Our study consists in a series of clinical cases. It includes neurodegenerative diseases such as Alzheimer’s, Parkinson’s; stroke, small vessels diseases and cervical trauma; among other.
Symptoms of neuronal damage were present in all of the patients, these included: memory loss, cognitive impairment, hearing impairment (some cases with complete hearing loss), visual impairments (and loss), loss of balance, fine motor skills decline, loss of sphincter control, gait impairment, tremor, and muscular rigidity. All of which translated to incapacity in performing basic life activities (eating, getting dressed, doing dishes, bathing). These symptoms have been proven to ameliorate (and in some instances disappear) through the use of stem cells and regenerative therapy, increasing function and prolonging life expectancy with better life quality.
In this study neurotrophins along with BDNF were given directive or with signalling substances, such as:
• IGF 1 (and analogs)
• P21 gene stimulator: which targets the entirety of the nervous system (both peripheral and
central)
• Selank and Semax: peptides that improve the cerebral vascular system and stimulate the
production of neurons and reduce stress/inflammation in the glial system
• Growth Hormone: influences neuronal development while reducing inflammation
. Different cytokines for improve immunologic system; reduce inflammation and fibrosis.
• Epithelia: a peptide that improves the hypothalamus-pituitary axis improving both nervous and
endocrine system
Signalling and activation of diverse types of Stem cells for diverse chronic diseases is becoming today the treatment gold standard in regenerative medicine. This is being used alongside with genetic activation of specific genes that have been silenced due to oxidative stress, mutations, external factors, and etcetera.
It is to be noticed that certain carrier proteins and their affinity for both nuclear and mitochondrial receptors have an important role as well in regenerative medicine. Focus is being targeted to the glutamate (especially NMDA), glycine, serotoninergic, dopaminergic; gabaergic and cholinergic receptors when it comes to the treatment of neurodegenerative diseases. This is a very promising source of treatment and even cure of certain neurodegenerative conditions; moreover, it is noticeable that these novel therapies also have a positive impact almost of these conditions.

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The autologous blood and cell therapies have become increasingly popular in the last decade due to the great results in management of musculoskeletal problems and disease, in particular in sport injuries and expected to multiply in the near future, The self-healing power of the body are used in side effect-free treatment and promoted an accelerating healing process and fast pain-free recovery. All biologics are characterized by their regenerative and signalling capacities. Goal of autologous biologics is to introduce the cells directly to the site of tissue injury/repair to augment healing. There are three essential factors for tissue healing that result in  revascularization. The stem cells should contain the heterogenous mix of cells and signaling factors that orchestrates tissue healing. Not all systems are created equal; consistency is key.To enhance such treatment it should be individualised and taking into account the individual circumstances and environment and the team work effectiveness. A summarised plan and protocol for beginners on how to master the work in Regenerative therapy is proposed and sharing  my experience about the effectiveness of regenerative therapy in the world of Orthopaedics.

One of the most common problems in patients with diabetes mellitus is development of symptom is diabetic foot ulcer. Until now, various methods have been used to treat the developed foot problem with some great or less great success. In our research we used modified method by combing various methods to reach better treatment of the patients. Namely, in patients with developed diabetic foot ulcer we used fibrin glue with platelet rich plasma (Regenlab BCT2, Switzerland) and stem cells obtained by using kit RegenKit Extra cell BMC (Regenlab, Switzerland) obtained from each patient. On the other hand, some of the patients were treated with classic treatment without using named reagents. Obtained results showed that in patients treated with fibrin glue PRP and stem cells results with great recovery and better condition compared to the patients treated with classical method. The reason for this rapid recovery might be huge among of growth factors released from PRP as well as combination with different reeling factors from stells. Further research should be provided to prove the noticed difference as well to evaluate the factors involved in wound healing.

