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Stem cell transplantation for treatment of severe autoimmune diseases: current status and future perspectives.

Autoimmune diseases include a heterogeneous group of disorders with variable presentation and severity. Immunosuppressive and immunomodulatory therapies are often used for treatment with considerable success in some cases. These diseases may also be severe and refractory to conventional treatment. Thus more aggressive intervention might be indicated in a subset of patients. Animal studies suggest that high-dose therapy supported by stem cell transplantation may lead to remissions in experimental autoimmune disease models. Anecdotal case reports suggest that the same may be the case in some human autoimmune diseases as well. This review attempts to summarise some current concepts and future perspectives on stem cell transplantation in the treatment of severe autoimmune diseases.

Acute Disease↗

Robotics in laparoscopic surgery: current status and future perspectives.

BACKGROUND: Laparoscopic surgery has been introduced to limit the burden of surgical damage to the abdominal wall and peritoneum. METHODS: Description of procedure and results of robotic laparoscopic surgery. RESULTS: Laparoscopic surgery has resulted in reduction of postoperative pain, surgery-related complications and scarring. Laparoscopic techniques, however, are challenging for the surgeon owing to the disadvantages of inverted and restricted manipulation and the indirect two-dimensional view. In order to solve these problems, robotic telemanipulation systems were developed and introduced to the market at the end of the past decade. This article describes and discusses the current status and future perspectives of robotic systems in endoscopic surgery. CONCLUSION: Robotic laparoscopic surgery overcomes some of the disadvantages of conventional laparoscopic surgery.

Humans↗

Computer assisted orthopaedic and trauma surgery. State of the art and future perspectives.

In recent years computer technologies have become more and more integrated in surgical procedures. The potential advantages of computer assisted surgery (CAS) are: increase of accuracy of surgical interventions, less invasive operations, better planning and simulation and reduction of radiation exposure for both patient and surgeon. After introduction of CAS in neurosurgery, the clinical applications of this technique expanded also into trauma and orthopaedic surgery. The first application of this new technique in orthopaedic and trauma surgery was for placement of lumbar pedicle screws. After its introduction into spine surgery, CAS was applied in other fields of orthopaedic surgery like hip, knee and skeletal trauma surgery. In this article the technical background and the various clinical applications and future perspectives of computer assisted orthopaedic and trauma surgery are outlined.

Forecasting↗

Current status of left ventricular assist devices: the role in bridge to heart transplantation and future perspectives.

Increasing numbers of patients with end-stage heart failure are awaiting heart transplantation worldwide. Left ventricular assist systems have been applied to these patients with increasing frequency and support duration. This situation calls for more reliably applied long-term support devices and is also stimulating the investigation of destination therapy or bridge to recovery use of the device. This is particularly relevant in countries where organ shortages are crucial. However, reports in this area are still limited, and there exist several problems to be solved before wider application of these strategies is possible in clinical practice. We review currently available devices with special reference to their respective roles and limitations quoting our own experiences over the past several years, and discuss future perspectives of ventricular assist devices.

Adolescent↗

Minimally invasive surgery in prostate cancer: current and future perspectives.

Prostate cancer is a leading cause of death for men. Its prevalence increases substantially with advancing age, which coincides with increased incidence of comorbidities. The mainstay therapy for early prostate cancer remains radical surgery and radiotherapy. In the era of prostate-specific antigen and the newly emerging highly specific screening tests, more men are diagnosed earlier in their life and with confined disease. The application of minimally invasive approaches, such as the laparoscopic/telerobotic approach and focal treatments, is becoming more popular, yielding shorter hospital stays and faster recovery, with minimal complications. In part, this is possible due to groundbreaking advances in laparoscopic equipment, prostate imaging modalities, and gained urologic expertise in minimally invasive treatment. In this review we critically discuss the current knowledge and future perspectives of minimally invasive treatment in prostate cancer.

