Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
An 82-year-old man presenting with severe symptomatic tricuspid regurgitation (TR) and right heart failure (RHF).
Expert Opinion: The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC
The TricValve addresses the problem of severe ìncompetance of the tricuspid valve with a relatively simple procedure.
Instead of the challenge of replacing the defective valve, a catheter procedùre places valves at the two venous intake locations, the superior and ìnferior vena cava. A valve at the superior vena cava entrance to the right atrium occurs occasionally in nature, but is usually absent or fenestrated, covering the medial end if the crista supraventricularis.
A similar termed valve is occasionally found in nature on the inferior vena cava. These supernumerary valves can arrest back flow of pressure and volume from the right atrium to the upper and lower venous systems, and alleviate in particular congestion of the liver.
Normally the right atrial pressure is low, in which case this would offer no significant advantage for reproductive success natural selection to offset potential interference with blood flow into the right atrium that might promote thrombosis [Folia Morphology Morphology 66(4):303-6, MRuso].
However, in a setting of right heart failure, such as occurs from pulmonary hypertension, the tricuspid valve often becomes incompetent, and placement of the pair of vena cava valves can alleviate upstream consequences, albeit at the cost of risk of thrombosis and future impediment to other future procedures such as ablation of supraventricular arrhythmia.
The vena cava valves placed by catheter at the Cleveland Clinic helped an 80 year old man alleviate his pressing issue of hepatic congestion. Unlike a replacement tricuspid valve this procedure does not alleviate high pressures dilatìng the right atrium. Instead, it can worsen that problem.
The CLASP II TR trial is investigating the Edwards PASCAL transcatheter repair system [CLASP II TR, Edwards Lifesciences Corp, NIH NCT 0497145]
Survival data for surgìcal tricuspid valve replacements reported 37+-10 percent ten year survival, with average all cause survival of just 8.5 years [Z HIscan, Euro J CT Surgery 32(2) Aug 2007]. None-the‐less, comparison of patients with vs without intervention for incompetance of the trìcuspid valve favored mechanical intervention [G Dreyfus Ann Thorac Surg 49:706-11,1990, D Adams, JACC 65:1931-8, 2015]. Time will tell which interventìon will prevail, and when these catheter alternatives to open chest surgery should be deployed.
Rishi Puri, MD, PhD, an interventional cardiologist with Cleveland Clinic, and Samir Kapadia, MD, chair of cardiovascular medicine at Cleveland Clinic, performed the procedure. Puri has years of experience with the TricValve system, participating in a thorough analysis of its safety and effectiveness in 2021.
The TricValve system features two biological valves designed to be implanted via femoral vein access into the patient’s superior vena cava and inferior vena cava. This allows a therapy without impacting the patient’s native tricuspid valve. It is available in multiple sizes, allowing cardiologists to choose the best option for each individual patient.
Cleveland Clinic’s statement detailing the successful procedure notes that patients with severe TR and RHF have typically had limited treatment options. Tricuspid valve surgery is associated with significant risks, for instance, and prescribing diuretics is problematic when the patient also presents with kidney problems.
“TricValve can potentially provide an effective and low-risk solution for many patients who currently have no treatment options,” Puri said, adding that the workflow is quite similar to transcatheter aortic valve replacement.
The TricValve Transcatheter Bicaval Valves System was developed by P+F Products + Features GmbH, a healthcare technology company based out of Vienna, Austria. The solution was granted the FDA’s Breakthrough Device designation in December 2020, but it has still not gained full FDA approval.
This procedure was completed under a compassionate-use clearance from the FDA.
Parasym™ neuromodulation device reveals promising developments in the treatment of heart failure patients with preserved ejection fraction: Clinical Trial Results
Reporter and Curator: Aviva Lev-Ari, PhD, RN
Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Clinical Trial
A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction. Low‐level transcutaneous vagus nerve stimulation suppresses inflammation in humans. We conducted a sham‐controlled, double‐blind, randomized clinical trial to examine the effect of chronic low‐level transcutaneous vagus nerve stimulation on cardiac function, exercise capacity, and inflammation in patients with heart failure with preserved ejection fraction.
