Best Route Of Administration Research Articles

Stem cell-derived exosomes for ischemic stroke: a conventional and network meta-analysis based on animal models.

We aimed to evaluate the efficacy of stem cell-derived exosomes for treating ischemic stroke and to screen for the optimal administration strategy. We searched PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases for relevant studies published from their inception to 31 December 2023. Conventional and network meta-analyses of the routes of administration, types, and immune compatibility of stem cell-derived exosomes were performed using the cerebral infarct volume (%) and modified neurological severity score (mNSS) as outcome indicators. A total of 38 randomized controlled animal experiments were included. Conventional meta-analysis showed that compared with the negative control group: intravenous administration significantly reduced the cerebral infarct volume (%) and mNSS; intranasal administration significantly reduced the cerebral infarct volume (%); and intracerebral administration significantly reduced the mNSS. Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos), bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), dental pulp stem cell-derived exosomes (DPSC-Exos) and neural stem cell-derived exosomes (NSC-Exos) significantly reduced the cerebral infarct volume (%) and mNSS; Endothelial progenitor cell-derived exosomes (EPC-Exos), embryonic stem cell-derived exosomes (ESC-Exos), induced pluripotent stem cell-derived exosomes (iPSC-Exos) and neural progenitor cell-derived exosomes (NPC-Exos) significantly reduced the cerebral infarct volume (%); Umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) significantly reduced the mNSS; and there was no significant difference between urogenital stem cell-derived exosomes (USC-Exos) and negative controls. Engineered modified exosomes had better efficacy than unmodified exosomes. Both allogeneic and xenogeneic stem cell-derived exosomes significantly reduced the cerebral infarct volume (%) and the mNSS. The network meta-analysis showed that intravenous administration was the best route of administration for reducing the cerebral infarct volume (%) and mNSS. Among the 10 types of stem cell-derived exosomes that were administered intravenously, BMSC-Exos were the best type for reducing the cerebral infarct volume (%) and the mNSS. Allogeneic exosomes had the best efficacy in reducing the cerebral infarct volume (%), whereas xenogeneic stem cell-derived exosomes had the best efficacy in reducing the mNSS. This meta-analysis, by integrating the available evidence, revealed that intravenous administration is the best route of administration, that BMSC-Exos are the best exosome type, that allogeneic exosomes have the best efficacy in reducing the cerebral infarct volume (%), and that xenogeneic exosomes have the best efficacy in reducing mNSS, which can provide options for preclinical studies. In the future, more high-quality randomized controlled animal experiments, especially direct comparative evidence, are needed to determine the optimal administration strategy for stem cell-derived exosomes for ischemic stroke. https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42024497333, PROSPERO, CRD42024497333.

Dexmedetomidine for agitation in dementia: Current data and future direction.

The incidence and prevalence of dementia, and thus dementia-related behavioral and psychological symptoms, are increasing significantly. Currently, there are limited safe and efficacious options for treating these symptoms. Dexmedetomidine has been used for agitation related to delirium and showed significant benefit in prior studies. This raises the question whether dexmedetomidine could also provide a safe and effective treatment for BPSD, including agitation related to dementia. Our team searched PubMed, Cochrane Database, and Ovid with the terms dexmedetomidine and dementia. Only studies published in English language journals, or with official English language translations, and human studies were included. All reports of dexmedetomidine for dementia were included regardless of study type. No completed studies on dexmedetomidine for agitation in dementia were identified. The TRANQUILITY study is in progress, although results are yet to be published. Dexmedetomidine has shown benefit for hospital delirium and for agitation in schizophrenia and bipolar disorder. However, there are no completed studies published on dexmedetomidine for agitation in dementia. Controlled studies with larger sample sizes are needed to assess the efficacy, safety, and the best route of administration for this drug in managing BPSD including agitation.