Cryotherapy↗

Present and future perspectives on children with type 1 diabetes.

This review presents current achievements in paediatric diabetology and discusses potential new approaches. Recent multinational investigations have demonstrated that in spite of multidisciplinary diabetes care only one-third of young patients with diabetes have an HbA1c below 8%, which is associated with a lower risk for development of secondary complications. Since there is no standard protocol for the optimal treatment of diabetes in children and adolescents, the therapy has to be tailored to the individual child's needs, involving not only paediatricians, but also dieticians, diabetes educators, psychologists and social workers. To improve the current situation a major goal for the next few years appears to be the establishment of standards for structure, process and outcome quality in paediatric diabetology. Future perspectives include possibilities for a cure via islet- or pancreas transplantation or improved pharmacological therapy following the introduction of new types of insulin or other beta cell-related peptides as adjunctive therapy not currently used.

Adolescent↗

Matrix metalloproteinase inhibitors: current developments and future perspectives.

Malignant tumors are characterized by invasive growth and metastasis. To facilitate this invasive behavior, the enzymatic breakdown of the extracellular matrix (ECM) is a prerequisite. Many human tumors are characterized by locally increased concentrations of matrix metalloproteinases (MMPs), enzymes that are able to degrade this ECM. A vast number of matrix metalloproteinase inhibitors (MMPIs) have been developed in recent years and after extensive preclinical testing, the results of the first clinical studies with several of these compounds have recently been presented. In this review we will describe some of the basic concepts of the degradation of the ECM, with special emphasis on the role of MMPs in the progression of cancer. Furthermore we will review the results of preclinical and clinical studies with MMPIs and discuss their future perspective.

Clinical Trials as Topic↗

Small cell lung cancer: state of the art and future perspectives.

Small cell lung cancer accounts for less than 20% of all lung cancer. The management of this distinct tumor entity differs from the more common non-small cell lung cancer. Primary prevention of smoking exposure remains the most important public health measure. Although small cell lung is an exquisitely chemosensitive disease it remains ultimately fatal for the great majority of patients. Combination chemotherapy regimens have improved response rate and survival of the last three decades. The combination of cisplatin and etoposide has been considered the standard therapy for over a decade. More intensive triplet combination chemotherapy and high-dose chemotherapy have shown improved response rates and survival. Early concomitant and accelerated radiotherapy improves survival in limited stage disease. This review summarizes the current state of the art and future perspectives in detection, staging and standard therapy of small cell lung cancer. Particular emphasis is given to the importance of concomitant and accelerated radiotherapy and consideration of dose-intensive combination chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗

Antiangiogenesis: current clinical data and future perspectives.

Neovascularization is a prerequisite for progressive growth of solid tumors and their metastases. This process is tightly regulated by a large number of proangiogenic and antiangiogenic factors such as VEGF, bFGF and matrix-metalloproteinases. The inhibition of angiogenesis is an innovative therapeutic approach and could represent a powerful adjunct to traditional therapy of malignant tumors. Preclinical trials have been very successful but in clinical studies meaningful response rates could only be shown in some cases. This might indicate the existence of different angiogenic phenotypes in humans. It seems that at present only a part of the interactions between the angiogenic cytokines are known. In addition, new receptor/ligand systems which regulate the neovascularization are being described. This article presents an overview of the most important angiogenically active substances, preclinical and clinical data, surrogate markers as well as future perspectives.

Angiogenesis Inhibitors↗

Animal cloning by nuclear transfer: state-of-the-art and future perspectives.

Model organisms are essential to study the genetic basis of human diseases. Transgenic mammalian models, especially genetic knock-out mice have catalysed the progress in this area. To continue the advancement, further sophisticated and refined models are crucially needed to study the genetic basis and manifestations of numerous human diseases. Coinciding with the start of the new era of post-genomic research, new tools for establishment of transgenesis, such as nuclear transfer and gene targeting in somatic cells, have become available, offering a unique opportunity for the generation of transgenic animal models. The new technology provides important tools for comparative functional genomics to promote the interpretation and increase the practical value of the data generated in numerous mouse models. This paper discusses the state-of-the-art of the nuclear replacement technology and presents future perspectives.

