News Article | May 9, 2017
Two Studies Presented at DDW 2017 Showed Clinically Meaningful Reduction in Symptoms and Withdrawal or Reduction in Proton Pump Inhibitor Use by Two-Thirds of Patients Following Treatment with MUSE™ System Separate Presentation Supports HOF Criteria as a Potential Endoscopic Selection Criteria to Predict Amount of Reflux and Improve Treatment Outcomes OMER, ISRAEL--(Marketwired - May 9, 2017) - Medigus Ltd. ( : MDGS) ( : MDGS), a medical device company developing minimally invasive endosurgical tools and a leader in direct visualization technology, today announced results from three clinical studies involving the company's MUSE™ System, a minimally invasive solution for gastroesophageal reflux disease (GERD). The data were presented in three posters at Digestive Disease Week® (DDW), taking place in Chicago from May 6-9, 2017. The MUSE system is a single-use flexible transoral stapler that merges the latest advancements in microvisual, ultrasonic and surgical stapling. The device comes equipped with an ultrasonic sight and range finder and a micro ScoutCam™ CMOS camera, which enables a single physician to perform an incisionless transoral fundoplication -- the procedure is intended to treat the anatomical cause of gastroesophageal reflux disease (GERD), commonly known as acid reflux. Giorgia Mazzoleni, fellow at the San Raffaele Scientific Institute at the San Raffaele Hospital in Milan, Italy, presented a poster entitled, "Transoral Anterior Fundoplication (TAF) with Medigus Ultrasound Surgical Endostapler (MUSE™) for the Treatment of Gastroesophageal Reflux Disease (GERD); 6-Month Results from a Single-Center Prospective Study," which enrolled 24 GERD patients to assess the six-month safety and efficacy of TAF with MUSE. GERD quality of life questionnaires (HRQL) improved from a baseline of 43 to 18 six months after TAF with MUSE (p < 0.003). The study also highlighted an improvement in Reflux Symptom Index (RSI), from 21 to 10 (p < 0.009). A 79% reduction or withdrawal in PPI therapy was observed six-months after treatment, with 50% of patients stopping PPI use, 28.6% of patients halving PPI use, and 21.4% remaining on the same dose prior to treatment with TAF with MUSE. Dr. Ali Lankarani, board member of the Advanced Therapeutic Endoscopy Center (ATEC) at the Broland-Groover Clinic in Jacksonville, FL, presented a poster titled, "Interim Results From A Multi-Center Post-Marketing Surveillance Registry Study for Endoscopic Anterior Fundoplication," reported data from an ongoing post-market registry study of 68 GERD patients who underwent Endoscopic Anterior Fundoplication (EAF) in 13 international centers. GERD-HRQL improved from 24.0 to 6.0 following treatment with MUSE (CI, 13.4 - 20.8, p < 0.00001), demonstrating patients experienced a clinically meaningful reduction in GERD-related symptoms. In addition, baseline patient satisfaction was reported at 0%, but improved to 70% (26/37) at 6 months and 90% (9/10) at 1 year. Of note, 76% (28/37; p < 0.00001) of patients have eliminated or reduced their use of proton pump inhibitors (PPI), with 96% of patients that responded favorably to treatment with the MUSE System stopping daily PPI therapy. Dr. Lankarani remarked, "These interim results, in conjunction with the data from the single-center study presented by Mazzoleni, highlight how the MUSE System can be a revolutionary, minimally-invasive treatment option for patients with GERD who are unsatisfied with PPI therapeutics and hesitant to pursue surgical intervention. In addition to the impressive findings, in another study we were able to access the value of the HOF criteria over the Hill classification, which we believe will play a pivotal role alongside the MUSE System in improving overall treatment outcomes in GERD." In addition, Dr. Lankarani presented a second poster, entitled, "Endoscopic Predictors of Decreased Reflux After Endoscopic Anterior Fundoplasty," which evaluated the HOF criteria as an endoscopic grading system of gastroesophageal junction (GEJ) geometry, as well as selection criteria to guide treatment decisions and predict treatment outcomes. Currently, Hill classification is the most commonly used criteria for antireflux procedures, however it has limited utility and still results in one-third of EAF-treated patients to continue experiencing reflux. HOF criteria categorizes GEJ geometry based on measurement of axial length of hiatal hernia (H), hiatus opening dimension (O) and flap valve size (F), with H and O openings less than 1cm considered normal (N) and 1cm or larger categorized as abnormal (A). GEJ is categorized as AAA if all three HOF landmarks are abnormal, NAA if one HOF landmark is normal and two are abnormal, and NNN if all three HOF landmarks are normal. Using the HOF criteria, the researchers identified and successfully treated 18 GERD patients, with Total Present of Time spent in Reflux (TPTR) showing a reduction in all patients with NAA configuration, and 75% and 71% TPTR reduction in individuals that had a 1 and 2 cm hiatal hernia, respectively. Average TPTR improvement was 53% for the NAA configuration patients, while average TPTR improvement in patients with 1 and 2 cm hiatal hernia was 56% and 46%, respectively. Chris Rowland, Chief Executive Officer of Medigus, commented, "As the developers of a completely new, minimally invasive solution for the treatment of GERD, we are extremely motivated by data presented this year at DDW. We are pleased with the results reported from the single center study, and look forward to continuing the ongoing post-market multi-center study, which have shown promising reductions in PPI reliance, as well as increases in patient quality of life and satisfaction. These studies continue to support the use of our MUSE System, which can reduce the need for pharmaceuticals and invasive surgical procedures." To learn more about MUSE, visit: www.medigus.com Medigus is a medical device company specializing in developing minimally invasive endosurgical tools and highly innovative imaging solutions. They are the pioneer developer of the MUSE™ system, an FDA cleared and CE marked endoscopic device to perform Transoral Fundoplication (TF) for the treatment of GERD (gastroesophageal reflux disease), one of the most common chronic conditions in the world. In 2016, the CMS established the Category I CPT® Code of 43210 for TF procedures, such as the ones performed with MUSE, which establishes reimbursement values for physicians and hospitals. MUSE is gaining adoption in key markets around the world -- it is available in world-leading healthcare institutions in the U.S., Europe and Israel. Medigus is also in the process of obtaining regulatory clearance in China. Medigus is traded on the Nasdaq Capital Market and the TASE (Tel-Aviv Stock Exchange). To learn more about the company's advanced technology, please visit www.medigus.com or www.RefluxHelp.com. This press release may contain statements that are "Forward-Looking Statements," which are based upon the current estimates, assumptions and expectations of the company's management and its knowledge of the relevant market. The company has tried, where possible, to identify such information and statements by using words such as "anticipate," "believe," "envision," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," "contemplate" and other similar expressions and derivations thereof in connection with any discussion of future events, trends or prospects or future operating or financial performance, although not all forward-looking statements contain these identifying words. These forward-looking statements represent Medigus' expectations or beliefs concerning future events, and it is possible that the results described in this news release will not be achieved. By their nature, Forward-Looking Statements involve known and unknown risks, uncertainties and other factors which may cause future results of the company's activity to differ significantly from the content and implications of such statements. Other risk factors affecting the company are discussed in detail in the Company's filings with the Securities and Exchange Commission. Forward-Looking Statements are pertinent only as of the date on which they are made, and the company undertakes no obligation to update or revise any Forward-Looking Statements, whether as a result of new information, future developments or otherwise. Neither the company nor its shareholders, officers and employees, shall be liable for any action and the results of any action taken by any person based on the information contained herein, including without limitation the purchase or sale of company securities. Nothing in this press release should be deemed to be medical or other advice of any kind.