Comparative efficacy and safety of different anti-VEGF agents combined with different delivery methods for neovascular glaucoma: a systematic review and Bayesian network meta-analysis

ObjectiveTo compare the efficacy and safety of different anti-vascular endothelial growth factor (VEGF) agents combined with different delivery methods for neovascular glaucoma (NVG).DesignSystematic review and Bayesian network meta-analysis (NMA).Data sourcesPubMed,...

How Thymoquinone from Nigella sativa Accelerates Wound Healing through Multiple Mechanisms and Targets.

Wound healing is a multifaceted process necessitating the collaboration of numerous elements to mend damaged tissue. Plant and animal-derived natural compounds have been utilized for wound treatment over the centuries, with many scientific investigations examining these compounds. Those with antioxidant, anti-inflammatory, and antibacterial properties are particularly noteworthy, as they target various wound-healing stages to expedite recovery. Thymoquinone, derived from Nigella sativa (N. sativa)-a medicinal herb with a long history of use in traditional medicine systems such as Unani, Ayurveda, Chinese, and Greco-Arabic and Islamic medicine-has demonstrated a range of therapeutic properties. Thymoquinone exhibits antimicrobial, anti-inflammatory, and antineoplastic activities, positioning it as a potential remedy for skin pathologies. This review examines recent research on how thymoquinone accelerates wound healing and the mechanisms behind its effectiveness. We carried out a comprehensive review of literature and electronic databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus. Our aim was to gather relevant papers published between 2015 and August 2023. The main criteria for inclusion were that the articles had to be peer reviewed, original, written in English, and discuss the wound-healing parameters of thymoquinone in wound repair. Our review focused on the effects of thymoquinone on the cellular and molecular mechanisms involved in wound healing. We also examined the role of cytokines, signal transduction cascades, and clinical trials. We found sufficient evidence to support the effectiveness of thymoquinone in promoting wound healing. However, there is no consensus on the most effective concentrations of these substances. It is therefore essential to determine the optimal treatment doses and the best route of administration. Further research is also needed to investigate potential side effects and the performance of thymoquinone in clinical trials.

Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs.

Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demyelination and motor and cognitive impairments due to deficiencies of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing the AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intravenously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis: Evidence and uncertainties.

Liver cirrhosis is commonly associated with nutritional alterations, reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis. Nutritional disturbances are associated with a worse prognosis and increased risk of complication. Serum levels of branched-chain amino acids (BCAAs) are decreased in patients with liver cirrhosis. The imbalance of amino acids levels has been suggested to be associated with the development of complications, such as hepatic encephalopathy and sarcopenia, and to affect the clinical presentation and prognosis of these patients. Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis, but uncertainties remain about the real efficacy, the best route of administration, and dosage.

Cell-based therapeutic strategies for treatment of spinocerebellar ataxias: an update.

Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion, which encodes a long glutamine tract (polyglutamine) in the respective wild-type protein causing misfolding and protein aggregation. Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation, mitochondrial dysfunction, decreased proteasomal activity, and autophagy impairment. Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system. Spinocerebellar ataxias are mostly characterized by progressive ataxia, speech and swallowing problems, loss of coordination and gait deficits. Over the past decade, efforts have been made to ameliorate disease symptoms in patients, yet no cure is available. Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration. So far, pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation, including animal models of spinocerebellar ataxia types 1, 2, and 3. However, contrasting results can be found in the literature, depending on the animal model, cell type, and route of administration used. Nonetheless, clinical trials using cellular implants into degenerated brain regions have already been applied, with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions, reconstructing the affected neural network. Meanwhile, the question of how feasible it is to continue such treatments remains unanswered, with long-lasting effects being still unknown. To establish the value of these advanced therapeutic tools, it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease. Further studies are needed to determine the best route of administration, without neglecting the possible risks of repetitive transplantation that these approaches so far appear to demand. Despite the challenges ahead of us, cell-transplantation therapies are reported to have transient but beneficial outcomes in spinocerebellar ataxias, which encourages efforts towards their improvement in the future.