Animals↗

Adoptive immunotherapy with autologous macrophages: current status and future perspectives.

Adoptive immunotherapy is a treatment modality designed to correct a defective and/or insufficient host defense response to a malignant tumor. Recently, we have developed a large scale technology for the generation of tumor cytotoxic macrophages (MACs) from circulating precursor monocytes. These ex vivo matured and interferon-gamma-activated MACs were used for adoptive transfer in a total of 30 tumor patients by intravenous (n = 12), intraperitoneal (n = 11) and intrahepatic (n = 7) infusion. A biological response to autologous cell transfer was evident from low-grade fever, elevation of C-reactive protein, induction of the coagulation cascade and a rise in interleukin-6 in sera as well as in ascitic fluids. A clinical response was only seen upon intraperitoneal treatment and consisted of palliation of malignant ascites in 3 of 7 patients and in reduction of ascitic tumor markers (CEA, CA125). Future perspectives of MAC therapy in combination with macrophage colony-stimulating factor, bacterial endotoxins and synthetic derivatives as well as monoclonal antibodies against tumor-associated antigens are discussed. Furthermore, the ex vivo manipulation of the MAC system may offer the possibility to use these multifunctional, pleiotropic effector cells not only in malignancy but also for the therapy of complicated opportunistic infections and secondary bone marrow hypoplasia.

Cytotoxicity, Immunologic↗

Microvolt T-wave alternans: a review of techniques, interpretation, utility, clinical studies, and future perspectives.

Microvolt T-wave alternans (TWA) testing involves measuring variation in the morphology of the T-wave on an every other beat basis. The magnitude of the variation observed is typically on the order of a few microvolts. Thus in order to detect microvolt TWA, specialized recording and signal processing methods must be employed for reliable measurement. Additionally, microvolt TWA is not generally present at rest even in patients at risk of ventricular tachyarrhythmias and therefore exercise stress, pharmacologic stress, or atrial pacing must be utilized in order to elevate the heart rate. A positive MTWA test is one in which sustained TWA is present with an onset heart rate < or = 110 bpm. With current instrumentation, microvolt TWA represents an inexpensive, convenient non-invasive testing modality. Microvolt TWA has been evaluated prospectively in a variety of patient populations as a means of predicting occurrence of ventricular tachyarrhythmic events and its association with the genesis of ventricular arrhythmias has been demonstrated. Future role of microvolt TWA testing in noninvasive risk stratification is awaiting results of ongoing clinical trials. In this article, we tried to review the techniques, interpretation, indications, clinical studies, and future perspectives of microvolt TWA.

Anti-Arrhythmia Agents↗

Advanced mitigation strategies for acrylamide formation in foods: Mechanistic insights, emerging innovations, and future perspectives.

Acrylamide is a heat-induced contaminant formed predominantly in carbohydrate-rich foods during high-temperature processing, posing significant concerns due to its potential carcinogenic, neurotoxic, and genotoxic effects. This review critically examines the mechanisms of acrylamide formation, emphasizing the role of the Maillard reaction and key precursors such as asparagine and reducing sugars, along with the influence of processing conditions including temperature, time, pH, and moisture. Various mitigation strategies are comprehensively discussed, ranging from raw material selection and genetic approaches to enzymatic treatments such as asparaginase and the application of natural and chemical inhibitors. Advances in processing technologies, including optimization of conventional thermal methods and emerging non-thermal techniques such as cold plasma and ultrasound, are evaluated for their effectiveness. The review also highlights the role of food additives, functional ingredients, and fermentation in reducing acrylamide formation. Furthermore, recent developments in analytical techniques, including chromatographic methods, biosensors, and artificial intelligence-based predictive models, are explored for improved detection and control. Risk assessment, toxicological implications, and global regulatory frameworks are also examined. Finally, future perspectives focusing on genetic engineering, personalized nutrition, and digital technologies such as AI and blockchain are discussed to support sustainable and industry-applicable mitigation strategies.

