevelopmental Outcomes ◽  
Monochorionic Twin ◽  
Increased Risk ◽  
Study Population

AbstractBackgroundIn monochorionic twin pregnancy, placental anastomosis and inter-twin blood transfusion can result in specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). It is well established that adverse outcomes are increased in TTTS, but reports on the neonatal and long-term outcomes of TAPS are lacking. The objective of this study was to evaluate the neonatal and neurodevelopmental outcomes in spontaneous TAPS.MethodsThe study population consisted of monochorionic twin pregnancies with preterm birth (24–37 weeks of gestation) between November 2003 and December 2016 and in which cord blood was taken at the time of delivery. According to the result of hemoglobin in cord blood, the study population was divided into two groups: a spontaneous TAPS group and a control group. Neonatal and neurodevelopmental outcomes were compared between the two groups.ResultsDuring the study period, 11 cases were diagnosed as spontaneous TAPS (6.4%). The TAPS group had lower gestational age at delivery and had a higher risk for cesarean delivery. However, neonates with TAPS were not at an increased risk for neonatal mortality and significant neonatal morbidity. In addition, the frequency of severe cerebral lesion during the neonatal period and the risk of cerebral palsy at 2 years of age were not different between the two groups.ConclusionThe spontaneous TAPS diagnosed by postnatal diagnostic criteria was not associated with the increased risk of adverse neonatal and neurodevelopmental outcomes. Further studies are needed to evaluate the morbidity of antenatally diagnosed TAPS.

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