Comparative Immunogenic Response of Live Vaccine of Lasota and Mukteswar Strains of Newcastle Disease Virus by Different Routes of Inoculation in Layer Chicken

Newcastle disease (ND) has been one of the great challenges to Poultry in Pakistan and dealt with vaccination. Mortality and morbidity that are associated with it are economically significant. Two vaccines produced against Newcastle disease virus are Live ND-LaSota and ND Mukteswar vaccines and their immunogenic effects in backyard poultry. For that purpose, a total 130 of 6-8 weeks old layer cockerels were inoculated with both vaccines by different routes including Ocular, drinking water and Injection and serum samples were collected at 14, 21 and 35 days’ post inoculation were analyzed by Heamaglutination inhibition test for antibody titers. The best route of administration for ND-LaSota was observed by ocular drops and ND- Mukteswar through injection. So it was concluded that both the vaccines needed booster doses in 4th to 5th week of primary inoculation. ND-LaSota vaccine was found to be best for primary induction.

Abomasal ulcers: Do ranitidine or omeprazole prevent phenylbutazone-induced lesions in sheep?

Treatment and prevention of gastric ulcers are well known in monogastric animals; however, there are uncertainties about the preventive effects of acid-reducer drugs, their dosages and the best route of administration to ruminants. The object of this research was to test the preventive actions of ranitidine and omeprazole on abomasal ulcer development in sheep treated with a high dosage of non-steroidal anti-inflammatory drug. Eight healthy adult sheep with abomasal cannula were distributed in two contemporary and balanced 4 × 4 Latin squares (eight animals per group). For seven days, animals in the control group received high doses of phenylbutazone (4.4 mg/kg, every 12 h) while the treated groups received the same high doses of phenylbutazone plus an acid-reducer drug, namely 2 mg/kg of intravenous ranitidine every 12 h; 0.4 mg/kg of intravenous omeprazole; 4 mg/kg of oral paste omeprazole, both once a day. Intravenous omeprazole caused phlebitis, increasing serum fibrinogen content, and 75 % of the treated animals were diagnosed with type 1a ulcers in abomasal mucosa. Oral omeprazole showed no adverse effects, but was not effective in preventing type 1a ulcer in 50 % of animals, which was the same amount as diagnosed in control group. Despite of a minor heart rate increase, ranitidine treated animals showed only 37.5 % of abomasal injuries. Based on clinical findings, intravenous ranitidine is apparently better than omeprazole in prevention of abomasal ulcers, but another kind of experimental design comparing group by group is required and strongly recommended to ensure the beneficial effect of ranitidine.

Enhanced tumor control with a combination of APG-157 and immune checkpoint inhibitors for head and neck cancer.