Introduction. Homeopathic remedies are prepared according to special technology, used in small doses, and the advantage of their use is that they make it possible to eliminate not only the symptoms of diseases, but the causes of diseases as well resulting in almost complete recovery of patient. The main effect of homeopathic medicines is aimed at restoring adaptation mechanisms boosting the immune system, the final effect is realized not only via immune system, but endocrine, cardiovascular, nervous systems as well.
Purpose of study. The aim of the present study was to prepare homeopathic sugar granules and drops based on licorice (Glycyrrhiza glabra) as well as other medicinal plants used for the treatment of respiratory tract diseases in children and the elderly and for strengthening the immune system.
Study design. To obtain the homeopathic remedy first, the extract from fresh collected licorice and appropriate medicinal plants using 70% ethyl alcohol was prepared. The final phytopreparation was prepared in the form of drops and granules in 6D dilution. For this, the freshly harvested roots and herbs were crushed to obtain the mushy mass, poured with 70% ethyl alcohol in a ratio of 1:5, kept for 30 minutes, squeezed well. The resulting parent extract was potentiated with demineralized water to a pure potency of 6D. Then, depending on the target form, the resulting extract was added to the sugar granules, or to 25% ethyl alcohol to obtain the drop form.
Discussion. The benefits of the newly developed homeopathic composition compared to known ones are as follows: this composition of herbal origin exhibits a pronounced immunomodulatory effect and is harmless to newborns. Lack of contraindications and side effects, convenience of admission for patients of all age groups and the possibility of using in combination with allopathic drugs makes it an indispensable tool for treatment diseases of the upper respiratory tract of an inflammatory nature.
Conclusion. The essence of the developed invention is that treatment with the obtained remedy in children and the elderly leads to improvement of the general condition and relief of cough, increases immunity and has an effect in the treatment of the upper respiratory tract diseases without creating an allergy background.

Humans, animals and plants are the main living reigns on planet earth. Their common factor is stem cells.For more than 3 decades humans Stem Cells has been researched, and used for regenerative medicine purposes with excellent results. Because of the controversy around embryonic stemcells, researchers have been looking for alternatives.They were lucky to discover that plants have stemcells hiden in their meristem. A wide range of biotechnologies has been developed to extract and cultivate plant based stemcells for healthcare, cosmetic industry with very promising and extravagant success.It is known and proven that plants are very resistant to all kind of difficulties and pressure in their life time. The plant resistance is also called Plant Intelligence.Plant Intelligence generally is tributed to 6 different phytochemicals groups manufactured by plants: Flavonoids, Carotenoids, Polyphenols, Organic sulfides, Phytoestrogens and remaining phytochemicals such as ginger, curcumin, chlorophyll, limonin, etc.Researches have confirmed that phytochemicals containing diverse biological actives and can help humans in various ways, including anti-oxidation, tumor inhibition, anti-inflammation, cardiovascular improvement, microorganism inhibition, immunity regulation, whitening, and wrinkle elimination, etc., and can prevent many chronic diseases.In this discussion we will share some plant based stemcell products and the mindblowing  testimonials of former sick people that consumed them.

Statement of the Problem: Obesity arises from an imbalance between energy intake and energy expenditure. This study aims to determine the mechanism of cooperation and harmonization between energy homeostasis and tissue homeostasis to maintain a stable body weight variable orchestrated by the immune system.
Methodology and Theoretical Orientation : Two groups of local adult male rabbits (n = 16) were fed a high calorie diet: HCD (4538 Kcal/kg DM) and a finishing diet (FD: 3964 Kcal/kg DM). After fifteen weeks of feeding, the animals were sacrificed according to Algerian legislation. Blood glucose, insulin, leptin, total cholesterol, high-densitylipoprotein (HDL), low-densitylipoprotein (LDL) and triglyceride were determined. The heart, the kidneys, visceral adipose tissue (VAT) from the abdominal cavity, mesentery and retroperitoneal fat, liver, adrenals and testis were dissected, removed and fixed in 4% formalin. These removed organs were divided between histology (for structural and morphometric analysis cells) and immunohistochemistry (to determine apoptosis and cell proliferation) by analysis of CD45 and KI67 expression. The body weight, a total weight (g tissue) and relative weights (g tissue/body weight) for VAT, testis and adrenals were then estimated. The Image J program (Image J, Version 1.52v) using for quantitative analyses of digital images whereas R programming language version (4.1.0) was used for statistical analysis.
Findings: It has been shown that HCD-received rabbits have developed visceral obesity, dyslipidemia and insulin resistance (IR) by dramatically increasing body weight, visceral fat tissue, testis and adrenal weight. HCD also causes the process of inflammatory fibrosis in the adrenal gland and adipose tissue, also a microvesicular steatosis in liver, hyperplasia and hypertrophy of adipose tissue, testis and adrenal gland with angiogenesis in heart. The surplus calorie in fed rabbits caused them too, disorganization of structural architecture of testis and adrenal gland.In our study, we found that the CD45 antibody could be immunoreactived with the adipose tissues in the membrane significantly in HCD fed animals. Thus, in this practice, we determined if Ki-67 and CD45 expression would be useful for calculating apoptosis and cell proliferation as well as a morphometric analysis of cells.
Conclusions : Tissue remodeling either by hypertrophy or hyperplasia compensates for the energy imbalance as a defense mechanism against this imbalance. This study gives a new concept to obesity so th calorie in excess of the body’s need, represented an stimulis, whereby the system immune and Stem cell progeny of some organs colaboreted to maintain a balance : energy homeostasis- tissue homeostasis.