Methods and Results
Patients with heart failure with preserved ejection fraction and at least 2 additional comorbidities (obesity, diabetes, hypertension, or age ≥65 years) were randomized to either active (tragus) or sham (earlobe) low‐level transcutaneous vagus nerve stimulation (20 Hz, 1 mA below discomfort threshold), for 1 hour daily for 3 months. Echocardiography, 6‐minute walk test, quality of life, and serum cytokines were assessed at baseline and 3 months. Fifty‐two patients (mean age 70.4±9.2 years; 70% female) were included (active, n=26; sham, n=26). Baseline characteristics were balanced between the 2 arms. Adherence to the protocol of daily stimulation was >90% in both arms (P>0.05). While the early mitral inflow Doppler velocity to the early diastolic mitral annulus velocity ratio did not differ between groups, global longitudinal strain and tumor necrosis factor‐α levels at 3 months were significantly improved in the active compared with the sham arm (−18.6%±2.5% versus −16.0%±2.4%, P=0.002; 8.9±2.8 pg/mL versus 11.3±2.9 pg/mL, P=0.007, respectively). The reduction in tumor necrosis factor‐α levels correlated with global longitudinal strain improvement (r=−0.73, P=0.001). Quality of life was better in the active arm. No device‐related side effects were observed.
Conclusions
Neuromodulation with low‐level transcutaneous vagus nerve stimulation over 3 months resulted in a significant improvement in global longitudinal strain, inflammatory cytokines, and quality of life in patients with heart failure with preserved ejection fraction.
Press Release Announcement by Parasym™ is a neurotechnology company dedicated to shaping the future of bioelectric medicine. Founded in 2015 by Sophie and Nathan Dundovic, is focused on providing innovative neuromodulation products that restore health. The company has over 60 clinical partnerships across 4 continents, and over 1,000,000 treatment sessions completed. For more information about Parasym™’s latest products, visit nurosym.com
Parasym™ is the only company to have developed a device that utilises advances in electroceutical technology to provide ground-breaking non-invasive treatment for numerous health and wellness conditions ranging from mental to physical health including heart failure, without the need for heart failure medication. For further information about Parasym™ visit parasym.co.
The neuromodulation device is non-invasive, patients are able to use it in addition to medication should they want to. Electroceuticals are set to revolutionise the treatment paradigm in heart failure, especially neuromodulation with its capacity to provide highly targeted treatment without drug interaction or side effects.
Clinical trial results
The study revealed significant improvements in levels of proinflammatory cytokines Interleukin-8 and Tumour Necrosis Factor alpha, indicating that the treatment had a significant anti-inflammatory effect, as well as in global longitudinal strain, a core indicator of cardiac mechanics.
Dr Stavros Stavrakis MD, PhD, Associate Professor at University of Oklahoma College of Medicine commented: “We conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low-level transcutaneous vagus nerve stimulation on cardiac function, exercise capacity, and inflammation in a subgroup of patients with heart failure with preserved ejection fraction with a predominantly inflammatory-metabolic phenotype. In this patient population, neuromodulation with low-level transcutaneous vagus nerve stimulation over three months resulted in a significant improvement in global longitudinal strain, inflammatory cytokines, and quality of life. Our results support the emerging paradigm of noninvasive neuromodulation to treat selected patients with heart failure with preserved ejection fraction and provide the basis for further randomized trials.”
Parasym™️ is committed to supporting groundbreaking cardiac research and we are working to bring non-invasive electroceutical treatments to patients suffering from heart failure.
“The results published in the Journal of the American Heart Association highlight the brilliant work done by researchers at the University of Oklahoma and show the incredible potential that Parasym’s neuromodulatory technology can have in a condition where there is an urgent unmet clinical need for new treatment options. We are incredibly proud of the trial results and hope to continue to demonstrate the positive impact of neuromodulation in healthcare.”
SOURCE
From: Sofia Leadbetter <sofia@lem-uhn.com> Date: Tuesday, February 22, 2022 at 9:56 AM To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu> Subject: Re: A groundbreaking clinical trial using Parasym™ neuromodulation device reveals promising developments in the treatment of heart failure
Other related articles published in this Open Access Online Scientific Journal includes the following:
I. A related topic is Renal denervation for Hypertension control by a medical device
Single-Author Reporting on MedTech and Cardiac Medical Devices by
Experimental Therapy (Left inter-atrial shunt implant device) for Heart Failure: Expert Opinion on a Preliminary Study on Heart Failure with preserved Ejection Fraction
This book is a comprehensive review of Nitric Oxide, its discovery, function, and related opportunities for Targeted Therapy written by Experts, Authors, Writers: PhDs, MDs, MD/PhDs, PharmDs. Nitric oxide plays a wide variety of roles in cardiovascular system and acts as a central point for signal transduction pathway in endothelium. NITRIC OXIDE modulates vascular tone, fibrinolysis, blood pressure and proliferation of vascular smooth muscle cells. In the cardiovascular system disruption of NITRIC OXIDE pathways or alterations in NITRIC OXIDE production can result in predisposition to hypertension, hypercholesterolemia, diabetes mellitus, atherosclerosis and thrombosis. The essential role of NITRIC OXIDE is seen widely in organ function and in disease development. The role of NITRIC OXIDE covers the cardiovascular system, the acuity of sepsis and septic shock, gastrointestinal disease, renal disease, and neurological disorders. The final chapter is the essential role of NITRIC OXIDE in carcinogenesis. Therapeutic Targets to Clinical Applications: Pharmaco-therapy was developed and it represents methods to induce the production of Nitric Oxide and its enzymes for novel combination drug therapies.