2652 Background: Natural botanical drugs containing flavonoids are under clinical investigation for the treatment of malignancies. A phase I clinical study for patients with locally advanced head and neck cancer with a new class of botanical drug APG-157 showed excellent tolerability, systemic absorption via sublingual administration, and enhanced immune cell infiltration into the tumor microenvironment and suppression of T cell inhibitory inflammatory cytokine production. We sought to evaluate the efficacy of tumor control for the combination of APG-157 and checkpoint blockade immunotherapy using a head and neck cancer mouse model. Methods: SCCVII (HPV-) and MEER (HPV+) head and neck cancer murine cell line models were utilized in in vivo tumor growth study. After optimization for route and cell number, we measured tumor growth after treating mice with following groups: i) control, ii) APG-157, iii) anti-PD-1, iv) anti-CTLA-4, v) APG-157 + anti-PD-1, vi) APG-157 + anti-CTLA-4, vii) anti-PD-1 and anti-CTLA-4, viii) APG-157 + anti-PD-1 + anti-CTLA-4. Tumors were collected after 2 injections of immune checkpoint inhibitors and characterized for immunophenotype by multi-color flow cytometry, immunohistochemistry, and RNA-sequence analysis. Fecal microbiome was analyzed by 16S rRNA sequence for SCCVII model to assess the impact of APG-157 on the microbiome as we observed the shift of oral microbiome species in the human trial. Results: We confirmed by serum concentration of APG-157 metabolites that the best route of administration is via oral route by mixing with APG-157 with mouse chow. Tumor growth optimization experiments determined that 100,000 cells of SCCVII is the ideal number of cells to inject and day 5-6 is the time to initiate treatment. Among 8 treatment groups, APG-157 + anti-CTLA-4 demonstrated best tumor control (p = 0.0065 compared to control), followed by anti-PD-1 + anti-CTLA-4 treatment group (p = 0.48 compared to control). The immunophenotype assessment by flow cytometry showed over 30% of CD8+ T cell in APG-157 + anti-CTLA-4 group compared to 4-5% of CD8+ T cell for the control group. GSEA analysis from the SCCVII tumors revealed that APG-157 + anti-CTLA-4 group showed an enriched set of genes for inflammatory response, apoptotic signaling pathways. The fecal microbiome analysis showed a substantial difference of lactobacillus genus among groups, highest in the group of APG-157 + anti-CTLA-4 treatment group. The MEER model (HPV positive) tested with same immunotherapy as single or in combination with APG-157 did not grow the tumor, thus we were unable to collect the tumor for immunophenotyping and other studies. Conclusions: These study results indicate that APG-157 is able to modulate the immune system and fecal microbial species that could potentially lead to improved anti-tumor immunity and warrants further studies to define mechanism and the potential for human clinical trial.

Regenerative Effects of Locally or Intra-Arterially Administered BMSCs on the Thin Endometrium.

Stem cell–based therapy plays a pivotal role in the regeneration of damaged endometrium. Previous studies have demonstrated the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) through diverse administration ways. However, the homing, survival, and differentiation potential of these differently administered BMSCs are poorly defined, and the best route of administration is not well-defined. Herein, we aim to compare the engraftment, retaining time, and therapeutic efficiency of differently administered BMSCs. To achieve this, GFP/Luc-labeled BMSCs administered in two modes were assessed in a thin endometrium rat model: either into the damaged horns directly or through the ipsilateral iliac artery. The retaining time and hemi-quantitative distribution were evaluated by in vivo bioluminescence imaging and immunohistological analysis. Locally administered BMSCs were strongly detected in the abdomen at the first 4 days post treatment but underwent a rapid decrease in luminescent signal afterward and were rarely found 28 days after treatment. In contrast, the retaining time of BMSCs injected through the iliac artery was longer, reflected by more GFP-positive cells detected in the uterine section 28 days post treatment. Differentiation toward endometrial stromal cells was observed. Both routes of administration contributed to the restoration of the damaged endometrium, showing a comparable increase in the endometrial thickness and a decrease in fibrosis. However, more importantly, higher expression of LIF and VEGF, better recruitment, and longer retainment were found in the intra-arterial administration, contributing to the establishment of the optimal administration mode in clinical practice.

Comparative Analysis of Topical Versus Intravenous Administration of Epsilon-Aminocaproic Acid on Blood Management in Total Knee Arthroplasty.