During radiotherapy, the radiation beam can affect healthy tissues in the field of irradiation, even if it specifically targets the tumor, causing sequelae in 10% of patients that can occur up to 20 years after treatment. In the abdominal-pelvic area, this results in severe pain and extremely disabling functional disorders of the bladder and bowel. Current treatments are mainly symptomatic, and some patients do not respond.

For several years, Institute de Radioprotection ET Surete Nuclearie has been conducting research on cell therapy strategies using Mesenchymal Stromal Cells to repair radiation-damaged tissue. This experimental research, which is currently being carried out on different animal models, indicates that in the abdominal-pelvic area, Mesenchymal Stromal Cells stimulate the repair process after irradiation. They have thus made it possible to offer this treatment in a compassionate setting to human victims of the radiotherapy accident that occurred at the Jean Monnet Hospital in Epinal (Vosges, France). Four patients suffering from severe pelvic side effects due to excessive radiation dose after conformal radiotherapy for prostate adenocarcinoma received intravenous injections of allogeneic mesenchymal stromal cells.

For treated patients, mesenchymal Stromal Cell therapy was effective on pain, diarrhea, hemorrhage, inflammation, fibrosis and limited fistulization. No toxicity was observed. We are now starting inclusion in a clinical research protocol of phase 2, for patients with post-radiation abdominal and pelvic complications who have not seen their symptoms improve after conventional treatments (NCT 02814864, PRISME). Patients included in this trial will receive injections of allogeneic Mesenchymal Stromal Cell (from intra-family donors) and will be followed for 12 months at Hospital St-Antoine (Paris, France).

At the end of this period, if the efficacy of the treatment is proven, a phase III trial including a larger number of patients over a longer period will be used to confirm the therapeutic properties of this treatment.

Background: α-thalassemia is an inherited blood disorder caused by mutations in α-globin genes (HBA1 and HBA2) resulting in the reduction of α-globin chains, the subunit along with β-globin chain constituting adult hemoglobin (α₂β₂). Severe α-thalassemia arises with α-globin expression levels of <30% or less, and α/β-globin ratio of <0.2, caused by defects in or absence of three or all four α-globin genes. Treatment for survival entails lifelong, biweekly blood transfusions with daily chelation therapy. While these therapies enable patients to live into mid- to late-adulthood, they continue to engender serious clinical manifestations.

