Emerging Therapies of Traumatic Spinal Cord Injury

Research Article | DOI: https://doi.org/doi.org/10.31579/jsdr.2

Emerging Therapies of Traumatic Spinal Cord Injury

*Corresponding Author:

Citation:

Copyright: © Tengo Lika 2018 et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 30 November -0001 | Accepted: 02 May 2018 | Published: 09 May 2018

Keywords: Spinal cord injury; trauma; MRI; imaging; stem cell; neuroprotection; neuroregeneration

Abstract

Traumatic spinal cord injuries (SCIs) affect 1.3 million North Americans, producing devastating physical, social, and vocational impairment. Pathophysiologically, the initial mechanical trauma is followed by a significant secondary injury which includes local ischemia, pro-apoptotic signaling, release of cytotoxic factors, and inflammatory cell infiltration. Expedient delivery of medical and surgical care during this critical period can improve long-term functional outcomes, engendering the concept of “Time is Spine”. We emphasize the importance of expeditious care while outlining the initial clinical and radiographic assessment of patients. Key evidence-based early interventions (surgical decompression, blood pressure augmentation, and methylprednisolone) are also reviewed, including findings of the landmark Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). We then describe other neuroprotective approaches on the edge of translation such as the sodium-channel blocker riluzole, the anti-inflammatory minocycline, and therapeutic hypothermia. We also review promising neuroregenerative therapies that are likely to influence management practices over the next decade including chondroitinase, Rho-ROCK pathway inhibition, and bioengineered strategies. The importance of emerging neural stem cell therapies to remyelinate denuded axons and regenerate neural circuits is also discussed. Finally, we outline future directions for research and patient care.

Introduction

Traumatic spinal cord injuries (SCIs) have devastating consequences for patients and families. Direct lifetime costs can be as high as $1.1–$4.6 million per patient, with over 1.3 million patients affected in North America alone ¹^{, 2}. Expedient delivery of specialized medical and surgical care can improve long-term functional outcomes for patients ³^{, 4}. The rapidly evolving management of patients with SCI is summarized here with emphasis on evidence-based current practices and upcoming therapies in trial.

Pathophysiology

The initial primary trauma results in mechanical injury to cells, damages the sensitive microvasculature of the cord, and causes hemorrhage. Pro-apoptotic signaling is initiated and progressive edema contributes to ongoing ischemia ⁵^{, 6}. Furthermore, the blood-spinal cord barrier is disrupted, permitting an influx of vasoactive peptides, cytokines, and inflammatory cells ⁷^{, 8}. Over the ensuing hours to days, by-products of cellular necrosis are released (ATP, DNA, and K ⁺), creating a cytotoxic post-injury milieu and activating microglia to further recruit phagocytes. Macrophages and polymorphonuclear leukocytes infiltrate and generate oxygen free radicals and other cytotoxic by-products.

As the parenchymal volume is lost, cystic cavities coalesce, creating a physical barrier to cell migration ¹¹. Furthermore, the lack of structural framework impedes regenerative attempts. Over time, astrocytes proliferate and surround the perilesional zone, creating an irregular mesh-like barrier of interwoven cell processes ¹². This is accompanied by fibroblast deposition of chondroitin sulfate proteoglycans (CSPGs) including neural/glial antigen 2 (NG2) and tenascin ¹³^{– 16}. CSPGs and myelin glycoproteins act via the Rho-ROCK (rho-associated protein kinase) pathway to inhibit neurite outgrowth by signaling growth cone collapse through effector kinases ¹⁷. Together, these mechanisms severely restrict endogenous neural circuit regeneration and oligodendrocyte remyelination at a cellular level.

Systemically, cervical and thoracic cord injuries can interrupt the sympathetic output of the intermediolateral column, causing neurogenic shock with loss of peripheral vascular tone and bradycardia ¹⁸. The result can be profound hypotension, which further exacerbates cord ischemia ¹⁹. Paralysis of the intercostal and abdominal muscles restricts the inspiratory phase of ventilation, leading to hypercarbia and/or hypoxia. Furthermore, a weakened cough, poor mobilization, and secondary immunodeficiency (immune paralysis) after SCI make patients highly susceptible to life-threatening infections ²⁰^{, 21}.

