At present, mitral heart valve failure is treated through invasive surgery or via a transcatheter procedure called Transcatheter Edge-to-Edge Repair (TEER). However, this procedure is difficult to perform, potentially resulting in suboptimal outcomes in challenging cases and if done by inexperienced clinicians.
To address this, Moray Medical, a company based in Mountain View, California, has developed a robotic catheter and associated technology, including augmented reality and a 3D digital interface, designed to make the job easier. In fact, the company claims that using its technology to deliver cardiac therapies can be as simple as moving a cursor on a computer screen.
The company hopes that its offerings will enable effective mitral heart valve repair outside of specialized centers of excellence, thereby expanding the number of patients who can avail of the treatment. Moray Medical was recently shortlisted for the MedTech Innovator, 2020 Grand Prize for its device.
Medgadget had the opportunity to talk to Mark Barrish, Co-Founder and CEO of Moray Medical about their technology, but first here's a quick preview of how it works:
Conn Hastings, Medgadget: Please give us an overview of mitral heart valve failure. What is it, and who does it affect?
Mark Barrish, Moray Medical: The mitral valve is a high-pressure one-way valve between two of the chambers of the heart that allows blood from the lungs to be pumped in one direction and prevents reverse flow. Mitral valve failure (also called mitral incompetence or mitral regurgitation (MR)) is a failure of the mitral valve to close tightly when it should. When the heart squeezes to pump blood to the other muscles and organs, this failure results in blood flowing back toward the lungs. While many patients with mild MR remain asymptomatic for years, those with significant mitral regurgitation typically feel tired and out of breath, and the condition often progresses until it becomes debilitating and for far too many, fatal.
Two million people develop moderate to severe mitral regurgitation (MR class 3+) in the US each year. MR can occur at any age and acute MR can strike suddenly, but most patients develop symptomatic MR from other cardiovascular issues as they age. For example, if the heart chambers expand over time the valve leaflets—the tissue structures which engage against each other every heartbeat to prevent blood flowing backward—can gradually separate. In other patients the disease originates within the tissues of the valve itself, either due to infection or failure of individual valve components.
Medgadget: How is the condition typically treated? What are the challenges inherent in treating it?
Mark Barrish: Surgery treats only a small portion (less than about 2%) of MR patients. For example, if a young and otherwise healthy patient with acute MR is identified early, they may undergo open-heart surgery or robotically assisted laparoscopic surgery. For these surgeries the heart is stopped, the chamber is accessed through the heart wall, and the patient is supported by a heart-lung machine. The surgeon can then adjust valve tissues, attach support structures, or affix a replacement valve to the surrounding tissues of the heart. Surgical outcomes are highly skill dependent, and many MR patients are simply too frail to withstand the trauma these procedures impose on the heart and surrounding tissues.
Over the last decade a much less invasive option has become available. Rather than perforating the heart wall, a Transcatheter Edge-to-Edge Repair (TEER) implant or "clip" at the end of a flexible catheter shaft can be advanced through the vascular system into the heart. Using a series of mechanical actuators while viewing ultrasound and fluoroscopy images, the interventional cardiologist manipulates the clip within the heart to grasp the leaflets of the mitral valve adjacent the leak, permanently clipping a portion of the valve closed to prevent the backward flow of blood. TEER therapy is challenging to learn and perform, but a well-known 2018 COAPT study and data from almost 15,000 patents have shown that TEER provides advantages in morbidity, mortality, and quality of life, particularly when performed by experienced specialists (those who have performed more than 200 procedures and who are working at a large-volume TEER "center of excellence").
In 2019, seven years after FDA approval, TEER therapy finally helped more MR patients than surgery. Unfortunately, most of those procedures were performed at small-volume centers by less experienced doctors. Because of the non-intuitive nature of the mechanical clip delivery system, the difficulty of interpreting the remote imaging, and the nuances of clipping differing valve anatomies, these small-center doctors simply do not achieve the same benefits for their patients as the centers of excellence.
Medgadget: Please give us an overview of the Moray Medical Robotic Catheter and associated technology, and how it can be used to treat mitral heart valve failure.
Mark Barrish: Moray Medical's products will digitize the interface between the interventional cardiologist and their therapeutic tools, making it as easy to manipulate a clip inside the beating heart as it is to move a cursor across a computer screen. The Moray Clipper TEER implant is supported by a single-use catheter and advanced to the heart using standard interventional techniques. Once the Clipper implant enters the chamber bordering the mitral valve, the cardiologist mounts the catheter handle to a re-usable Moray Coral fluidic driver that is about the size and shape of a brick. The operator will then use Moray's Submersion digital interactive environment—in which real-time off-the-shelf imaging is integrated into a 3D robotic workspace—to move the implant through the heart chamber to the valve leaflets. The user drives the implant by moving Moray's Trident input device with one hand relative to the tissues shown in the Submersion display.