To answer this clinical need, our laboratory has developed a stem cell gene therapy in which functional copies of α-globin gene integrate into the genome of patient’s hematopoietic and progenitor stem cell (HSPC) by lentiviral vectors (LVs) to normalize the globin chain imbalance and restore hemoglobin function. The design of our α-globin LVs (AGLVs) is based on GLOBE β-globin LV utilized in a clinical trial for β-thalassemia (NCT02453477), which has achieved transfusion independence in patients with transfusion-dependence β-thalassemia major. To target excess infective erythropoiesis and hemoglobin restoration, we have constructed a series of short proviral length AGLVs for optimized titer production, HSPC infectivity, and gene expression.
Research: Twelve AGLVs varying in gene and regulatory element compositions were constructed and assessed for raw titer yields and characterized for gene transfer efficiency, mRNA expression and hemoglobin production in a α-globin knockout (KO) human erythroid cell line. Successfully, all AGLVs confer high raw titers ~ 1e7 TU/mL and were able to yield adult hemoglobin. We identified two optimal AGLVs for further characterization in human primary HSPCs: 1) Alpha2 LV for yielding highest raw titers and gene transfer efficiency, and 2) LCR-Globe LV for producing the most α-globin mRNA. Both Alpha2 and LCR-Globe LVs harbor HBA2, are regulated by the β-globin promoter and enhanced by the core or large β-LCR enhancer region, respectively. To assess candidate AGLVs in human HSPCs, AGLVs were tagged at the transcription level to enable identification and quantification of vector-derived α-globin mRNA proceeding HSPCs transduction and erythroid differentiation. Alpha2 demonstrated optimum CD34⁺ infectivity and gene transfer, and LCR-Globe expressed a high ~30% of α-globin mRNA per total β-globin per vector copy number (VCN), achieving levels of one endogenous α-globin gene (~25% per total β-globin).We then assessed one of these vectors in Alpha Thalassemia Major (ATM) patient HPSCs – lacking all four α-globin genes. We successfully demonstrated that a low average of copies per cell (~2) restored adult hemoglobin formation by 50%, which was determined by measuring α-globin chains (produced by the introduced α-globin gene) to other endogenous β-globin chains. (To note, two endogenous α-globin genes, or 50% gene expression, result in asymptomatic cases of α-thalassemia in most patients). We further showed that transduced cells are similar to healthy RBCs; round, pale enucleated RBCs, unlike the untransduced patient RBCs which contained more nucleated cells (sign of ineffective RBC maturation). These preliminary patient cell results are promising and will be repeated with further morphologic and gene expression measurements.Based on these positive results, we are confidently moving forward with animal studies. The selected mouse model contains a mild form of α-thalassemia caused by a deletion of two α-globin genes and present human-like symptoms of AT, such as anemia and an enlarged spleen. These vectors have been converted to murine-carrying α-globin., We are currently assessing these newly converted murine vectors in an erythroid murine cell line, containing a large deletion of all four α-globin genes. Overall, these animal assays will determine the candidate clinical vector, and underpin the potential of this promising stem cell gene therapy as a curative approach for patients suffering from severe α-thalassemia.

Benefits to stem cell science: This research project will pave the way for the first development of a potential curative approach for α-thalassemia using the patient’s own hematopoietic stem cells. Moreover, these assays will provide further characterization of uncorrected and corrected RBC development in α-thalassemia patients, thereby shedding light on the characterization of the disease. Fundamentally, this research project will deepen our understanding and expertise on the usage of lentiviral vectors for stem cell gene addition treatments for immune system and blood disorders, such as β-thalassemia and sickle cell disease.

Chronic diseases confer tissue and organ damage that reduce quality of life and are widely refractory to therapy. Degenerative diseases are strongly associated with chronic inflammation in patients who are candidates for regenerative medicine treatments. Although stem cells hold promise for treating degenerative diseases, the regenerative capacity of stem cells is influenced by regulatory networks guided by local immune responses to tissue damage. Recent research has turned to how cellular and signaling components of the local stromal microenvironment (the 'soil' to the stem cells' seed), such as local inflammatory reactions, contribute to successful tissue regeneration. For this reason, it is important to consider that all measures cabale of decreasing the degree of inflammation in the body are appropriate for the preparation of the patient: sleep, gut microbiome,    environmental toxins, hormone balance, electromagnetic fields and other illness conditions, to pose the patient in a balanced position for the regenerative procedures. Application of “preparing the soil” concepts to regenerative medicine strengthens prospects for developing cell-based therapies or for promotion of endogenous repair.

