Stem Cell Treatment for Diabetic Foot Ulcers: A Meta-analysis of Randomized Clinical Trials.

GENERAL PURPOSE: To provide information on the efficacy of stem cells in the treatment of diabetic foot ulcers. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will: 1. Explain outcomes from the use of stem cell treatment for diabetic foot ulcers. 2. Identify features in the methodology of randomized controlled trials examining the efficacy of stem cells in the treatment of diabetic foot ulcers.

To assess the efficacy of stem cells in the treatment of diabetic foot ulcers. The authors searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases. The preliminary search identified 343 articles. After screening, 16 articles reporting 19 randomized controlled trials were included in the meta-analysis. The 16 articles included a total of 766 patients (400 in stem cell groups, 366 in control groups). Extracted data included: first author, publication date, patient characteristics, ulcer size, stem cell type and dose, follow-up time, evaluation index (eg, cure rate, amputation rate, pain-free walking distance), and adverse events. The stem cell group had a higher ulcer healing rate compared with the control group (odds ratio [OR], 5.16; 95% CI, 3.60­7.40; P < .00001); the mesenchymal stem cell and mononuclear cell groups had higher ulcer healing rates (OR, 3.98; 95% CI, 2.05­7.73; P < .0001; and OR, 12.85; 95% CI, 4.36­37.82; P < .0001, respectively). Seven articles reported amputation rates, which were lower in the treatment group than the control group (OR, 0.18; 95% CI, 0.08­0.41; P < .0001). Pain-free walking distance increased more after treatment in the stem cell group (standardized mean difference, 1.27; 95% CI, 0.89­1.65; P < .00001). Although 14 articles reported 92 adverse events, there was no association between stem cell infusion and adverse events. Stem cell therapy is an effective treatment strategy that can improve patient symptoms.

Outcomes of Anticoagulant Therapy with Low-Molecular-Weight Heparin (LMWH) and Warfarin for Thromboangiitis Obliterans (TAO).

BACKGROUND: Thromboangiitis obliterans (TAO) is a chronic, non-atherosclerotic, progressive inflammatory vascular disease affecting the small- and medium-size arteries and veins of the extremities. OBJECTIVE: To evaluate whether long-term anticoagulation with low-molecular-weight heparin (LMWH) and warfarin is beneficial for treating the inflammation and symptoms associated with TAO. METHODS: Patients with TAO who underwent anticoagulation as the mainstay of treatment were included in this prospective study. Rest pain relief and healing of trophic lesions (as the primary and secondary endpoint) were investigated at Day 14 and after 6 months of follow-up. High sensitivity C-reactive protein (hsCRP), monocyte count, and ankle-brachial index (ABI) were recorded, and the difference was compared before and after 2-week anticoagulation. The Chi-square test was used to compare the difference between anticoagulant and aspirin groups (based on the literature). RESULTS: From 2014 to 2019, 18 patients were included. Only 1 patient with wet gangrene received endo-therapy for a failing stent at the start of treatment. After ~14 days, 12 of 13 (92%) patients showed complete ulcer healing, and 17 of 18 (94%) patients showed complete relief from rest pain. Monocyte-counts and hsCRP levels decreased significantly (p<0.001) after a 2-week period of anticoagulation with LMWH. The mean follow-up was 2.6 years (range 0.5-5 years). At 6 months, all patients showed relief of rest pain and complete healing of trophic lesions. All endpoints were significantly improved compared with the aspirin group (p<0.01), and no rest pain or ulcer/gangrene recurred during follow-up. CONCLUSION: Anticoagulant therapy may alleviate the inflammation and symptoms of TAO.

Comparative proteome analysis of Helicobacter pylori clinical strains by two-dimensional gel electrophoresis.

OBJECTIVE: To investigate the pathogenic properties of Helicobacter pylori by comparing the proteome map of H. pylori clinical strains. METHODS: Two wild-type H. pylori strains, YN8 (isolated from biopsy tissue of a gastric cancer patient) and YN14 (isolated from biopsy tissue of a gastritis and duodenal ulcer patient), were used. Proteomic analysis, using a pH range of 3-10 and 5-8, was performed. The individual proteins were identified by quadrupole time-of-flight (Q-TOF) mass spectrometer and protein database search. RESULTS: Variation in spot patterns directed towards differential protein expression levels was observed between the strains. The gel revealed prominent proteins with several protein "families". The comparison of protein expressions of the two strains reveals a high variability. Differentially present or absent spots were observed. Nine differentially expressed protein spots identified by Q-TOF included adenosine triphosphate (ATP)-binding protein, disulfide oxidoreductase B (DsbB)-like protein, N utilization substance A (NusA), ATP-dependent protease binding subunit/heat shock protein, hydantoin utilization protein A, seryl-tRNA synthetase, molybdenum ABC transporter ModD, and hypothetical proteins. CONCLUSIONS: This study suggests that H. pylori strains express/repress protein variation, not only in terms of the virulence proteins, but also in terms of physiological proteins, when they infect a human host. The difference of protein expression levels between H. pylori strains isolated from gastric cancer and gastritis may be the initiator of inflammation, and result in the different clinical presentation. In this preliminary study, we report seven differential proteins between strains, with molecule weights from approximately 10 kDa to approximately 40 kDa. Further studies are needed to investigate those proteins and their function associated with H. pylori colonization and adaptation to host environment stress.