Methods

Data sources

The NSCID began in 1973 and is believed to capture data from approximately 13% to 15% of new SCIs every year in the United States. Since its inception, 28 federally funded SCI Model System centers have contributed data to NSCID, including demographics, injury and medical characteristics, and functional independence during the initial hospitalization and at postinjury years 1 and 5 and every 5 years thereafter.²⁰ Psychosocial outcomes and assistive technology information have also been obtained at each follow-up. The NSCID defines SCI as the occurrence of an acute traumatic lesion of neural elements in the spinal canal, resulting in temporary or permanent sensory and/or motor deficit. The clinical definition of SCI excludes intervertebral disc disease, vertebral injuries in the absence of SCI, nerve root avulsions and injuries to nerve roots and peripheral nerves outside the spinal canal, cancer, spinal cord vascular disease, and other nontraumatic spinal cord diseases. Details about this database have been described elsewhere.²¹

Study participantsThe present analyses are limited to persons enrolled in the NSCID and NSSCID who sustained a traumatic SCI between 2005 and 2011 (N=7,882). After excluding those with unknown etiology of injury (n=48), a total of 7,429 persons from 19 SCI Model System Centers and 405 persons from the 3 Shriners SCI units were included in this study. The participating SCI Model System centers and corresponding sample size are as follows: Alabama (n=432), California (n=76, from 2 centers), Colorado (n=946), District of Columbia (n=197), Florida (n=41), Georgia (n=1,907), Illinois (n=350), Massachusetts (n=232), Michigan (n=243), Missouri (n=34), New York (n=286), New Jersey (n=485), Ohio (n=265), Pennsylvania (n=968, from 2 centers), Texas (n=482), Virginia (n=29), and Washington (n=456).