In response, the Coral driver changes the position and orientation of the implant with corresponding movements, facilitating alignment of the implant with the displayed tissues. Throughout this process the real-time tissue images are augmented with easily understood virtual images of the Clipper system to provide clear 3D situational awareness. The combination makes implementing movements of the clip almost trivial, freeing the operator to concentrate on the nuances of the hemodynamics and tissues of their patient. Once the Clipper i mplant is aligned with the leaflets of the mitral valve, the catheter remains in a fixed position so that the operator can manually engage the implant against the valve tissues and deploy the clip using the same tactile feedback as is provided by existing TEER implants.
Medgadget: How does the system compare with conventional equipment for percutaneous interventions in terms of complexity and ease of use?
Mark Barrish: The complexity of percutaneous interventional tools varies widely. Many of the interventional tools in common use are for stenting. These tools need to navigate within the branching coronary vasculature to gain alignment with a diseased segment of a lumen, where the stent can be expanded radially to engage and hold open the luminal wall. Decades of evolution in these tools have produced specialized guidewires and catheters that are refined, simple, and low in cost, and a large population of interventional cardiologists have developed impressive skills allowing them to quickly and reliably advance the tool shafts axially, rotating pre-bent ends into target luminal branches from outside the patient under the guidance of fluoroscopic imaging.
Structural heart specialists operate within the same broad interventional cardiology space but treat the valves and other tissue structures using tools that are often much more complex. For example, existing TEER therapies take advantage of standard interventional tools to access the vasculature and advance to the heart. However, TEER clips and other structural heart tools need to be aligned—in both position and orientation—with specific tissues bordering the open heart chambers. This is often much more challenging, and the mechanical systems now used to deliver these therapies are often much more complex.
In fact, disposable drive assemblies used by prior mechanical TEER systems have included well over 1000 unique mechanical components—which are all discarded after a single use. Moray maintains the simple and efficient access to the heart derived from stent therapies, but the fluid-driven single-use Moray Clipper TEER catheter has only 15 mechanical steering components, and even Moray's re-usable Coral robotic fluid driver has less than 200 total components. The intuitive interaction provided by this robotic technology is also much easier to learn, more precise and repeatable, and will enable thousands of interventional cardiologists to treat the MR of millions of their patients.
Medgadget: Why are augmented reality and a 3D digital interface important in effectively using the catheter?
Mark Barrish: When the interventional cardiologist performs a robotic TEER therapy they cannot directly or optically see the valve tissues. Fluoroscopy provides a useful overall roadmap of the area, but the valve leaflets themselves are also not easily visible in those images. To grasp and clip these leaflet structures the operator needs to guide movement of the Clipper implant with reference to echocardiography (echo) images, typically bi-plane or 3D images from a Trans-Esophageal Echo (TEE) probe, a Trans-Thoracic Echo (TTE) probe, and/or an Intra-Coronary Echo (ICE) probe. Coordinating these different images from different sources at different orientations can be a challenge, particularly when trying to accurately position a clip in 3D despite differing views being shown in a side-by-side arrangement. The challe nge can be even greater for interventional cardiologists who may have less experience interpreting multi-plane echo displays. Moray's Submersion virtual reality environment helps overcome this challenge by aligning different real-time images in a coherent 3D robotic workspace that also contains a virtual model of the Moray Clipper robotic TEER system. Virtual images of the Clipper implant and its supporting catheter can be clearly and understandably projected onto the live image streams, helping the interventional cardiologist to kno w where the implant is relative to the defective valve tissue and how to move the implant efficiently and safely to exactly where he/she wants it.
Medgadget: How does the system affect procedure time and outcomes?
Mark Barrish: The precision, ease of use, and efficiency of Moray Medical's Clipper robotic TEER therapy system have real benefits for patients, health care providers, and the private and public entities which pay for these therapies. The overarching benefit to patients will be the expanded availability of TEER therapy to treat their MR. Moray also expects our pivotal study to establish significant benefits in patient safety and efficacy in the small-volume centers that already perform the bulk of TEER procedures. The reduced learning curve and ease of maintaining proficiency provided by Moray's robotic TEER therapy will benefit the clinical staff at regional hospitals and local cardiology groups, and will enable them to effectively treat their patients with MR, rather than having to refer them to distant (and often more expensive) centers of excellence. Patients, providers, and payors will all benefit from the significant reduction in average procedure times of robotic TEER. Perhaps even more important is the reduced variability in the time it takes to perform TEER therapies, which could allow each doctor to confidently schedule more procedures in a single day.