This e-Book is a comprehensive review of recent Original Research on Cardiovascular Diseases: Causes, Risks and Management and related opportunities for Targeted Therapy written by Experts, Authors and Writers. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012. Topics covered in greater details include: •Alternative solutions in Treatment of Heart Failure (HF), medical devices, biomarkers and agent efficacy are handled all in one chapter. •PCI for valves vs Open heart Valve replacement •PDA and Complications of Surgery — only curation could create the picture of this unique combination of debate, as exemplified of Endarterectomy (CEA) vs Stenting the Carotid Artery (CAS), ischemic leg, renal artery stenosis.
This e-Book is a comprehensive review of recent Original Research on Cardiovascular Diseases: Causes, Risks and Management and related opportunities for Targeted Therapy written by Experts, Authors and Writers. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012. This e-Book includes a thorough evaluation of a rich source of research literature on the genomic influences, which may have variable strength in the biological causation of atherosclerosis, microvascular disease, plaque formation, not necessarily having expressing, except in a multivariable context that includes the environment, dietary factors, level of emotional stress, sleep habits, and the daily activities of living for affected individuals. The potential of genomics is carried in the DNA, copied to RNA, and this is most well studied in the micro RNAs (miRNA). The miRNA has been explored for the appearance in the circulation of specific miRNAs that might be associated with myocyte or endothelial cell injury, and they are also being used as targets for therapeutics by the creation of silencing RNAs (siRNA).
This e-Book is a comprehensive review of recent Original Research on Cardiovascular Diseases: Causes, Risks and Management and related opportunities for Targeted Therapy written by Experts, Authors and Writers. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012. Part 1 is concerned with Posttranslational Modification of Proteins, vital for understanding cellular regulation and dysregulation. Part 2 is concerned with Translational Medical Therapeutics, the efficacy of medical and surgical decisions based on bringing the knowledge gained from the laboratory, and from clinical trials into the realm opf best practice. The time for this to occur in practice in the past has been through roughly a generation of physicians. That was in part related to the busy workload of physicians, and inability to easily access specialty literature as the volume and complexity increased. This had an effect of making access of a family to a primary care provider through a lifetime less likely than the period post WWII into the 1980s.
Pharmacologic therapy represents the dominant strategy for management of cardiovascular disease and consequences, deferring, complementing and often supplanting structural and functional interventions. The general strategy of medical management is to identify the biochemicals that control cardiovascular functions and responses, identify the consequences of push and pull (stimulation, potentiation, inhibition, blockade, counteractivity), check benefits and harm, systematically document the impact, both in population studies and in individuals, make wise choices, and optimize dosing. Medications mimic or modify natural biologic activities. Therefore genomics (the study of gene products, especially, messengers and receptors) and the cascade of signaling pathways that modulate responses identifies the myriad but theoretically finite possibilities for chemical intervention. Often there are many pathways that affect or are affected by cardiovascular disease, and multiple ways to promote desirable changes. Elucidation of the biochemical signal changes that correspond to or respond to cardiovascular disease conditions and treatments provides both biomarkers of patient health status and targets for therapy. The process of homeostasis resists change, including resisting desirable changes that aim to correct maladaptive biology. Thus medication to block an excess in heart rate and blood pressure, for example, leads to upregulation in the number and sensitivity of blocked receptors as well changes in activity of sibling pathways, which mitigate the impact of the blocking medication and promote rebound worsening of the primary concern if the medication gets interrupted. These issues influence combination therapy choices as well as concern about compliance with prescriptions. Therefore this guided tour of curated data relating to medical management of cardiovascular diseases draws from the human genome project to identify treatment opportunities, pathophysiology to understand the impact of disease and maladaptive responses, clinical disease and pharmaceutical classifications, and clinical trial results to clarify expected outcomes. Curation also addresses context, insight and opportunity. Review of all of the above by teams of experts leads to formulation of guidelines, but each patient is a unique individual for whom customized optimization offers further benefits. Optimal care requires understanding of all of the above to guide and optimize the offering and patient education for wise choices promoting optimal quality and quantity of life despite the presence of cardiovascular disease. Current health care priorities, current cardiovascular medication classification and offerings, and in depth review of the achievements and limitations of current and anticipated future pharmaceutical therapies for cardiovascular disease are. The current priorities adapt to cost benefit analysis of prevalent cardiovascular disorders, as limited resources are arguably best directed to where they will do the most good. The scope of that concern includes prevention as well as curtailment of severity of impairment, by improving out patient management, aiming at alleviated suffering and achieve sufficient quality of life to avoid expensive hospitalizations, interference with productivity, and shortened lifespan. Major categories of cardiovascular disease are reviewed in separate chapters, based on distinct pathways and therapeutic considerations. The closing chapter addresses adverse effects of therapy. In Part Two we focus on biomarkers – indicators of disease status. Chapter 15 presented recent new examples, such as BNP and high-sensitivity Troponin. Ch.16 addressed how the completion of the mapping of the human genome paves the way for identifying many more biomarkers. Ch.17 reviewed biomarker utility in various disease conditions. Ch.18 reviewed biomarker utility in acute disorders. Ch.19 on cholesterol, lipids, diet and Ch.20 on Inflammation.