IntroductionAlthough the use of antifibrinolytics to reduce perioperative blood loss during total knee arthroplasty (TKA) has shown unequivocal benefit in regard to blood conservation, the best route of administration remains in question. This study tested the hypothesis that topical delivery of epsilon-aminocaproic acid (EACA) was superior to intravenous (IV) administration in the setting of primary TKA.MethodsThis cross-sectional study included a six-year retrospective chart review of TKA patients done by a single surgeon. Post-operative hemoglobin levels and the incidence of blood transfusions were compared among three patient subgroups: no EACA, topical EACA, or IV EACA. Key outcome measures included post-operative hemoglobin, need for post-operative transfusion, and length of hospital stay.ResultsOf the 668 patients included in this study, 351 (52.5%) received IV EACA, 298 (44.6%) received topical EACA, and 19 (2.8%) received no EACA. For the three-way comparisons, significant differences were observed for post-operative mean hemoglobin on day one (p < 0.001), day two (p < 0.001), and day three (p = 0.004), with consistently higher means for participants in the topical group. Eight patients required transfusions in the IV EACA group, but none were needed in the topical EACA group (p = 0.027). Length of stay was shortest for patients in the topical group, with 66% hospitalized for two days, while 84% of the IV group remained hospitalized for three days (p < 0.001).ConclusionsThe topical delivery of EACA is superior to IV administration with respect to blood conservation for patients undergoing primary TKA.

Transurethral Intraprostatic Botulinum Toxin-a Injection in Patients with Benign Prostatic Hyperplasia: A Case Series and Literature Review

Background: We aimed to assess the efficacy of Intraprostatic Onabotulinumtoxin-A (BTA) on the International Prostate Symptom Score (IPSS) and other objective measures of patients with Benign Prostatic Hyperplasia (BPH). Methods: Fifteen patients were included in this study. The drug (BTA; 150 IU) was reconstituted in 20 mL of 0.9% saline before administration to the patients. After providing urethral anesthesia, 20 intraurethral injections were made to lateral lobes of the prostate, 10 injections in each lobe. Follow-up visits were planned 3 and 12 months after the intervention. Pre- and post-interventional IPSS, Prostate-Specific Antigen (PSA), Prostate Volume (PV), Post-Void Residue (PVR), and maximum urinary flow rate (Qmax) compared via paired t-test. Finally, we reviewed the Pubmed database to provide a more precise conclusion. Results: The Mean±SD age of patients was 69±8.24 years, and the mean IPSS score decreased significantly from 24.3±3.3 to 14.6±3.7 (p&lt;0.001) and 16.86±3.06 (p&lt;0.009) on the 3rd and 12th months, respectively. The Mean±SD PSA, PVR, Qmax, and PV were 3.26±1.38, 82.33±35.55, 8.56±1.76, and 47.86±8.93, respectively at baseline. These factors significantly improved to 2.72±1.33 (P&lt;0.000), 71.33±30.55 (p&lt;0.000), 9.5±1.33 (p&lt;0.011), and 42.86± 6.04 (p&lt;0.000), respectively, on the 12th month follow-up. Conclusion: Although the overall results support the efficacy of BTA for BPH, the best route of administration, the most effective dose, the optimal number, and the volume of injections need further investigations. The probable placebo effect and underlying medical conditions (e.g., insulin resistance) should be considered as the confounding factors.

The role of Chito-oligosaccharide in regulating ovarian germ stem cells function and restoring ovarian function in chemotherapy mice

In recent years, the discovery of ovarian germ stem cells (OGSCs) has provided a new research direction for the treatment of female infertility. The ovarian microenvironment affects the proliferation and differentiation of OGSCs, and immune cells and related cytokines are important components of the microenvironment. However, whether improving the ovarian microenvironment can regulate the proliferation of OGSCs and remodel ovarian function has not been reported. In this study, we chelated chito-oligosaccharide (COS) with fluorescein isothiocyanate (FITC) to track the distribution of COS in the body. COS was given to mice through the best route of administration, and the changes in ovarian and immune function were detected using assays of organ index, follicle counting, serum estrogen (E2) and anti-Mullerian hormone (AMH) levels, and the expression of IL-2 and TNF-α in the ovaries. We found that COS significantly increased the organ index of the ovary and immune organs, reduced the rate of follicular atresia, increased the levels of E2 and AMH hormones, and increased the protein expression of IL-2 and TNF-α in the ovary. Then, COS and OGSCs were co-cultured to observe the combination of COS and OGSCs, and measure the survival rate of OGSCs. With increasing time, the fluorescence intensity of cells gradually increased, and the cytokines IL-2 and TNF-α significantly promoted the proliferation of OGSCs. In conclusion, COS could significantly improve the ovarian and immune function of chemotherapy model mice, and improve the survival rate of OGSCs, which provided a preliminary blueprint for further exploring the mechanism of COS in protecting ovarian function.