Atopic dermatitis (AD) and psoriasis, two common chronic inflammatory skin diseases that are associated with various comorbidities. Circular RNA (circRNA) constitute a major class of non‐coding RNAs that have been implicated in many human diseases, although their potential involvement in inflammatory skin diseases remains elusive. Here, we compare and contrast the circRNA expression landscapes in paired lesional and non‐lesional skin from psoriasis and AD patients relative to skin from unaffected individuals using high‐depth RNA‐seq data. CircRNAs and their cognate linear transcripts were quantified using the circRNA detection algorithm, CIRI2, and in situ hybridization and Sanger sequencing was used for validation purposes. We identified 39,286 circRNAs among all samples and found that psoriasis and AD lesional skin could be distinguished from non‐lesional and healthy skin based on circRNA expression landscapes. In general, circRNAs were less abundant in lesional relati ve to non‐lesional and healthy skin. Differential expression analyses revealed many significantly downregulated circRNAs, mainly in psoriasis lesional skin, and a strong correlation between psoriasis and AD‐related circRNA expression changes was observed. Two individual circRNAs, ciRS‐7 (also known as CDR1as) and circZRANB1, was specifically dysregulated in psoriasis and show promise as biomarkers for discriminating AD from psoriasis. In conclusion, the circRNA transcriptomes of psoriasis and AD share expression features, including a global downregulation relative to healthy skin, but this is most pronounced in psoriasis, and only psoriasis is characterized by several circRNAs being dysregulated independently of their cognate linear transcripts. Finally, specific circRNAs could potentially be used to distinguish AD from psoriasis.
Physician rating of cutaneous erythema is central to clinical dermatological assessment as well as quantification of outcome measures in clinical trials in a number of dermatologic conditions. However, issues with interrater reliability and variability in the setting of higher Fitzpatrick skin types makes visual erythema assessment unreliable.
Aim
To develop and validate a computer‐assisted image‐processing algorithm (EQscore) to reliably quantify erythema (across a range of skin types) in the dermatology clinical setting.
Methods
An image processing algorithm (EQscore) was developed to evaluate erythema based upon green‐light suppression differentials between affected and unaffected skin. A group of 4 dermatologists used a 4‐point Likert scale as a human evaluation of similar erythematous patch tests. Algorithm and dermatologist scores were compared across 164 positive patch test reactions. The intra‐class correlation coefficient of groups and the correlation coefficient between groups were calculated. The EQscore was validated on and independent image set of psoriasis, minimal erythema dose testing, and steroid‐induced blanching images.
Results
The reliability of the erythema quantification method produced an intra‐class correlation coefficient of 0.84 for the algorithm and 0.67 for dermatologists. The correlation coefficient between groups was 0.85. The EQscore was able to quantify erythema.
Conclusion
The EQscore demonstrated high agreement with clinical scoring and superior reliability compared with clinical scoring, avoiding the pitfalls of erythema underrating in the setting of pigmentation. The EQscore is easily accessible, user‐friendly, and may allow dermatologists to more readily and accurately rate the severity of dermatological conditions and the response to therapeutic treatments.
Cutaneous lichen planus (CLP) and psoriasis (PSO) are both common chronic inflammatory skin diseases for which development of new treatments requires the identification of key targets. While PSO is a typical Th17/IL‐17‐disorder, there is some evidence that Th1/IFN‐ɣ dominate the inflammatory process in CLP. Nonetheless, the immunopathogenesis of CLP is not fully explained and key immunological factors still have to be recognized. In this study, we compared the immune signature of CLP lesions with the well characterized inflammation present in PSO skin. First, we analyzed the histological and immunohistological characteristics of CLP and PSO. Second, we assessed the cytokine expression (IL1A, IL1B, IL4, IL6, IL8, IL10, IL17A, IL19, IL21, IL22, IL23A, IL13, IFNG, TNF, IL12A, IL12B, IL36G) of lesional skin of CLP with PSO by qPCR. Histology revealed a similar epidermal thickness in CLP and PSO. Immunohistochemically, both diseases presented with an inflammatory infiltra te mainly composed by CD3+CD4+ T cells rather than CD3+CD8+. Importantly, mRNA analysis showed a distinct cytokine signature: while levels of IL12B, IL1A, IL6 and IL23 were similar between the two groups, the characteristic PSO‐associated cytokines IL8, IL17A, IL22, IL19 and IL36G were expressed at very low levels in CLP. In contrast, CLP lesional skin was dominated by the expression of IFNG, IL21, IL4, IL12A, and TNF. Immunohistochemistry confirmed the dominance of IL‐21, IFN‐ɣ and also pSTAT1 in the dermal infiltrate of CLP, while IL‐17A was more present in PSO. Collectively, this study improves our understanding of the immunological factors dominating CLP. The dominating cytokines and signaling proteins identified suggest that future anti‐cytokine therapeutics like JAK inhibitors may be beneficial in CLP.