In Cardiology, “Interventional” is reserved for procedures that directly produce physical changes. Surgical interventions for cardiovascular diseases include heart or heart and lung transplant, implantation of cardiac assist devices, shock devices and pacemakers, bypass grafts for coronary or other arteries, valve repairs or replacement, removal of plaque (endarterectomy), removal of tumors, and repair or palliation of injuries or of congenital anomalies. All of these interventions are continually studied and improved, with a major effort at minimizing the risk, reducing recovery time and reducing the size of entry scar, for example by use of video scopes instead of direct visualization, and mechanical devices and robotics instead of direct manual access. Interventional Cardiology refers to an often competing non-surgical approach in which access is limited to entry by vein or artery (catheterization). The two teams have joined forces to achieve a major success in replacing aortic valves by femoral artery access without opening the chest at all (TAVR), with on-going progress towards a similar approach to mitral valve replacement. This book addresses disease prevalence, personalized patient and doctor experiences with Cardiac Surgery, the role of transfusion, status of the MedTech market, and a review of major accomplishments from pathology, anesthesiology, radiology, cardiology and surgery. The contributions of specific groups, such as the Texas Heart Institute, the Dalio Institute at New York Presbyterian/Weill Cornell, the Cleveland Clinic, and the Scripps Institute are reviewed. Individual contributions from Eric Topol, Arthur Moss, Paul Zoll, Tim Wu, and Earl E. Bakken (Medtronic co-founder) are included. Discoveries in relevant biology, including ATP (the metabolic paycheck) and plasma metabolomics, and novel technologies such as tethered-liquid perfluorocabon surface biocoating to prevent clotting. Additional curations present views of cardiothoracic surgeons, vascular surgeons and of Catheterization lab interventionists. Business aspects are addressed by review of costs, prevalence, payment methods, prevention impact and business models. Decision support tools are also reviewed, and changes in guidelines. Voices of three Open Heart Surgery Survivors are included. Chapters 4-6 addressed clinical trial data in coronary disease, biomarkers of cardiovascular disorders, coagulation including top roles of nitric oxide, C-reative protein, protein C, aprotinin and thrombin. Chapters 7-8 covered amyloidosis, atherosclerosis, valve disease, flow reserve, atrial fibrillation and roles for advanced imaging. Chapters 9-10 covered unstable angina, transplants, and ventricular assist devices. Chapters 11-14 span interventions on the aorta, peripheral arteries, and coronary arteries, valve surgery and percutaneous valve repair or replacement, plus the growing role of prosthetics and repair by stem cells and tissue engineering. As catheter techniques evolved to compete with bypass surgery they progressed from balloon cracking of obstructive lesions (POBA=plain old balloon angioplasty) to placement of stents (wire fences). Surgeons sometimes use in-stent valves, and now devices analogous to in-stent valves can be placed by catheter for valve replacement in patients with too much co-morbidity to go through heart surgery. Aortic valve replacement by stent (TAVR) has had sufficient success to be considered for all patients who have sufficient impairment to merit intervention. The diameter is large, so a vascular surgeon participates in the arterial access and repair of the access site. Minimally invasive repair of abdominal aorta aneurysm: atherosclerosis offers potentially somewhat protective stiffening of the arterial wall, it can promote clots, athero-emboli, and failure of the remodeling can lead to an outward ballooning, or aneurysm, that promotes both clot formation and wall or lining tears or rupture, cause of sudden death.
New avenues for research in membrane biology reveals the mobility of protein at work
Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc
Membrane proteins(MPs) are proteins that exist in the plasma membrane and conduct a variety of biological functions such as ion transport, substrate transport, and signal transduction. MPs undergo function-related conformational changes on time intervals spanning from nanoseconds to seconds. Many MP structures have been solved thanks to recent developments in structural biology, particularly in single-particle cryo-Electron Microscopy (cryo-EM). Obtaining time-resolved dynamic information on MPs in their membrane surroundings, on the other hand, remains a significant difficulty.