Demographic and injury profile of study participants (N=7 Age group, years
0-15 (21.5)
61 and above Sex
Male Race
White, Non-Hispanic (66.8)
Black, Non-Hispanic Level of injury
C1-C4 –
Completeness of injury (AIS)
A Day of injury
Monday (11.7)
Wednesday Month of injury
January (9.1)
September Table 1 shows the participants’ characteristics. Note: AIS = American Spinal Injury Association Impairment Scale. Discussion Demographic and injury profiles of the 7,834 persons with SCI enrolled in the NSCID and NSSCID in the past 7 years are generally consistent with previous findings from the population-based studies in the United States during the 1970s to 1990s that reported a higher SCI incidence in males, among those 16 to 30 years of age, among blacks (particularly violence-related SCIs), and during weekends and warmer months.⁶^{,7, 9, 10, 16, 25-27} The present study findings of substantial variations of specific etiologies of injury by age, sex, race/ethnicity, day, and month further highlight the need for prevention strategies to be tailored to the targeted population and major causes of SCI to increase their impact on reducing the incidence of SCI. The strongest efforts at preventing SCI should focus on young males and automobile crashes. Prevention targeting blacks must address violence issues. Prevention programs designed for adolescents and young adults should address risk-taking behaviors, whereas prevention programs for the elderly should be aimed at falls. The observation of a strong relationship between etiologies and level/completeness of injury also provides insight regarding the mechanisms of injury, which will aid in the design of equipment and other safety measures to reduce the incidence of SCI. In addition to personal characteristics and mechanical causes, there are behavioral and environmental factors that need to be considered in the development and coordination of prevention efforts, for instance, alcohol use, seatbelt use, distracted driving, road conditions, laws and law enforcement, which are beyond the scope of this study. Conclusion Prevention of SCI must be multifaceted and consider personal characteristics and mechanical causes as well as the social and political context of the injury. As prevention programs likely compete for recognition of benefits and costs against other regional and national agendas and resource priorities, strategies should be aimed at the targeted population and major causes to have the greatest impact on reducing the incidence of SCI. The present study sheds light on recent statistics of the etiology of SCIs in the United States with the hope of developing and implementing cost-effective prevention programs in the years to come. References Marino RJ, Ditunno JF, Jr, Donovan WH, Maynard F., Jr Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems. Arch Phys Med Rehabil. 1999;80:1391–1396 View at Publisher \| View at Google Scholar Fawcett JW, Curt A, Steeves JD, et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord. 2007;45:190–205 View at Publisher \| View at Google Scholar DeVivo MJ, Chen Y, Mennemeyer ST, Deutsch A. Costs of care following spinal cord injury. Top Spinal Cord Inj Rehabil. 2011;16:1–9 View at Publisher \| View at Google Scholar Cao Y, Chen Y, DeVivo MJ. Lifetime direct cost after spinal cord injury. Top Spinal Cord Inj Rehabil. 2011;16:10–16 View at Publisher \| View at Google Scholar Cripps RA, Lee BB, Wing P, Weerts E, Mackay J, Brown D. A global map for traumatic spinal cord injury epidemiology: towards a living data repository for injury prevention. Spinal Cord. 2011;49:493–501 View at Publisher \| View at Google Scholar Woodruff BA, Baron RC. A description of nonfatal spinal cord injury using a hospital-based registry. Am J Prev Med. 1994;10:10–14 View at Publisher \| View at Google Scholar Acton PA, Farley T, Freni LW, Ilegbodu VA, Sniezek JE, Wohlleb JC. Traumatic spinal cord injury in Arkansas, 1980 to 1989. Arch Phys Med Rehabil. 1993;74:1035–1040 View at Publisher \| View at Google Scholar Virginia Department of Rehabilitation Services Spinal Cord Injury in Virginia: A Statistical Fact Sheet. Fishersville, VA: Virginia Spinal Cord Injury System; 1993 View at Publisher \| View at Google Scholar Thurman DJ, Burnett CL, Jeppson L, Beaudoin DE, Sniezek JE. Surveillance of spinal cord injuries in Utah, USA. Paraplegia. 1994;32:665–669 View at Publisher \| View at Google Scholar Price C, Makintubee S, Herndon W, Istre GR. Epidemiology of traumatic spinal cord injury and acute hospitalization and rehabilitation charges for spinal cord injuries in Oklahoma, 1988-1990. Am J Epidemiol. 1994;139:37–47 View at Publisher \| View at Google Scholar Relethford JH, Standfast SJ, Morse DL. Trends in traumatic spinal cord injury - New York, 1982-1988. MMWR Morb Mortal Wkly Rep. 1991;40:535-537,543. View at Publisher \| View at Google Scholar Colorado Department of Public Health and Environment 1996 Annual Report of the Traumatic Spinal Cord Injury Early Notification System. Denver, CO: Colorado Department of Transportation Printing Office; 1997 View at Publisher \| View at Google Scholar Johnson AR, Lawrence DW. Spinal Cord Injury in Louisiana 1991 Annual Report. New Orleans, LA: Louisiana Office of Public Health; 1992 View at Publisher \| View at Google Scholar Johnson SC. Georgia Central Registry: Spinal Cord Disabilities and Traumatic Brain Injury. Warm Springs, GA: Roosevelt Warm Springs Institute for Rehabilitation; 1992 View at Publisher \| View at Google Scholar Buechner JS, Speare MC, Fontes J. Hospitalizations for spinal cord injuries, 1994-1998. Med Health R I. 2000;83:92–93 View at Publisher \| View at Google Scholar Surkin J, Gilbert BJ, Harkey HL, III, Sniezek J, Currier M. Spinal cord injury in Mississippi. Findings and evaluation, 1992-1994. Spine. 2000;25:716–721 View at Publisher \| View at Google Scholar Warren S, Moore M, Johnson MS. Traumatic head and spinal cord injuries in Alaska (1991-1993). Alaska Med. 1995;37:11–19 View at Publisher \| View at Google Scholar DeVivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord. 2012;50:365–372 View at Publisher \| View at Google Scholar National Spinal Cord Injury Statistical Center 2011 Annual Statistical Report for the Spinal Cord Injury Model Systems. Birmingham, AL: University of Alabama at Birmingham, National Spinal Cord Injury Statistical Center; 2011. View at Publisher \| View at Google Scholar Chen Y, Deutsch A, DeVivo MJ, et al. Current research outcomes from the spinal cord injury model systems. Arch Phys Med Rehabil. 