The past decade has seen the emergence of rehabilitation treatments using virtual reality. One of the advantages in using this technology is the potential to create positive motivation, by means of engaging en...
The use of Kigelia africana plant is beneficial in many medicinal applications. This study investigated the chemical compounds as well as antioxidant and antidiabetic activities of KA fruits in vitro and in vivo. Molecular docking study was used to predict the activities of these metabolites in relation to diabetes mellitus. From the result of GC-qTOF-MS, phenol-2,4-bis(1,1-dimethylethyl)-, benzene propanoic acid-3,5-bis(1,1-dimethylethyl)-4-hydroxymethylester, naphthalene-2-methyl-, and oxalic acid-4-chlorophenyl nonyl-ester were newly identified and revealed a strong binding affinity of − 6.1, − 6.3, − 6.8, and − 6.2 kcal/mol respectively. The hexane and ethyl acetate fractions had the highest antioxidant activities with 0.14 and 0.025 mg/mL for DPPH; 91.31 and 99.20 mg AAE/g for FRAP; and 80.61 and 98.88 mg AAE/g for TPC, respectively. Hexane fraction (HF) had the lowest IC50 value (1.97 mg/mL) against α-amylase. At low and middle doses, HF showed significant ameliorative activities by restoring islet cells, increasing the number of β cells, and reducing fasting blood glucose levels. Significant differences were observed in the activities of GGT and G-6-PDH. KA fruit exhibited high antidiabetic and antihyperglycemic activities in STZ-induced diabetic rats. According to molecular docking study, the use of the base structure of 2,4-ditert-butylphenol identified from K. africana fruit may serve as the novel approach to the treatment of diabetes mellitus.
Mitochondrial cardiomyopathy can be described as a condition characterized by abnormal heart-muscle structure and/or function, secondary to mutations in nuclear or mitochondrial DNA. Its severity can range from subclinical to critical conditions. We presented three cases of mitochondrial cardiomyopathy with m.3243A > G mutation and compared the clinical manifestations with the histological findings for each of these cases. All cases showed cardiac hypertrophy, juvenile-onset diabetes mellitus, and hearing loss. Case 1 (43-year-old male) showed less cardiac involvement and shorter duration of mitochondrial disease-related symptoms than case 2 (67-year-old female) and case 3 (51-year-old male), who showed the most advanced cardiac condition and longest duration from the manifestation of heart failure. The histological findings revealed that cardiomyocytes from case 1 showed no hypertrophy and mitochondrial degeneration in electron microscopy. Alternatively, cases 2 and 3 showed hypertrophy in their cardiomyocytes, and mitochondrial degeneration (e.g. onion-like lesions, swollen cristae, and lamellar bodies) was most apparent in case 3. These results suggested that mitochondrial degeneration, as evaluated by electron microscopy, might be correlated with impaired heart function in patients with mitochondrial cardiomyopathy.
Vemurafenib, ein BRAF‐Inhibitor, weist als häufige kutane Nebenwirkung eine erhöhte Photosensitivität auf, die sich klinisch im Auftreten eines sofortigen Hitzegefühls und eines ödematösen Erythems bei Sonnenexposition sowie einer Sonnenbrandreaktion im Sinne einer Spätreaktion äußert. Phototestungen konnten sowohl für die Sofortreaktion als auch für die Spätreaktion ein Aktionsspektrum im UVA‐Bereich (320 nm bis 400 nm) belegen. Pathogenetisch legten photochemische Untersuchungen nahe, dass UVA‐Bestrahlung von Vemurafenib unter bestimmten Bedingungen ein UVA‐absorbierendes Photoprodukt produziert. Auch in vitro konnte an verschiedenen Zellmodellen die phototoxische Wirkung von Vemurafenib ausschließlich im UVA‐Bereich nachgewiesen werden. Bei der klinisch zu beobachtenden Lichtempfindlichkeit dominiert wahrscheinlich dieser Mechanismus.