The increasing burden of musculoskeletal disorders combined with the high utilization of opiates, NSAIDs and the relatively limited ability of traditional approaches to satisfactorily address many of the conditions that causes osteoarticular pain has spurred an increased interest in alternative treatments such as regenerative medicine therapies. Osteoarticular pain is a critical health, social, and economic issue in modern societies. Evidence is growing to support the use of orthobiologic injection treatments. Regenerative injection-based therapy has established itself as a therapeutic option for the management of osteoarthritis pain for most orthopedic conditions using platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), bone marrow aspirate (BMA) and mesenchymal stem cell from fat (biofat). This conference will show the results of this therapies in a sample of Brazilian patients with low back pain involving the muscle-ligament-facet-discal  complex, and other orthopedic degenerative conditions and osteoarthritis of joints.The increasing burden of musculoskeletal disorders combined with the high utilization of opiates, NSAIDs and the relatively limited ability of traditional approaches to satisfactorily address many of the conditions that causes osteoarticular pain has spurred an increased interest in alternative treatments such as regenerative medicine therapies. Osteoarticular pain is a critical health, social, and economic issue in modern societies. Evidence is growing to support the use of orthobiologic injection treatments. Regenerative injection-based therapy has established itself as a therapeutic option for the management of osteoarthritis pain for most orthopedic conditions using platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), bone marrow aspirate (BMA) and mesenchymal stem cell from fat (biofat). This conference will show the results of this therapies in a sample of Brazilian patients with low back pain involving the muscle-ligament-facet-discal  complex, and other orthopedic degenerative conditions and osteoarthritis of joints.

INTRODUCTION: Fat graft enriched with adipose-derived stem cells (FG-e-ASCs) has been utilized in outcomes of radiotherapy after mastectomy, and breast soft tissue defects. The scientific results using FG-e-ASCs in breast augmentation and breast reconstruction have been reported.
METHODS: A total of 46 patients affected by breast hypoplasia (SG-1) were treated with FG-e-ASCs, comparing results with those of a CG-1 (n = 30) treated with fat graft not enriched with adipose-derived stem cells (FG-ne-ASCs). 121 patients affected by the outcomes of breast oncoplastic surgery (SG-2) were treated with FG-e-ASCs, comparing the results with the CG-2 (n = 50) treated with FG-ne-ASCs. The preoperative evaluation included a complete clinical evaluation, photographic assessment, magnetic resonance imaging (MRI) of the soft tissue, ultrasound (US), and mammography (MG). Biopsy was performed only in SG-2. Postoperative follow-up took place at 1, 3, 7, 12, 24, 36, and 48 weeks, and then annually. 
RESULTS: SG-1 patients, treated with FG-e-ASCs showed 58% maintenance of the contour restoring and of 3-dimensional (3D) volume after 3 years compared with the patients of the CG-1 treated with FG-ne-ASCs, who showed only 29% maintenance. In 67.4% (n = 31) of breast augmentation treated with FG-e-ASCs, we observed a restoration of the breast contour and an increase of 10.3 mm in the 3D volume after 36 months, which was observed in only 20.0% (n = 6) of patients in the CG treated with FG-ne-ASCs. Volumetric persistence in the SG-1 was higher than that in the CG-1 (P < .0001 SG vs. CG).  In 72.8% (SG-2 n = 88) of breast reconstruction treated with FG-e-ASCs, we observed a restoration of the breast contour and an increase of 12.8 mm in the three-dimensional volume after 12 weeks, which was only observed in 27,3% (n = 33) of CG-2. Volumetric persistence in the SG-2 was higher (70.8%) than that in the CG-2 (41.4%) (p < 0.0001 vs. control group).

CONCLUSION: The use of FG-e-ASCs was safe and effective in patients of SG-1 and SG-2. 