News Article | May 22, 2017
Paris, France: Promising results were reported in late-breaking trials with novel bioresorbable stent technologies at EuroPCR 2017, paving the way for ongoing developments in stents that are dissolved or reabsorbed after achieving vessel expansion in percutaneous coronary intervention procedures. Results from the prospective multicentre RENASCENT II study of the Amaranth Medical APTITUDE BRS stent, a novel ultra-high molecular weight poly-L-lactide BRS with a new, thinner strut (120 μm), reported no events at one year in 60 patients treated for single lesion coronary artery stenosis. Coronary artery imaging with optical coherence tomography (OCT) demonstrated excellent wall apposition and full, homogenous endothelial wall coverage, with no valleys and peaks between regions with struts and those without struts. "The results are very positive. The scaffold delivers a very low medium-term event rate and the stent favours good laminar flow in blood vessels," said lead author Antonio Colombo, from San Raffaele Scientific Institute, Milan, Italy, although he cautioned that the study was small. The key imaging results from the DESolve Nx Study, a prospective registry including 126 patients, showed a mean lumen gain of 9% at six months, as measured by intravascular ultrasound (IVUS), and an angiographic late luminal loss (LLL) of 0.2mm. "This is a clinical breakthrough as no other BRS technology has been successful in achieving such impressive results and, at the same time, degrading in six months with near complete resorption (mass loss) in one year," said lead author Stefan Verheye, from ZNA Middelheim, Antwerpen, Belgium. He added that the 18-month and 36-month imaging data showed sustained efficacy and confirmed the degradation and complete resorption (mass loss) in one year. There were no late or very late definite or probable scaffold thromboses and no target lesion revascularisations from years two to four. Verheye concluded, "Early degradation and early resorption is not only an intuitive wish, it is a must for a BRS technology in order to succeed. Companies attempted but failed to achieve clinical effectiveness, primarily due to chronic recoil of their scaffolds. In an effort to resolve this issue, companies had to revert to much longer degradation and resorption profiles. The Elixir DESolve scaffold is the only technology to date to resolve the chronic recoil issue, as evidenced by the Nx trial data." One-year results from the first-in-man MeRes-1 study of the safety and efficacy of the novel MeRes 100 scaffold in 108 patients with 116 de novo coronary artery lesions showed that the composite endpoint of cardiac death, myocardial infarction (MI) and ischaemia-driven target lesion revascularisation (ID-TLR) occurred in one patient (0.93%). There was no scaffold thrombosis. One-year computed tomography (CT) angiography demonstrated that all scaffolds were patent. Six-month quantitative coronary angiography showed a low rate of late lumen loss and no restenosis. Intravascular ultrasound and OCT analyses also gave favourable results, reported Ashok Seth, from Fortis Escort Heart Institute, New Delhi, India. He said, "The positive results of this study provide the basis for a larger, randomised trial against a second-generation metallic drug-eluting stent." Data were also reported for the following studies, but results were not available to include in the press release: Help for journalists to cover EuroPCR 2017 For any press-related inquiries, please contact: Register and attend EuroPCR 2017 as a journalist Press registration for EuroPCR is open to accredited journalists, free of charge. Journalists must hold a valid press card and/or provide a letter of assignment from a recognised publication. To register as press go to https:/ EuroPCR press releases EuroPCR press releases can be found at https:/ EuroPCR abstracts Abstracts are available online at https:/ Notes to Editors What is EuroPCR? EuroPCR, the official annual meeting of the European Association for Percutaneous Cardiovascular Interventions (EAPCI), a registered branch of the European Society of Cardiology, is the world-leading course in interventional cardiovascular medicine. PCR has established a distinctive format for educational activities in the field of cardiovascular interventions. Beyond its flagship course in Paris that gathers more than 11,500 participants every year, PCR organises annual courses in Singapore, London UK, Dubai EAU, Johannesburg RSA, Milan Italy, Chengdu China and Tokyo Japan. For further information on EuroPCR, PCR London Valves, PCR Peripheral, PCR-CIT China Chengdu Valves, GulfPCR-GIM, AsiaPCR, AfricaPCR, PCR Tokyo Valves, and all PCR activities, please contact: Célia Vilà: email@example.com. For more information, please visit: https:/ and follow us on Twitter https:/ using the hashtag #EuroPCR
Ferreri A.J.M.,San Raffaele Scientific Institute
The Lancet Oncology | Year: 2014
Extranodal lymphomas constitute a heterogeneous group of malignancies, accounting for roughly 60% of all non-Hodgkin lymphomas. The extranodal organ where lymphomas arise is an important determining factor of biological, molecular, and aetio-pathogenic features, and of presentation, dissemination pattern, and outcome. An increased risk of CNS involvement, an uncommon but lethal event, has been suggested in some extranodal lymphomas, but the absolute risk is still debatable for most of these malignancies. This debate is because of the presence of selection biases and other confounding factors in related literature, which inevitably has led to conflicting recommendations. The identification of extranodal lymphomas at increased risk of CNS dissemination is an important unmet clinical need; affected patients could benefit from early CNS assessment by neuroimaging and cerebrospinal fluid analysis and adequate CNS prophylaxis, avoiding unnecessary prophylaxis and related toxicity in low-risk patients. This Review discusses relevant confounding factors and identifies high-risk extranodal lymphomas analysing histopathological category, involved organ, and other specific risk factors, which could be helpful for result interpretation and patient stratification in future clinical trials. Finally, a recommendation is provided for CNS-directed management of high-risk extranodal lymphoma patients in daily practice. © 2014 Elsevier Ltd.
