OBJECTIVES: To compare the efficacy and safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients.
SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and trials registries (16 May 2018). Review authors searched PubMed until February 2017.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving 'no-option' CLI patients comparing a particular source or regimen of autologous cell-based therapy against another source or regimen of autologous cell-based therapy.
DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility and methodological quality of the trials. We extracted outcome data from each trial and pooled them for meta-analysis. We calculated effect estimates using a risk ratio (RR) with 95% confidence interval (CI), or a mean difference (MD) with 95% CI.
MAIN RESULTS: We included seven RCTs with a total of 359 participants. These studies compared bone marrow-mononuclear cells (BM-MNCs) versus mobilised peripheral blood stem cells (mPBSCs), BM-MNCs versus bone marrow-mesenchymal stem cells (BM-MSCs), high cell dose versus low cell dose, and intramuscular (IM) versus intra-arterial (IA) routes of cell implantation. We identified no other comparisons in these studies. We considered most studies to be at low risk of bias in random sequence generation, incomplete outcome data, and selective outcome reporting; at high risk of bias in blinding of patients and personnel; and at unclear risk of bias in allocation concealment and blinding of outcome assessors. The quality of evidence was most often low to very low, with risk of bias, imprecision, and indirectness of outcomes the major downgrading factors.Three RCTs (100 participants) reported a total of nine deaths during the study follow-up period. These studies did not report deaths according to treatment group.Results show no clear difference in amputation rates between IM and IA routes (RR 0.80, 95% CI 0.54 to 1.18; three RCTs, 95 participants; low-quality evidence). Single-study data show no clear difference in amputation rates between BM-MNC- and mPBSC-treated groups (RR 1.54, 95% CI 0.45 to 5.24; 150 participants; low-quality evidence) and between high and low cell dose (RR 3.21, 95% CI 0.87 to 11.90; 16 participants; very low-quality evidence). The study comparing BM-MNCs versus BM-MSCs reported no amputations.Single-study data with low-quality evidence show similar numbers of participants with healing ulcers between BM-MNCs and mPBSCs (RR 0.89, 95% CI 0.44 to 1.83; 49 participants) and between IM and IA routes (RR 1.13, 95% CI 0.73 to 1.76; 41 participants). In contrast, more participants appeared to have healing ulcers in the BM-MSC group than in the BM-MNC group (RR 2.00, 95% CI 1.02 to 3.92; one RCT, 22 participants; moderate-quality evidence). Researchers comparing high versus low cell doses did not report ulcer healing.Single-study data show similar numbers of participants with reduction in rest pain between BM-MNCs and mPBSCs (RR 0.99, 95% CI 0.93 to 1.06; 104 participants; moderate-quality evidence) and between IM and IA routes (RR 1.22, 95% CI 0.91 to 1.64; 32 participants; low-quality evidence). One study reported no clear difference in rest pain scores between BM-MNC and BM-MSC (MD 0.00, 95% CI -0.61 to 0.61; 37 participants; moderate-quality evidence). Trials comparing high versus low cell doses did not report rest pain.Single-study data show no clear difference in the number of participants with increased ankle-brachial index (ABI; increase of > 0.1 from pretreatment), between BM-MNCs and mPBSCs (RR 1.00, 95% CI 0.71 to 1.40; 104 participants; moderate-quality evidence), and between IM and IA routes (RR 0.93, 95% CI 0.43 to 2.00; 35 participants; very low-quality evidence). In contrast, ABI scores appeared higher in BM-MSC versus BM-MNC groups (MD 0.05, 95% CI 0.01 to 0.09; one RCT, 37 participants; low-quality evidence). ABI was not reported in the high versus low cell dose comparison.Similar numbers of participants had improved transcutaneous oxygen tension (TcO₂) with IM versus IA routes (RR 1.22, 95% CI 0.86 to 1.72; two RCTs, 62 participants; very low-quality evidence). Single-study data with low-quality evidence show a higher TcO₂ reading in BM-MSC versus BM-MNC groups (MD 8.00, 95% CI 3.46 to 12.54; 37 participants) and in mPBSC- versus BM-MNC-treated groups (MD 1.70, 95% CI 0.41 to 2.99; 150 participants). TcO₂ was not reported in the high versus low cell dose comparison.Study authors reported no significant short-term adverse effects attributed to autologous cell implantation.
AUTHORS' CONCLUSIONS: Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.