OmpG (Open state) in a fully hydrated dimyristoylphosphatidylcholine (DMPC) bilayer. The protein is shown in light green cartoon. Lipids units are depicted in yellow, while their phosphate and choline groups are illustrated as orange and green van der Waals spheres, respectively. Potassium and chloride counterions are shown in green and purple, respectively. A continuous and semi-transparent cyan representation is used for water. https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-021-24660-1/MediaObjects/41467_2021_24660_MOESM1_ESM.pdf
Weill Cornell Medicine (WCM) researchers have found that they can record high-speed protein movements while linking them to function. The accomplishment should allow scientists to examine proteins in more depth than ever before, and in theory, it should allow for the development of drugs that work better by hitting their protein targets much more effectively.
The researchers utilized High-Speed Atomic Force Microscopy (HS-AFM) to record the rapid motions of a channel protein and published in a report in Nature Communications on July 16. Such proteins generally create channel or tube-like structures in cell membranes, which open to allow molecules to flow under particular conditions. The researchers were able to record the channel protein’s rapid openings and closings with the same temporal resolution as single channel recordings, a typical technique for recording the intermittent passage of charged molecules through the channel.
Senior author Simon Scheuring, professor of physiology and biophysics in anesthesiology at WCM, said,
There has been a significant need for a tool like this that achieves such a high bandwidth that it can ‘see’ the structural variations of molecules as they work.
Researchers can now produce incredibly detailed photographs of molecules using techniques like X-ray crystallography and electron microscopy, showing their structures down to the atomic scale. The average or dominant structural positionings, or conformations, of the molecules, are depicted in these “images,” which are often calculated from thousands of individual photos. In that way, they’re similar to the long-exposure still photos from the dawn of photography.
Many molecules, on the other hand, are flexible and always-moving machinery rather than fixed structures. Scientists need to generate videos, not still photos, to reveal how such molecules move as they work, to see how their motion translates to function to catch their critical functional conformations, which may only exist for a brief moment. Current techniques for dynamic structural imaging, on the other hand, have several drawbacks, one of which being the requirement for fluorescent tags to be inserted on the molecules being photographed in many cases.
Scheuring and his lab were early adopters of the tag-free HS-AFM approach for studying molecular dynamics. The technology, which can photograph molecules in a liquid solution similar to a genuine cellular environment, employs an extremely sensitive probe, similar to a record player’s stylus, to feel its way over a molecule and therefore build up a picture of its structure. Standard HS-AFM isn’t quick enough to capture the high-speed dynamics of many proteins, but Scheuring and colleagues have developed a modified version, HS-AFM height spectroscopy(HS-AFM-HS), that works much faster by collecting dynamic changes in only one dimension: height.
The researchers used HS-AFM-HS to record the opening and closing of a relatively simple channel protein, OmpG, found in bacteria and widely studied as a model channel protein in the new study, led by the first author Raghavendar Reddy Sanganna Gari, a postdoctoral research associate in Scheuring’s laboratory. They were able to monitor OmpG gating at an effective rate of roughly 20,000 data points per second, seeing how it transitioned from open to closed states or vice versa as the acidity of the surrounding fluid varied.
More significantly, they were able to correlate structural dynamics with functional dynamics in a membrane protein of this size for the first time in a partnership with Crina Nimigean, professor of physiology and biophysics in anesthesiology, and her group at WCM.
The demonstration opens the door for a wider application of this method in basic biology and drug development.
Sanganna Gari stated,
We’re now in an exciting period of HS-AFM technology, for example using this technique to study how some drugs modulate the structural dynamics of the channel proteins they target.
Main Source
Technique reveals proteins moving as they work. By Jim Schnabel in Cornell Chronicle, August 16, 2021.
Patients with type 2 diabetes may soon receive artificial pancreas and a smartphone app assistance
Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc
In a brief, randomized crossover investigation, adults with type 2 diabetes and end-stage renal disease who needed dialysis benefited from an artificial pancreas. Tests conducted by the University of Cambridge and Inselspital, University Hospital of Bern, Switzerland, reveal that now the device can help patients safely and effectively monitor their blood sugar levels and reduce the risk of low blood sugar levels.
Diabetes is the most prevalent cause of kidney failure, accounting for just under one-third (30%) of all cases. As the number of people living with type 2 diabetes rises, so does the number of people who require dialysis or a kidney transplant. Kidney failure raises the risk of hypoglycemia and hyperglycemia, or unusually low or high blood sugar levels, which can lead to problems ranging from dizziness to falls and even coma.