Andererseits kann Vemurafenib zusätzlich die Ferrochelatase inhibieren, was zu einem Anstieg von Protoporphyrin IX führt, der auch in einigen Untersuchungen beim Menschen unter Einnahme von Vemurafenib nachgewiesen wurde. Ob die Porphyrine tatsächlich insbesondere zur Symptomatik der Sofortreaktion beitragen, die klinisch der erythropoetischen Protoporphyrie (EPP) mit einem vergleichbaren Pathomechanismus ähnelt, ist noch nicht abschließend geklärt.
Andere BRAF‐Inhibitoren wie Dabrafenib und Encorafenib weisen eine deutliche geringere Photosensitivität auf. Patienten, die mit Vemurafenib therapiert werden, müssen auf die bereits durch geringe UVA‐Dosen auslösbaren Sofort‐ und Spätreaktionen hingewiesen werden und hinsichtlich photoprotektiver Maßnahmen beraten werden.
Die atopische Dermatitis ist eine der häufigsten chronisch entzündlichen Hauterkrankungen. Die Pathomechanismen der atopischen Dermatitis wurden in den letzten Jahren immer besser verstanden. Dies kann zukünftig dazu beitragen, verschiedene Endotypen zu identifizieren, die für bestimmte Therapien bevorzugt geeignet sind. Eine patientenadaptierte Therapie berücksichtigt neben dem phänotypischen Erscheinungsbild genetische und biologische Merkmale. Die aktuelle Entwicklung von Biologika und kleinmolekularen Medikamenten zur Behandlung der atopischen Dermatitis wird im vorliegenden Artikel vorgestellt. Diese Moleküle werden, wenn sie zugelassen werden, die Therapieperspektiven in der Zukunft verändern.
Dupilumab ist als erstes Biologikum bereits zur Behandlung der atopischen Dermatitis bei Jugendlichen und Erwachsenen zugelassen und hat die Behandlung von Patienten mit mittelschwerer und schwerer atopischer Dermatitis verbessert. In der vorliegenden Arbeit werden eigene Real‐Life‐Daten zur Wirksamkeit von Dupilumab bei der atopischen Dermatitis vorgestellt. Darüber hinaus werden weitere relevante Daten gezeigt, die in der praktischen Anwendung von Dupilumab eine Rolle spielen, und offene Fragen werden diskutiert.
Wöchentlich dreimalige Anwendung kalten atmosphärischen Plasmas (KAP) wurde bereits erfolgreich zur Wundbehandlung eingesetzt. Jetzt sollte untersucht werden, ob mit nur einmal wöchentlicher Behandlung vergleichbar gute Ergebnisse erzielt werden können.
Patienten und Methodik
In dieser randomisierten klinischen Pilotstudie (RCT) wurden Patienten mit therapierefraktären chronischen Wunden über maximal zwölf Wochen 1 x/Woche (Gruppe 1) oder 3 x/Woche (Gruppe 2) mit KAP behandelt. Patienten der Gruppe 3 erhielten 1 x/Woche eine Placebotherapie.
Ergebnisse
Die Wundfläche nahm in Gruppe 1 (n = 14) signifikant um 63,0 % (P = 0,005) und in Gruppe 2 (n = 13) um 46,8 % (P = 0,007) ab. In Gruppe 3 (n = 10) wurden die Wunden durchschnittlich 17,5 % größer. In den beiden mit KAP behandelten Gruppen konnte eine signifikante Schmerzreduktion (Gruppe 1: P = 0,042; Gruppe 2: P = 0,027) gemessen werden. Ausschließlich in der Gruppe 2 zeigte sich eine signifikante Verbesserung der wundspezifischen Lebensqualität (P = 0,005). Nach der zwölfwöchigen KAP‐Behandlung konnte eine Reduktion der Bakterienlast um durchschnittlich 50,4 % (Gruppe 1) beziehungsweise um 35,0 % (Gruppe 2) im Vergleich zum Tag des Studieneinschlusses nachgewiesen werden.
Schlussfolgerungen
Unserer RCT zeigt, dass durch die Behandlung mit KAP verschiedene Parameter der Wundheilung bei Patienten mit therapierefraktären, chronischen Wunden verbessert werden. Hierbei waren die Ergebnisse bei der Anwendung 1 x/Woche der Anwendung 3 x/Woche nicht unterlegen. Die Behandlung 1 x/Woche ist im klinischen Alltag leichter und wirtschaftlicher zu implementieren.
TEER implant is supported by a single-use catheter and advanced to the heart using standard interventional techniques. Once the Clipper