Lymphoscintigraphic Mapping in Melanoma and Breast Cancer.

In determining the best options for lymphoscintigraphy, investigators have tried many different radiopharmaceuticals and protocols. There are varying opinions on the best route of administration, timing for delayed images, and radiopharmaceutical. Debate around which radiopharmaceutical is best arises from the requirement that it clear from healthy lymph channels quickly enough to reveal the SLN. This paper reviews and compares 9 recognized publications on lymphoscintigraphy, illustrates the different preferences regarding the procedure, and describes the generally accepted protocols for the best way to locate the sentinel lymph node. Detailed explanations are given for the variable involvement of the sentinel lymph node and the variations in disease stage seen with different protocols. All discrepancies between protocols are supported with evidence such as positive results or false-positive results. On reading this paper, you will be able to form an opinion on the best protocols and radiopharmaceuticals and learn why lymphoscintigraphy is a crucial tool in improving a patient's prognosis.

Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell-derived tumor growth in vitro and in vivo.

Cancer stem cells (CSCs) are considered as responsible for initiation, maintenance and recurrence of solid tumors, thus representing the key for tumor eradication. The antitumor activity of extracellular vesicles (EVs) derived from different stem cell sources has been investigated with conflicting results. In our study, we evaluated, both in vitro and in vivo, the effect of EVs derived from human bone marrow mesenchymal stromal cells (MSCs) and from a population of human liver stem cells (HLSCs) of mesenchymal origin on renal CSCs. In vitro, both EV sources displayed pro‐apoptotic, anti‐proliferative and anti‐invasive effects on renal CSCs, but not on differentiated tumor cells. Pre‐treatment of renal CSCs with EVs, before subcutaneous injection in SCID mice, delayed tumor onset. We subsequently investigated the in vivo effect of MSC‐ and HLSC‐EVs systemic administration on progression of CSC‐generated renal tumors. Tumor bio‐distribution analysis identified intravenous treatment as best route of administration. HLSC‐EVs, but not MSC‐EVs, significantly impaired subcutaneous tumor growth by reducing tumor vascularization and inducing tumor cell apoptosis. Moreover, intravenous treatment with HLSC‐EVs improved metastasis‐free survival. In EV treated tumor explants, we observed both the transfer and the induction of miR‐145 and of miR‐200 family members. In transfected CSCs, the same miRNAs affected cell growth, invasion and survival. In conclusion, our results showed a specific antitumor effect of HLSC‐EVs on CSC‐derived renal tumors in vivo, possibly ascribed to the transfer and induction of specific antitumor miRNAs. Our study provides further evidence for a possible clinical application of stem cell‐EVs in tumor treatment.

Fate of systemically and locally administered adipose-derived mesenchymal stromal cells and their effect on wound healing.

There is increasing interest in the use of adipose‐derived mesenchymal stromal cells (ASCs) for wound repair. As the fate of administered cells is still poorly defined, we aimed to establish the location, survival, and effect of ASCs when administered either systemically or locally during wound repair under physiological conditions. To determine the behavior of ASCs, a rat model with wounds on the dorsal aspect of the hind paws was used and two treatment modes were assessed: ASCs administered systemically into the tail vein or locally around the wound. ASCs were transduced to express both firefly luciferase (Fluc) and green fluorescent protein to enable tracking by bioluminescence imaging and immunohistological analysis. Systemically administered ASCs were detected in the lungs 3 hours after injection with a decrease in luminescent signal at 48 hours and signal disappearance from 72 hours. No ASCs were detected in the wound. Locally administered ASCs remained strongly detectable for 7 days at the injection site and became distributed within the wound bed as early as 24 hours post injection with a significant increase observed at 72 hours. Systemically administered ASCs were filtered out in the lungs, whereas ASCs administered locally remained and survived not only at the injection site but were also detected within the wound bed. Both treatments led to enhanced wound closure. It appears that systemically administered ASCs have the potential to enhance wound repair distally from their site of entrapment in the lungs whereas locally administered ASCs enhanced wound repair as they became redistributed within the wound bed.