Ferreri A.J.M.,San Raffaele Scientific Institute
Blood | Year: 2011
Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials. Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials. © 2011 by The American Society of Hematology.
Hedlund P.,San Raffaele Scientific Institute
Neurourology and Urodynamics | Year: 2014
Aims: To review knowledge on cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. Methods: Review of MEDLINE using defined search terms, and manual analysis. Articles published in English were included. Results: and Discussion Components of the endocannabinoid system - cannabinoid (CB) receptor types 1 and 2, anandamide, and fatty acid amide hydrolase (FAAH), which degrades anandamide and related fatty-acid amides - have been located to lower urinary tract tissues of mice, rats, monkeys, and humans. Studies have located CB receptors in urothelium and sensory nerves and FAAH in the urothelium. CB receptor- and FAAH-related activities have also been reported in the lumbosacral spinal cord. Data on supraspinal CB functions in relation to micturition are lacking. Cannabinoids are reported to reduce sensory activity of isolated tissues, cause antihyperalgesia in animal studies of bladder inflammation, affect urodynamics parameters reflecting sensory functions in animals models, and appear to have effects on storage symptoms in humans. FAAH inhibitors have affected sensory bladder functions and reduced bladder overactivity in rat models. Cannabinoids may modify nerve-mediated functions of isolated lower urinary tract tissues. Conclusions: Evidence suggests components of the endocannabinoid system are involved in regulation of bladder function, possibly at several levels of the micturition pathway. It is unclear if either CB receptor has a dominant role in modification of sensory signals or if differences exist at peripheral and central nervous sites. Amplification of endocannabinoid activity by FAAH inhibitors may be an attractive drug target in specific pathways involved in LUTS. © 2013 Wiley Periodicals, Inc.
Tortoli E.,San Raffaele Scientific Institute
Clinical Microbiology Reviews | Year: 2014
Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the fact thatNTMare characterized by a moderate pathogenicity, the diseases caused by NTM at various body sites are increasing on a worldwide level. Among over 150 officially recognized NTM species, only two or three dozen are familiar to clinicians, and even to most microbiologists. In this paper, approximately 50 new species described in the last 8 years are reviewed, and their role in human infections is assessed on the basis of reported clinical cases. The small number of reports concerning most of the “new” mycobacterial species is responsible for the widespread conviction that they are very rare. Their role is actually largely underestimated, mainly because they often remain unrecognized and misidentified. Aiming to minimize such bias, emphasis has been placed on more common identification pitfalls. Together with new NTM, new members of the Mycobacterium tuberculosis complex described in the last few years are also an object of the present review. © 2014, American Society for Microbiology. All Rights Reserved.
Casucci M.,San Raffaele Scientific Institute
Blood | Year: 2013
Genetically targeted T cells promise to solve the feasibility and efficacy hurdles of adoptive T-cell therapy for cancer. Selecting a target expressed in multiple-tumor types and that is required for tumor growth would widen disease indications and prevent immune escape caused by the emergence of antigen-loss variants. The adhesive receptor CD44 is broadly expressed in hematologic and epithelial tumors, where it contributes to the cancer stem/initiating phenotype. In this study, silencing of its isoform variant 6 (CD44v6) prevented engraftment of human acute myeloid leukemia (AML) and multiple myeloma (MM) cells in immunocompromised mice. Accordingly, T cells targeted to CD44v6 by means of a chimeric antigen receptor containing a CD28 signaling domain mediated potent antitumor effects against primary AML and MM while sparing normal hematopoietic stem cells and CD44v6-expressing keratinocytes. Importantly, in vitro activation with CD3/CD28 beads and interleukin (IL)-7/IL-15 was required for antitumor efficacy in vivo. Finally, coexpressing a suicide gene enabled fast and efficient pharmacologic ablation of CD44v6-targeted T cells and complete rescue from hyperacute xenogeneic graft-versus-host disease modeling early and generalized toxicity. These results warrant the clinical investigation of suicidal CD44v6-targeted T cells in AML and MM.
