Document Type : Review


Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.


There is a substantial amount of data provided in preclinical research and recently made early clinical efforts to evaluate the positive MSC therapy in Limb ischemia disease impacts. The present review is primarily focused on assessing various limb ischemia-related human MSC clinical trials to select the best technique with the highest limb ischemia-related clinical trial MSC efficacy. Five studies met the criteria to be included in this review. MSCs originating from bone marrow Allogenic MSC, bone marrow autogenous MSCs, HUCB MSCs were administered. The injection was intramuscular, Intravenous, and intravenous. The mean follow-up time was between 6 to 60months after MSC therapy. All studies reported improvement from baseline in at least 1 clinical outcome measure, and no study reported major adverse events attributable to MSC therapy. In clinical assessments, the selection of the best method could improve treatment efficacy. Several factors may be involved in the MSC injection efficacy of limb ischemia patients. Both allogeneic and autologous exhibited positive results over placebo. However, it is should be mentioned that autologous MSC investigation has higher cost and toxicity. To reduce the toxicity of derived MSCs while injection, particularly in arterial and intravenous injection, different injection doses can be performed. MI injection at different doses is the best method for diminishing the side effects. To evaluate injection efficacy, different criteria can be adopted, including angiography, ABI index, ulcer healing and amputation, and pain-free walking distance follow-up for up to five years.


Despite the therapeutic novelty of MSC utilization for limb ischemia treatment, there is a substantial amount of data provided in preclinical research and recently-made early clinical efforts to evaluate the positive MSC therapy impacts. In this approach, the patient type is an essential factor1. In general, it is required to obtain consensus on various important aspects. Although peripheral vascular disease is most commonly caused by atherosclerosis, Buerger’s disease (which is also referred to as thromboangiitis obliterans) represents a less frequently-observed yet important cause (2). 

Buerger’s disease refers to an inflammatory disorder that distinctly differs from the vascular occlusive disease afflicting young smoker’s peripheral arteries (3). A characteristic of this disorder is an inexorable downhill course that occurs even among people that cease smoking after reaching s limb ischemia stage relating to gangrene or ulceration (4).
Cell dosing is also an essential factor (5). Efficacy was seemingly not impacted by the administration site and total cell count. Furthermore, the current regimes (6). It is important that associated clinical endpoints are incorporated into future clinical trials beyond the quality of life, walking time, and ankle-brachial index measurements (7). The Society for Vascular Surgery introduced particular objective performance goals (OPGs) for the purpose of defining therapeutic revascularization benchmarks concerning limb ischemia. Research has shown post-administration follow-up to last from three to twelve months (8). 
The Society for Vascular Surgery proposed thirty days of assessing safety endpoints, such as amputation, MLAE, and MACE as the standard time for post-procedural events and new devices (9). The present review is primarily focused on assessing various limb ischemia-related human MSC clinical trials to select the best technique with the highest limb ischemia-related clinical trial MSC efficacy.












































literature review 
 is a hospital based prospective study done in a tertiarycentre. Thirty patients with tibial plateau fractures who were operated with locking plates between 2015 and 2016 were followed for 18 months.Consent was taken from each patient before their participation in the study. 
After proper evaluation in the emergency department all patients underwent Xrays and CT scan for proper delineation of fracture site.Patients of either sex above 18 years with radiological evidence of tibial plateau fractures were considered for the study. Patients who had pre-existing arthritis of knee, congenital anomalies of knee, any previous surgery of the same knee, open trauma, those with compartment syndrome of the ipsilateral leg and polytrauma patients were not included in the study.
Patients who had pre-existing arthritis of knee, congenital anomalies of knee, any previous surgery of the same knee, open trauma, those with
compart ment syndrome of the ipsilateral leg and polytrauma patients were not included in the study.
Depending on the fracture type and site, two aplowing surgery, knee range of motions was started as soon as pain subsided usually after 2nd post op day.Postoperatively all patients were assessed after discharge at 2 weeks. Then four weekly till bony union occurred and after that three monthly till last follow up at 18 months.The functional outcome was evaluated using Rasmussen Functional Knee Score (Table 1) which was further graded according to score into Excellent, Good, Fair and Poor6.Post traumatic arthritic changes were graded according to Kellgren Lawrence grading. At 18 months all patients were checked clinically for limb malalignment.
Patients were also interviewed at 18 months regarding return to work. Sample size was 30. Chi square test and ANOVA test was used to calculate p-value depending on categorical and numerical data. Any p-value calculated < 0.05 was taken to be significant. Standard statistical analysis was done using SPSS version 18.

This prospective study was conducted at Central Institute of Orthopaedics, Safdarjung Hospital, New Delhi, India during the period of January 2015 to June 2017. Thirty patients withaverage age 42.4yearswith tibial plateau fractures were enrolled for the study which were fixed with open reduction and internal fixation with locking compression plates (Figure 1).



























The present study showed that the prevalence of febrile seizures was associated with gender, living place, temperature, family history of seizure, and the serum level of zinc. In this regard, the frequency of zinc deficiency was higher in patients with febrile seizures compared to febrile patients without seizure, before and after adjusting for gender. 
Zinc plays a vital role in the neuronal terminals of the hippocampus and amygdala by producing pyridoxal phosphate and affecting glutamatergic, gamma-aminobutyric acidergic (GABAergic), and glycinergic synapses (13).
Glutamic acid decarboxylase (GAD) acts as a major inhibitory neurotransmitter in the synthesis of gamma-aminobutyric acid (GABA) (14). A study by Ganesh R. and Janakiraman L. on 38 children with febrile convulsion and 38 children as a control group, aged between 3 months and 5 years, indicated that a serum zinc deficiency was significantly more prevalent in their case group than in the control group (15). Another study has reported that there is a correlation between disruption in Zn2+ homeostasis and fever seizure (16).
In studies by Papierkowski A., Mollah M.A., and Gündüz Z. et al., the mean serum zinc level in the febrile convulsion group was significantly lower than in the control group, which indicates the role of zinc in febrile seizure. Comparing the groups in terms of age and gender, no significant difference was found, similar to our study (17-19). Abdel Hameed Z.A. et al. (20), in a study on 100 infants in Egypt, observed that temperature had no significant difference between the case and control groups. But Berg A.T. (21), Ahmed B.W. (22), and our study showed the importance of temperature in febrile seizure. The geographic area can be the cause of this difference. Duangpetsang J. in a study from 2014 to 2017 reported that a high fever with electrolyte disturbance hyponatremia has an important role in FS (23). Sharifi R. et al., in a study in 2007-2014, showed the importance of family history in febrile seizure (24), which is similar to our results.

The findings of this study show that zinc deficiency is significantly associated with the occurrence of febrile seizures. Zinc supplementation in children can therefore be helpful for the prevention and treatment of FS.

Conflict of interest
The authors declare no conflicts of interest.


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