Neuroimaging and clinical trials with stem cells in amyotrophic lateral sclerosis: Present and future perspectives

Amyotrophic lateral sclerosis is a rare neurodegenerative disease with a rapid fatal course. The absence of effective treatments has led to new lines of research, some of which are based on stem cells. Surgical injection into the spinal cord, the most common route of administration of stem cells, has proven safe in trials to test the safety of the procedure. Nevertheless, challenges remain, such as determining the best route of administration or the way of checking the survival of the cells and their interaction with the therapeutic target. To date, the mission of neuroimaging techniques has been to detect lesions and complications in the spine and spinal cord, but neuroimaging also has the potential to supplant histologic study in analyzing the relations between the implanted cells and the therapeutic target, and as biomarkers of the disease, by measuring morphological and functional changes after treatment. These developments would increase the role of radiologists in the clinical management of patients with amyotrophic lateral sclerosis.

Neuroimagen y ensayos clínicos con células madre en la esclerosis lateral amiotrófica: perspectivas de presente y futuro

Amyotrophic lateral sclerosis is a rare neurodegenerative disease with a rapid fatal course. The absence of effective treatments has led to new lines of research, some of which are based on stem cells. Surgical injection into the spinal cord, the most common route of administration of stem cells, has proven safe in trials to test the safety of the procedure. Nevertheless, challenges remain, such as determining the best route of administration or the way of checking the survival of the cells and their interaction with the therapeutic target. To date, the mission of neuroimaging techniques has been to detect lesions and complications in the spine and spinal cord, but neuroimaging also has the potential to supplant histologic study in analyzing the relations between the implanted cells and the therapeutic target, and as biomarkers of the disease, by measuring morphological and functional changes after treatment. These developments would increase the role of radiologists in the clinical management of patients with amyotrophic lateral sclerosis.

Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials.

Faecal microbiota transplantation (FMT) has emerged as a useful approach for treating Clostridium difficile-associated diarrhoea (CDAD). Randomised controlled trials (RCTs) have recently evaluated its effectiveness, but systematic reviews have focused on evidence from case series. We therefore conducted a systematic review and meta-analysis of RCTs evaluating the effectiveness of FMT for treating CDAD. We included RCTs that primarily recruited adults with CDAD and compared the effectiveness of FMT with that of placebo, antibiotic therapy, or autologous stool transplantation, or compared different preparations or modes of delivery of FMT. Dichotomous symptom data were pooled to calculate a relative risk (RR) of CDAD persisting after therapy, and the number needed to treat (NNT). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched to 6 February 2017. We identified ten RCTs that evaluated the treatment of a total of 657 patients with CDAD. Five RCTs compared FMT with placebo (including autologous FMT) or vancomycin treatment (total of 284 patients); FMT was statistically significantly more effective (RR, 0.41; 95% CI, 0.22-0.74; NNT, 3; 95% CI, 2-7). Heterogeneity across studies was significant (I2 = 61%); this heterogeneity was attributable to the mode of delivery of FMT, and to the therapy being more successful in European than in North American trials. The other five RCTs evaluated different approaches to FMT therapy. Frozen FMT preparations were as efficacious as fresh material in one RCT, but the numbers of patients in the remaining RCTs were too small to allow definitive conclusions. Moderate quality evidence from RCT trials indicates that FMT is more effective in patients with CDAD than vancomycin or placebo. Further investigations are needed to determine the best route of administration and FMT preparation.