ten Hacken E.,San Raffaele Scientific Institute
Blood | Year: 2013
HS1 (hematopoietic cell-specific Lyn substrate-1) is a cytoskeletal interactor in the B-cell receptor (BCR) signaling pathway whose phosphorylation correlates with prognosis in Chronic Lymphocytic Leukemia (CLL). The differentially phosphorylated sites and the kinases that regulate HS1 activity in CLL remain poorly understood. We demonstrate that HS1 activity is differentially regulated by LYN kinase that, in a subset of patients, phosphorylates HS1 on Tyrosine (Y)397, resulting in its activation. This correlates with increased cytoskeletal functionality in terms of migration, adhesion and F-actin polymerization. In these patients, LYN is also activated on Y396 residue and its inhibition with the tyrosine kinase inhibitor Dasatinib abrogates HS1-Y397 phosphorylation. This results in the reduction of HS1 activation along with that of cytoskeletal effector VAV1 and the downstream kinase ERK also in the presence of BCR and CXC chemokine receptor CXCR4 stimulation. Interestingly, targeting the LYN/HS1 axis in vitro leads to the concomitant reduction of cytoskeletal activity, BCR signaling and cell survival in the subset of patients with activated LYN/HS1. In a transplantable mouse model based on the EμTCL1 transgenic mouse, LYN/HS1 signaling inhibition interferes with CLL progression and lymphoid organ infiltration. Thus LYN/HS1 axis marks distinct signaling profiles and cytoskeletal-related features that may represent valuable targets for cytoskeleton-targeted therapeutic intervention in CLL.
Apollonio B.,San Raffaele Scientific Institute
Blood | Year: 2013
B-cell receptor (BCR) triggering and responsiveness have a crucial role in the survival and expansion of chronic lymphocytic leukemia (CLL) clones. Analysis of in vitro response of CLL cells to BCR triggering allowed the definition of 2 main subsets of patients and lack of signaling capacity was associated with constitutive activation of extracellular-regulated kinases 1/2 (ERK1/2) and nuclear factor of activated T cells c1 (NF-ATc1), consistent with the idea that at least one group of CLL patients derives from the abnormal expansion of anergic B cells. In the present work, we further investigated the anergic subset of CLL (defined as the one with constitutive ERK1/2 phosphorylation) and found that it is characterized by low levels of surface immunoglobulin M and impairment of calcium mobilization after BCR engagement in vitro. Chronic BCR triggering promoted CLL cell survival selectively in phosphorylated ERK1/2 samples and the use of mitogen-activated protein kinase and NF-AT signaling inhibitors specifically induced apoptosis in this group of patients. Apoptosis induction was preceded by an initial phase of anergy reversal consisting in the loss of ERK phosphorylation and NF-AT nuclear translocation and by the restoration of BCR responsiveness, reinforcing the idea that the anergic program favors the survival of leukemic lymphocytes.
Camaschella C.,San Raffaele Scientific Institute
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013
To avoid iron deficiency and overload, iron availability is tightly regulated at both the cellular and systemic levels. The liver peptide hepcidin controls iron flux to plasma from enterocytes and macrophages through degradation of the cellular iron exporter ferroportin. The hepcidin-ferroportin axis is essential to maintaining iron homeostasis. Genetic inactivation of proteins of the hepcidin-activating pathway causes iron overload of varying severity in human and mice. Hepcidin insufficiency and increased iron absorption are also characteristic of anemia due to ineffective erythropoiesis in which, despite high total body iron, hepcidin is suppressed by the high erythropoietic activity, worsening both iron overload and anemia in a vicious cycle. Hepcidin excess resulting from genetic inactivation of a hepcidin inhibitor, the transmembrane protease serine 6 (TMPRSS6) leads to a form of iron deficiency refractory to oral iron. Increased hepcidin explains the iron sequestration and iron-restricted erythropoiesis of anemia associated with chronic inflammatory diseases. In mice, deletion of TMPRSS6 in vivo has profound effects on the iron phenotype of hemochromatosis and beta-thalassemia. Hepcidin manipulation to restrict iron is a successful strategy to improve erythropoiesis in thalassemia, as shown clearly in preclinical studies targeting TMPRSS6; attempts to control anemia of chronic diseases by antagonizing the hepcidin effect are ongoing. Finally, the metabolic pathways identified from iron disorders are now being explored in other human pathologic conditions, including cancer.