Regenerative medicine aims to find new therapeutic options for chronic-degenerative diseases, like knee osteoarthritis, in order to reduce pain and improve function. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) have been candidates for regenerative therapies for knee osteoarthritis.
Materials and Methods:
 We have investigated three Brazilian woman presenting with pain, edema and functional joint limitation on the knees. The mean age was 75 years old and it ranges from 70 to 79 years. MRI analysis revealed findings of grade III osteoarthritis of the both knee in two patients and in the left knee of the oldest patient. MRI also shows the presence of osteophytes, signals of joint degeneration and osteonecrosis of the medial condyle and plateau more advanced in the oldest patient.
Adipose tissue of each patient was aspirated and processed under GMP conditions in a cell culture facility for 30 days. MSCs were purified and expanded until the forth passage, when the cells were characterized by confocal microscopy, FACS analysis and differentiation assays into chondrocytes, osteocytes and adipocytes. Absence of chromosomal aberrations was verified by G-band karyotype. The cells were dissociated, resuspended in saline solution containing 20% human serum albumin and placed in syringes.Under local anesthesia, MSCs were intra-articularly injected into the affected knees. The patients were also administered with autologous activated platelet-rich plasma, intra-articularly, on the day of the lipoaspiration and on the day of MSC transplantation. The second administration of autologous activated platelet-rich plasma was performed five minutes before the MSC transplantation.
Results and Conclusions:
The patients evolved with amelioration of local pain, edema regression and increased joint mobility. MRI analysis demonstrated attenuation of the signs of osteoarthritis and prominent reduction of the images of osteonecrosis. Association of intra-articular transplantation of MSCs and administration of PRP may be an effective approach to treat knee osteoarthritis.    

A complete spinal cord injury (SCI) is the complete sensory and motor loss below the site of spinal cord injury following acute or chronic destruction, compression, or ischemia of the spinal cord. It constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of our combinatorial biologics based in the combination of a unique polypeptide (Bioquantine®) and Umbilical Cord Mesenchymal Stem Cells (UCMSCs) represents one of the most important and promising and now safe and tested strategy to stimulate the neuroregeneration. This combinatorial method attract, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. In this review, the therapeutic role of UCMSCs is discussed, together with their properties, application, limitations, and future perspectives. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. The current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of UCMSCs that can be used in the treatment of SCI. Our evidence and science based method (as we previously demonstrated with a patient 2 years ago) is showing a promising alternative on the ASIA-A classification SCI. Added to it, we utilized an improved delivery method (making it ambulatory) for the in situ application of subdural UCMSCs and a unique polypeptide (Bioquantine^®). Thereafter we proceeded with the intrathecal application of an advanced neurostimulator biomedical system obtaining improved results and faster clinical recovery after only 5 weeks of the started translational protocol.

Statement of the Problem: COVID-19 infection and long-term COVID-19 syndrome remain to burden healthcare systems and cause significant morbidity and mortality. Novel molecular targets related with the dynamics of pathogenesis of COVID-19 disease, and the use of mesenchymal stem cells (MSCs) in cell therapies have been methods that deserve attention and are frequently investigated [1]. In fact, MSCs are effective and safe alternatives for treating cytokine storm and acute inflammation, as there are no reductive medications to improve pulmonary fibrosis, acute respiratory distress syndrome (ARDS) and post complications of immune unregulation [2]. Methodology and Theoretical Orientation: Eight severe/critically severe COVID-19 patients who were unable to respond to the treatment algorithms suggested by the Turkish COVID-19 Scientific Committee had MSC transplantation between April 1 and May 4, 2020 [3]. About a year later, we also performed UC-MSC transplantation in 210 patients with severe or critically severe COVID-19, and we assessed the clinical outcomes.
Findings: According to the findings, stem cell therapy has the potential to reduce mortality and morbidity [4]. Stem cells can enhance lung function and diminish symptoms by lowering inflammation, thus significantly lowers COVID-19 patients' mortality and morbidity, specifies a recent meta-analysis study that included our findings as data from Turkey [5]. Another meta-analysis study that included our subsequent investigation concluded that MSC transplantation is safe and beneficial for patients with severe COVID-19, which is consistent with our findings [6]. Additionally, it can be indicated that MSCs are quite beneficial in improving the clinical signs of COVID-19 infection and lowering systemic complications significantly due to their immunomodulation and regenerative properties.
Conclusion & Significance: Since it has a significant effect in reducing pulmonary fibrosis and enhancing lung function, it can be suggested that emerging treatment for COVID-19 is mesenchymal stem cell therapy. Studies conducted in this context point to promising results. However, further prospective studies are needed to confirm the results and establish a uniform protocol.