Acrylamide↗

Brain cholinesterases: III. Future perspectives of AD research and clinical practice.

Alzheimer's disease (AD) is initially and primarily associated with the degeneration and alteration in the metabolism of cholinesterases (ChEs). The use of ChEs inhibitors to treat Alzheimer's condition, on the basis of the cholinergic hypothesis of the disease, is, therefore, without grounds. Most disturbing is the fact that the currently available anti-ChEs are designed to inhibit normal ChEs in the brain and throughout the body, but not the abnormal ones. Based on the acetylcholinesterase (AChE) deficiency theory, treatment should be designed to protect the cranial ChEs system from alteration and/or to help that system fight against degeneration through restoring its homeostatic action for brain structure and function instead. The overlap in the clinical, biochemical, molecular-cellular, and pathological alterations seen in patients with AD and individuals with many other brain disorders, which has bewildered many investigators, may now be explained by the shared underlying mismetabolism of brain ChEs. The abnormal metabolism of ChEs existing in asymptomatic subjects may indicate that the system is "at risk" and deserves serious attention. Future perspectives of ChEs research in vivo and in vitro in connection with AD and clinical diagnosis, prevention and treatment are proposed. Several potentially useful therapeutic and preventive means and pharmacological agents in this regard are identified and discussed, such as physical and intellectual stimulation, and a class of drugs including vitamin E, R-(-)-deprenyl (deprenyl, selegiline), acetyl L-carnitine, cytidine diphosphocholine (CDP-choline), centrophenoxine, L-phenylalanine, naloxone, galactose, and lithium, that have been proven to be able to stimulate AChE activity. Their working mechanisms may be through directly changing the configuration of AChE molecules and/or correcting micro- and overall environmental biological conditions for ChEs.

Acetylcarnitine↗

Nutrition and prevention of ischemic stroke: present knowledge, limitations and future perspectives.

Stroke, particularly ischemic stroke, has a major impact on public health due to its high incidence, prevalence and rate of subsequent disability in Italy as in most industrialised countries. Apart from age, many modifiable factors, such as hypertension, smoking, diabetes, dyslipidemia, obesity, physical inactivity, alcohol abuse and hyperhomocysteinemia, have been recognised as playing a role in the pathogenesis of this disease. While appropriate pharmacological therapy has proven effective in the prevention of stroke in particular categories of patients, most of the above mentioned predisposing conditions are amenable to be affected by nutrition. Unequivocal demonstration of a protective or adverse role of single foods and nutrients against the risk of stroke has been however difficult to achieve due to confounding by biological variability, methodological inadequacies in the assessment of individual nutritional habits and difficulty to carry out long-term randomised controlled trials in the nutritional area. Notwithstanding, in several cases, causal relationships could be inferred from case-control and cohort studies in the presence of plausible and reproducible associations, evidence of dose-dependent effects and consistency in the results of different studies. The aim of this paper was to review present knowledge and highlight limitations and future perspectives about the role of nutrition in the prevention of ischemic stroke.

Brain Ischemia↗

Bioartificial liver systems: current status and future perspective.