2011;92:329–331 View at Publisher \| View at Google Scholar Stover SL, DeVivo MJ, Go BK. History, implementation, and current status of the National Spinal Cord Injury Database. Arch Phys Med Rehabil. 1999;80:1365–1371. View at Publisher \| View at Google Scholar Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain. Dr Aline Tollet Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources. Virginia E. Koenig Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all. Delcio G Silva Junior Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal. Ziemlé Clément Méda Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration. Mina Sherif Soliman Georgy We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal. Layla Shojaie The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent. Sing-yung Wu Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal. Orlando Villarreal Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field. Katarzyna Byczkowska Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive. Anthony Kodzo-Grey Venyo Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal. Pedro Marques Gomes Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI. Bernard Terkimbi Utoo This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal. Prof Sherif W Mansour Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers. Hao Jiang As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders. Dr Shiming Tang Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal. Raed Mualem International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous. Andreas Filippaios Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article. Dr Suramya Dhamija Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site. Bruno Chauffert I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day! Baheci Selen "We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay". Jesus Simal-Gandara I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work. Douglas Miyazaki We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future. Dr Griffith I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells. Dr Tong Ming Liu I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office. Husain Taha Radhi I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues. S Munshi Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments. Tania Munoz “The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”. George Varvatsoulias Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao. Rui Tao Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal. Khurram Arshad Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you. Gomez Barriga Maria Dolores The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time. Lin Shaw Chin Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort. Maria Dolores Gomez Barriga Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term. Dr Maria Dolores Gomez Barriga Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨. Dr Maria Regina Penchyna Nieto Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies. Dr Marcelo Flavio Gomes Jardim Filho Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!” Zsuzsanna Bene Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner Dr Susan Weiner My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews. Lin-Show Chin My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal. Sonila Qirko My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript. Luiz Sellmann I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office. Zhao Jia Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good." Thomas Urban I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews. Cristina Berriozabal To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field. Dr Tewodros Kassahun Tarekegn "I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work". Dr Shweta Tiwari I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications. Dr Farooq Wandroo Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article. Dr Anyuta Ivanova We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections. Dr David Vinyes My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts. Gertraud Teuchert-Noodt To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina Dr Elvira Farina Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy. Dr Oleg Golyanovski Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association. Dr Susan Anne Smith Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian. Dr Farahnaz Fallahian Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye. Dr Victor Olagundoye Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association. Dr Susan Anne Smith Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD Dr Eric S Nussbaum Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication. Hala Al Shaikh Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra. Dr Rakhi Mishra Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen. Dr Walter F Riesen Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga. Dr Jelle Lettinga Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora Dariusz Ziora Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava. Dr Ravi Shrivastava Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain. Dr Aline Tollet Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources. Virginia E. Koenig Quick Links Home Explore Journals Open Access Authors Editors About Us Submit Manuscript Explore Journals Article Processing Charges Peer Review at Auctores Submission Guidelines News letter Get latest update, news & journal offers Subscribe! Contact AUCTORES PUBLISHING LLC, 16192 Coastal Highway, Lewes , DE 19958, USA Phone: +1-(302)-520-2644 Email: info@auctorespublishing.com Contact Us (We contact you) © 2017-2025 Auctores Online, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use. Creative Commons License Open Access by Auctores Online is licensed under a Creative Commons Attribution 4.0 International License.