Diabetes management in adults with renal failure is difficult for both the patients and the healthcare practitioners. Many components of their therapy, including blood sugar level targets and medications, are poorly understood. Because most oral diabetes drugs are not indicated for these patients, insulin injections are the most often utilized diabetic therapy-yet establishing optimum insulin dose regimes is difficult.
Patients living with type 2 diabetes and kidney failure are a particularly vulnerable group and managing their condition-trying to prevent potentially dangerous highs or lows of blood sugar levels – can be a challenge. There’s a real unmet need for new approaches to help them manage their condition safely and effectively.
The artificial pancreas is a compact, portable medical device that uses digital technology to automate insulin delivery to perform the role of a healthy pancreas in managing blood glucose levels. The system is worn on the outside of the body and consists of three functional components:
a glucose sensor
a computer algorithm for calculating the insulin dose
an insulin pump
The artificial pancreas directed insulin delivery on a Dana Diabecare RS pump using a Dexcom G6 transmitter linked to the Cambridge adaptive model predictive control algorithm, automatically administering faster-acting insulin aspart (Fiasp). The CamDiab CamAPS HX closed-loop app on an unlocked Android phone was used to manage the closed loop system, with a goal glucose of 126 mg/dL. The program calculated an insulin infusion rate based on the data from the G6 sensor every 8 to 12 minutes, which was then wirelessly routed to the insulin pump, with data automatically uploaded to the Diasend/Glooko data management platform.
The Case Study
Between October 2019 and November 2020, the team recruited 26 dialysis patients. Thirteen patients were randomly assigned to get the artificial pancreas first, followed by 13 patients who received normal insulin therapy initially. The researchers compared how long patients spent as outpatients in the target blood sugar range (5.6 to 10.0mmol/L) throughout a 20-day period.
Patients who used the artificial pancreas spent 53 % in the target range on average, compared to 38% who utilized the control treatment. When compared to the control therapy, this translated to approximately 3.5 more hours per day spent in the target range.
The artificial pancreas resulted in reduced mean blood sugar levels (10.1 vs. 11.6 mmol/L). The artificial pancreas cut the amount of time patients spent with potentially dangerously low blood sugar levels, known as ‘hypos.’
The artificial pancreas’ efficacy improved significantly over the research period as the algorithm evolved, and the time spent in the target blood sugar range climbed from 36% on day one to over 60% by the twentieth day. This conclusion emphasizes the need of employing an adaptive algorithm that can adapt to an individual’s fluctuating insulin requirements over time.
When asked if they would recommend the artificial pancreas to others, everyone who responded indicated they would. Nine out of ten (92%) said they spent less time controlling their diabetes with the artificial pancreas than they did during the control period, and a comparable amount (87%) said they were less concerned about their blood sugar levels when using it.
Other advantages of the artificial pancreas mentioned by study participants included fewer finger-prick blood sugar tests, less time spent managing their diabetes, resulting in more personal time and independence, and increased peace of mind and reassurance. One disadvantage was the pain of wearing the insulin pump and carrying the smartphone.
Not only did the artificial pancreas increase the amount of time patients spent within the target range for the blood sugar levels, but it also gave the users peace of mind. They were able to spend less time having to focus on managing their condition and worrying about the blood sugar levels, and more time getting on with their lives.
The team is currently testing the artificial pancreas in outpatient settings in persons with type 2 diabetes who do not require dialysis, as well as in difficult medical scenarios such as perioperative care.
“The artificial pancreas has the potential to become a fundamental part of integrated personalized care for people with complicated medical needs,” said Dr Lia Bally, who co-led the study in Bern.
The authors stated that the study’s shortcomings included a small sample size due to “Brexit-related study funding concerns and the COVID-19 epidemic.”
Boughton concluded:
We would like other clinicians to be aware that automated insulin delivery systems may be a safe and effective treatment option for people with type 2 diabetes and kidney failure in the future.
A highly effective platforms for the ex utero culture of post-implantation mouse embryos have been developed in the present study by scientists of the Weizmann Institute of Science in Israel. The study was published in the journal Nature. They have grown more than 1,000 embryos in this way. This study enables the appropriate development of embryos from before gastrulation (embryonic day (E) 5.5) until the hindlimb formation stage (E11). Late gastrulating embryos (E7.5) are grown in three-dimensional rotating bottles, whereas extended culture from pre-gastrulation stages (E5.5 or E6.5) requires a combination of static and rotating bottle culture platforms.