METHODS: A literature search was performed on PUBMED, SCOPUS AND EMBASE. The following keywords were used: ethmoidal artery; anterior ethmoidal artery; anterior ethmoidal canal; ethmoid sinus; ethmoid roof; skull base. The search was conducted over a period of 6 months between October 2016 and April 2017.
RESULTS: 105 articles were retrieved. 76 articles which were either case reports or unrelated topics were excluded. Out of the 29 full text articles retrieved, 16 articles were selected; 3 were cadaveric dissection, 5 combined cadaveric dissection and computed tomography (CT) and the rest were of CT studies. All studies were of level III evidence and a total of 1985 arteries were studied. Its position at the skull base was influenced by the presence of supraorbital ethmoid cell (SOEC) and length of the lateral lamella of cribriform plate (LLCP). Inter population morphological variations contribute to the anatomical variations.
CONCLUSIONS: The average diameter of AEA was 0.80 mm and the intranasal length was 5.82 mm. 79.2% was found between the second and third lamellae, 12.0% in the third lamella, 6% posterior to third lamella and 1.2% in the second lamella. Extra precaution should be taken in the presence of a well-pneumatized SOEC and a long LLCP as AEA tends to run freely below skull base.
METHODS: A cross-sectional study of 252 AEA identified by computed tomography (CT) of the paranasal sinuses. The multiplanar CT images were acquired from SOMATOM® Definition AS+ and reconstructed to axial, coronal and sagittal view at 1 mm slice thickness.
RESULTS: 42.5% of AEA was within skull base (grade I), 20.2% at skull base (grade II) and 37.3% coursed freely below skull base (grade III). The prevalence of supraorbital ethmoid cell (SOEC) and suprabullar cell (SBC) was 29.8% and 48.0%. The position of AEA at skull base has significant association with SOEC (p
BACKGROUND: Channa striatus, also known as haruan, is a fresh water snakehead fish consumed in many parts of Southeast Asia. Channa striatus is also normally consumed by women postpartum to promote wound healing as well as to reduce post-operative pain.
METHODOLOGY: This study is a randomised, double blind, placebo-controlled study conducted in women after Lower Segment Caesarean Section (LSCS). Subjects were randomised to either a Channa striatus or a placebo group and were given a daily dosage of 500 mg of Channa striatus extract or 500 mg maltodextrin, respectively, for six weeks post LSCS. The anteroposterior measurements of the uterus in the longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine and superficial skin wound arteries were assessed using pelvic Gray-scale ultrasound and Doppler ultrasound at baseline (Day 3) and at two weeks, four weeks and six weeks post-operatively.
RESULTS: Sixty-six subjects were randomised into the study with 33 in the Channa striatus group and 33 in the placebo group. No significant differences were detected in terms of the pulsatility index (PI) and the resistive index (RI) of the uterine and superficial skin wound arteries between the Channa striatus and placebo groups. However, in the Channa striatus group, the AP measurements of the uterus on the longitudinal and oblique transverse planes were significantly lower compared to the placebo group (p<0.05 and p<0.001, respectively).
CONCLUSION: Daily intake of Channa striatus extract results in marked differences compared to placebo in terms of uterine involution and recovery in women post LSCS.
TRIAL REGISTRATION: www.isrctn.com 11960786.
METHODS: MCF-7 and MDA-MB231 cells were treated with several concentrations of FKA. The apoptotic analysis was done through the MTT assay, BrdU assay, Annexin V analysis, cell cycle analysis, JC-1 mitochondrial dye, AO/PI dual staining, caspase 8/9 fluorometric assay, quantitative real time PCR and western blot. For the metastatic assays, the in vitro scratch assay, trans-well migration/invasion assay, HUVEC tube formation assay, ex vivo rat aortic ring assay, quantitative real time PCR and western blot were employed.
RESULTS: We have investigated the effects of FKA on the apoptotic and metastatic process in two breast cancer cell lines. FKA induces apoptosis in both MCF-7 and MDA-MB231 in a dose dependent manner through the intrinsic mitochondrial pathway. Additionally, FKA selectively induces a G2/M arrest in the cell cycle machinery of MDA-MB231 and G1 arrest in MCF-7. This suggests that FKA's anti-cancer activity is dependent on the p53 status. Moreover, FKA also halted the migration and invasion process in MDA-MB231. The similar effects can be seen in the inhibition of the angiogenesis process as well.
CONCLUSIONS: FKA managed to induce apoptosis and inhibit the metastatic process in two breast cancer cell lines, in vitro. Overall, FKA may serve as a promising candidate in the search of a new anti-cancer drug especially in halting the metastatic process but further in vivo evidence is needed.