Because the liver is a multifunctional and a vital organ for survival, the management of acute liver failure requires the support of a huge number of metabolic functions performed by the organ. Many early detoxification-based artificial liver techniques failed to treat the patients owing to the inadequate support of the many essential hepatic functions. For this reason, a bioartificial liver (BAL) comprising of viable hepatocytes on a mechanical support is believed to more likely provide these essential functions than a purely mechanical device. From 1990, nine clinical studies of various BAL systems have been reported, most of which utilize a hollow fiber technology, and a much larger number of various BAL systems have been suggested to show an enhanced performance. Safety issues such as immunological reactions, zoonosis and tumorgenicity have been successfully addressed for regulatory approval, but a recent report from a large-scale, randomized, and controlled phase III trial of a leading BAL system (HepatAssist) failed to meet our expectation of efficacy in terms of the overall survival rate. In this paper, we review the current BAL systems actively studied and discuss critical issues such as the hepatocyte bioreactor configuration and the hepatocyte source. On the basis of the insights gained from previously developed BAL systems and the rapid progress in stem cell technology, the short-term and long-term future perspectives of BAL systems are suggested.

Animals↗

Apoptosis-detecting radioligands: current state of the art and future perspectives.

This review provides a critical and thorough overview of the radiopharmaceutical development and in vivo evaluation of all apoptosis-detecting radioligands that have emerged so far, along with their possible applications in nuclear medicine. The following SPECT and PET radioligands are discussed: all forms of halogenated Annexin V (i.e. (123)I-labelled, (124)I-labelled, (125)I-labelled, (18)F-labelled), (99m)Tc/(94m)Tc-labelled Annexin V derivatives using different chelators and co-ligands (i.e. BTAP, Hynic, iminothiolane, MAG(3), EDDA, EC, tricarbonyl, SDH) or direct (99m)Tc-labelling, (99m)Tc-labelled Annexin V mutants and (99m)Tc/(18)F-radiopeptide constructs (i.e. AFIM molecules), (111)In-DTPA-PEG-Annexin V, (11)C-Annexin V and (64)Cu-, (67)Ga- and (68)Ga-DOTA-Annexin V. In addition, the potential role and clinical relevance of anti-PS monoclonal antibodies and other alternative apoptosis markers are reviewed, including: anti-Annexin V monoclonal antibodies, radiolabelled caspase inhibitors and substrates and mitochondrial membrane permeability targeting radioligands. Nevertheless, major emphasis is placed on the group of Annexin V-based radioligands, in particular (99m)Tc-Hynic-Annexin V, since this molecule is by far the most extensively investigated and best-characterised apoptosis marker at present. Furthermore, the newly emerging imaging modalities for in vivo detection of programmed cell death, such as MRI, MRS, optical, bioluminescent and ultrasound imaging, are briefly described. Finally, some future perspectives are presented with the aim of promoting the development of potential new strategies in pursuit of the ideal cell death-detecting radioligand.

Animals↗

Present state and future perspectives of computer aided surgery in the field of ENT and skull base.

BACKGROUND: CAS technology has emerged in the last 10 years and is more and more used for surgery of the anterior and lateral skull base. Endoscopic and microscopic CAS systems are available. The endoscopic key hole or minimal invasive procedure is used increasingly not only for treatment of inflammatory disease, but also for tumour surgery. The integration of CAS systems into these procedures raises the level of their safety and efficiency. In addition, they allow the distance to the bone border on the CT slices to be previewed and measured. OBJECTIVE: Review of the present state of CAS systems, our own experience as a research centre and as users of the systems, demonstration of new navigational devices, microscope integration and a new registration procedure developed for the "Bernese" frameless optical navigation system (SurgiGATE ORL@1000, medivision, [Synthes, Stratec-medical], CH-4436 Oberdorf). MATERIAL AND METHODS: The optical CAS system with microscope integration (VM 900@1000, Möller-Wedel, Germany), new devices and new matching procedure; accuracy tests on a cadaver skull and on the patient's head. RESULTS: The practical accuracy on the cadaver skull with the pointer system has a mean average error of 0.79 mm, and the clinical accuracy is between 0.5 mm and 2 mm. CONCLUSION: CAS-microscope integration, new CAS technical devices and new noninvasive CAS-registration procedures support the surgeon in more minimally invasive surgical procedures of the paranasal sinuses and the skull base. Future perspectives will be discussed.

Humans↗