At Day 11 of development more than halfway through a mouse pregnancy the researchers compared them to those developing in the uteruses of living mice and were found to be identical. Histological, molecular and single-cell RNA sequencing analyses confirm that the ex utero cultured embryos recapitulate in utero development precisely. The mouse embryos looked perfectly normal. All their organs developed as expected, along with their limbs and circulatory and nervous systems. Their tiny hearts were beating at a normal 170 beats per minute. But, the lab-grown embryos becomes too large to survive without a blood supply. They had a placenta and a yolk sack, but the nutrient solution that fed them through diffusion was no longer sufficient. So, a suitable mechanism for blood supply is required to be developed.
Till date the only way to study the development of tissues and organs is to turn to species like worms, frogs and flies that do not need a uterus, or to remove embryos from the uteruses of experimental animals at varying times, providing glimpses of development more like in snapshots than in live videos. This research will help scientists understand how mammals develop and how gene mutations, nutrients and environmental conditions may affect the fetus. This will allow researchers to mechanistically interrogate post-implantation morphogenesis and artificial embryogenesis in mammals. In the future it may be possible to develop a human embryo from fertilization to birth entirely outside the uterus. But the work may one day raise profound questions about whether other animals, even humans, should or could be cultured outside a living womb.
Left Ventricular Volume Reduction and Reshaping as a Treatment Option for Heart Failure
Reporter: Aviva Lev-Ari, PhD, RN
Left Ventricular Remodeling and Its Reversal
When the myocardium is subjected to abnormal mechanical and neurohormonal stresses, left ventricular remodeling ensues with a progression of structural, cellular, molecular, metabolic, and functional changes.
In chronic heart failure with reduced ejection fraction, this remodeling affects the left ventricle with consequences that include ventricular dilation, transition of the chamber shape from elliptical to spherical, and the shifting of papillary muscles and mitral valve apparatus into abnormal positions. Ironically, while remodeling is an outgrowth of the initial hemodynamic and metabolic insults that lead to heart failure, it is also self-propagating, contributing to the progressive loss of ventricular function over time.
In the July 20 online issue of Structural Heart, heart failure specialists at Columbia University Vagelos College of Physicians and Surgeons present a comprehensive review of treatment options that focus on restoring the normal ventricular size and preventing the remodeling process from continuing. But can preventing or limiting left ventricular remodeling following an insult or reversing it once it is present reduce cardiovascular morbidity?
Their article provides insight into this question with a view toward better understanding the impact of remodeling on ventricular dysfunction and an in-depth look at therapeutic approaches, including those that are well-established, several that are currently under investigation, as well as those that have been invalidated and no longer used. The authors focus on two fundamental therapeutic approaches – those that rely primarily on
biological mechanisms to induce responses in the myocardium and improve myocardial function, and
physical mechanisms, involving procedures where a portion of the heart is either removed or excluded and devices to reduce myocardial wall stress through ventricular constraint or reshaping.
Bioresorbable Stent Clinical Trials with New Esprit Below-the-knee Scaffold
Reporter: Irina Robu, PhD
Abbott announced on September 3, 2020, the beginning of the LIFE-BTK clinical trial to evaluate effectiveness and safety of the Esprit BTK Everolimus Eluting Resorbable Scaffold System. The Esprit BTK System consists of a thin strutted scaffold made of poly-L-lactide, a semi-crystalline bioresorbable polymer engineered to resist vessel recoil and provide a platform for drug delivery. The scaffold is coated with poly-D, L-lactide (PDLLA) and the cytostatic drug, everolimus.
This trial is the first Investigational Device Exemption in the US to assess a fully bioresorbable stent to treat blocked arteries below the knees, also known as critical limb ischemia in people battling advanced stages of peripheral artery disease. For people with CLI, blocked vessels weaken blood flow to the lower extremities, which can lead to severe pain, wounds, and in severe cases, limb amputation.
At this time, the standard of care for patients battling critical limb ischemia is balloon angioplasty, which depend on on a small balloon delivered via a catheter to the blockage to compress it against the arterial wall, opening the vessel and restoring blood flow. Yet, blockages treated only with balloon angioplasty have poor short- and long-term results, and in many cases the vessels become blocked again, lacking additional treatment.
Patients treated with balloon angioplasty often require several procedures on treated arteries, and a drug eluting resorbable device is if at all possible suited to provide mechanical support, decrease the chance of the vessel re-narrowing and then slowly disappear over time. At this time, there are no drug eluding stents, drug coated balloons or bare metal stents approved for use below the knee. Since, there is a limited number of options for stents below the knee, the FDA has granted Esprit BTK breakthrough device designation, which simplifies review and pre-market approval timelines.
According to Abbott, Espirit BTK System is not a permanent implant, but it does provide support to an artery right after a balloon angioplasty, stopping the vessel from reclosing. As soon as it is implanted, the scaffold distributes a drug over a few months that encourages healing and keeps the artery open. The scaffold is naturally resorbed into the body over time, like dissolving sutures, and eventually leaves only a healed artery behind.
The LIFE-BTK trial is the first Investigational Device Exemption trial in the U.S. to evaluate a fully dissoluble device to treat critical limb ischemia in people battling advanced stages of peripheral artery disease (PAD). The trial will be run by principal investigators Brian DeRubertis, M.D. (vascular surgeon, UCLA), Sahil Parikh M.D., (interventional cardiologist, New York-Presbyterian/Columbia University Irving Medical Center.
Targeting Atherosclerotic Plaques with Stents made of Drug-eluting Biomaterials
Reporter: Daniel Menzin, BSc BioMedical Engineering, expected, May 2021, Research Assistant 4, Core Applications Developer and Acting CTO
Atherosclerosis is a chronic cardiovascular disease with a multitude of different implications. A coronary artery plaque may lead to congestive heart failure while an aortic plaque may cause angina. Both can quite possibly lead to a heart attack unless properly managed. One way to manage this condition is through the use of stents made of a mesh that is expanded following placement into the diseased vessel.
Unfortunately, stents are oftentimes initially effective but eventually restenosis occurs. Restenosis is a condition in which the affected vessel becomes blocked again. Cholesterol-rich blood vessel environments oftentimes lead to an irritation that results in white blood cells aggregating in the area and releasing proinflammatory chemokines and cytokines, which cause fibrosis. To make matters worse, the cholesterol plaques undergo compression against the vessel wall which causes vessel injury and further inflammation. This leads to thrombus formation and may potentiate neointimal hyperplasia, an abnormal proliferation and migration of smooth muscle cells in the tunica intima. Neointimal hyperplasia plays a major role in restenosis.
Recent research has found that interfacing drug eluting biomaterials with stents may help prevent restenosis. One study showed that rapamycin delivered with acid labile and ROS-sensitive forms of Beta-cyclodextrin produced promising results when treating atherosclerosis in rat models (Dou, et al). In this promising new paradigm of treatment, non-proinflammatory biomaterials are interfaced with stents. Once inflammation appears the biomaterial will begin to degrade, slowly releasing the drug which suppresses the underlying immune reaction and the resulting inflammation.
SOURCE
Dou Y;Chen Y;Zhang X;Xu X;Chen Y;Guo J;Zhang D;Wang R;Li X;Zhang J; “Non-Proinflammatory and Responsive Nanoplatforms for Targeted Treatment of Atherosclerosis.” Biomaterials, U.S. National Library of Medicine, 29 July 2017, pubmed.ncbi.nlm.nih.gov/28778000/.
Other related articles published in this Open Access Online Scientific Journal include:
First Surgical Robot Making Surgeon’s Life More Efficient
Reporter : Irina Robu, PhD
A team of microsurgeons and engineers, developed a high-precision robotic assistant called MUSA which is clinically and commercially available. The high precision robotic assistant is compatible with current operating techniques, workflow, instruments and other or instrument. Microsure is a medical device company in The Netherlands founded by Eindhoven University of Technology and Maastricht University Medical Center in 2016. Microsure’s focus is to improve patients’ quality of life through developing robot systems for microsurgery.
The Microsure’s MUSA enhances surgical performance by stabilizing and scaling down the surgeon’s movements during complex microsurgical procedures on sub-millimeter scale. The surgical robot, allows lymphatic surgery on lymph vessels smaller than 0.3 mm in diameter. Microsure received the ISO 13485 certificate which assures that Microsure is adhering to the highest standards in quality management and regulatory compliance procedures to develop, manufacture, and test its products and services.
MUSA provides superhuman precision for microsurgeons, enabling new interventions that are currently impossible to perform by hand.
Theranica, Israeli startup is developing a non-invasive medical device that treats migraine pain through smartphone-controlled electric pulses unlike existing pharmaceutical solutions like triptans and ergotamine. The company recently received FDA De-novo clearance on Nerivio Migra, a class II medical device to treat acute migraine pain.
The non-invasive medical device, Nerivio Migra contains a bioelectric patch which is placed on the upper arm and a linked smartphone app which controls the electrical impulses and records data. The device’s electric pulses excite C-fiber nerves, generating an analgesic mechanism in the brain that lightens migraine pain.
In order to diminish the overuse of painkillers, the company developed the non-invasive device and tested it among acute migraine patients both two and 48 hours after treatment. Side effects from the device were mild and resolved within 24 hours.
Theranica’s product is lower in price than the existing alternatives and it is using existing smartphone technology. Their initial focus is on marketing to headache clinics as a start. And hoping to expand the indications for its device to the pediatric migraine population and finally use its platform to treat other idiopathic pain conditions like cluster headaches.
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