Single-incision robotic colorectal surgery with the da Vinci SP® surgical system: initial results of 50 cases.

PURPOSE: The da Vinci SP® (dVSP) surgical system (Intuitive Surgical, Sunnyvale, CA, USA), a robotic platform designed for single-incision surgery, overcame the need for multiple ports in traditional robotic surgery and issues including triangulation and retraction in single-incision laparoscopic surgery. However, previous studies only included case reports or series with small sample sizes. The aim of this study was to assess the safety and performance of the dVSP surgical system and its instruments and accessories for colorectal procedures. METHODS: The medical records of patients who had surgery with the dVSP from March 2019 to September 2021 at Ewha Womans University Seoul Hospital were investigated. The pathologic and follow-up data of patients who had malignant tumors were analyzed separately to evaluate oncological safety. RESULTS: Fifty patients (26 male and 24 female) with a median age of 59 years (interquartile range 52.5-63.0 years) were enrolled. The procedures included low anterior resection with total mesorectal excision (n = 16), sigmoid colectomy with complete mesocolic excision and central vessel ligation (CME + CVL) (n = 14), right colectomy with CME + CVL (n = 9), left colectomy with CME + CVL (n = 4), right colectomy (n = 6), and sigmoid colectomy (n = 1). Operative time significantly decreased after 25 cases (early phase vs. late phase; operative time 295.0 min vs. 250.0 min, p = 0.015; docking time 16.0 min vs. 12.0 min, p = 0.001; console time 212.0 min vs. 190.0 min, p = 0.019). Planned procedures were successfully completed in all patients. Postoperative outcomes were acceptable with only six cases of mild adverse events through a 3-month follow-up. No local recurrence and only one case of systemic recurrence occurred within 1 year postoperatively. CONCLUSIONS: This study demonstrated the surgical and oncological safety and feasibility of dVSP, which may be a novel surgical platform for colorectal surgery.

Augmented decision-making for acral lentiginous melanoma detection using deep convolutional neural networks.

BACKGROUND: Several studies have achieved high-level performance of melanoma detection using convolutional neural networks (CNNs). However, few have described the extent to which the implementation of CNNs improves the diagnostic performance of the physicians. OBJECTIVE: This study is aimed at developing a CNN for detecting acral lentiginous melanoma (ALM) and investigating whether its implementation can improve the initial decision for ALM detection made by the physicians. METHODS: A CNN was trained using 1072 dermoscopic images of acral benign nevi, ALM and intermediate tumours. To investigate whether the implementation of CNN can improve the initial decision for ALM detection, 60 physicians completed a three-stage survey. In Stage I, they were asked for their decisions solely on the basis of dermoscopic images provided to them. In Stage II, they were also provided with clinical information. In Stage III, they were provided with the additional diagnosis and probability predicted by the CNN. RESULTS: The accuracy of ALM detection in the participants was 74.7% (95% confidence interval [CI], 72.6-76.8%) in Stage I and 79.0% (95% CI, 76.7-81.2%) in Stage II. In Stage III, it was 86.9% (95% CI, 85.3-88.4%), which exceeds the accuracy delivered in Stage I by 12.2%p (95% CI, 10.1-14.3%p) and Stage II by 7.9%p (95% CI, 6.0-9.9%p). Moreover, the concordance between the participants considerably increased (Fleiss-κ of 0.436 [95% CI, 0.437-0.573] in Stage I, 0.506 [95% CI, 0.621-0.749] in Stage II and 0.684 [95% CI, 0.621-0.749] in Stage III). CONCLUSIONS: Augmented decision-making improved the performance of and concordance between the clinical decisions of a diverse group of experts. This study demonstrates the potential use of CNNs as an adjoining, decision-supporting system for physicians' decisions.

Mohs micrographic surgery for dermatofibrosarcoma protuberans: comparison of frozen and paraffin techniques.

BACKGROUND: Due to the propensity for local recurrence, Mohs micrographic surgery (MMS) has been suggested for the treatment of dermatofibrosarcoma protuberans (DFSP) and it has shown improved clinical outcomes. Recently, some authors suggested that MMS using paraffin-embedded sections (paraffin MMS) is superior in DFSP treatment compared with the conventional frozen MMS method. However, there have been no studies comparing frozen and paraffin MMS for the treatment of DFSP. OBJECTIVES: To compare the outcomes between DFSP patients who underwent frozen MMS and paraffin MMS. METHODS: Seventy-one DFSP patients treated with frozen MMS (n = 30) or paraffin MMS (n = 41) from 2003 to 2017 at a single institution were retrospectively reviewed. Recurrence rate and recurrence-free survival between frozen and paraffin MMS were assessed. RESULTS: During the mean follow-up duration of 25.4 months, four patients (frozen MMS, n = 1; and paraffin MMS, n = 3) showed recurrence after MMS. Although the local recurrence rate of the frozen MMS group (3.3%) was lower than that of the paraffin MMS group (7.3%), the difference was not statistically significant. In addition, recurrence-free survival was not significantly different between the two groups (P = 0.168). CONCLUSIONS: Frozen MMS, which has the advantages of shorter surgery time and immediate closure, is as effective as paraffin MMS in the treatment of DFSP.

Anakinra Protects Against Serum Deprivation-Induced Inflammation and Functional Derangement in Islets Isolated From Nonhuman Primates.

We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)-1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum-deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum-deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin-induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/- ) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation-induced impairment of in vitro viability and glucose-stimulated insulin secretion and attenuated serum deprivation-induced caspase-1 activation, transcription, and secretion of IL-1ß, IL-6, and tumor necrosis factor-α in hIAPP+/- mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets.

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic disorders.

Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain.

Survival and proliferation of cancer cells are often associated with hyperactivity of the serine/threonine kinase, Akt. Herein, we show that prosurvival activity of Akt can be converted into prodeath activity by embedding an Akt recognition sequence in the apoptogenic BH3 domain of human BIM. The recognition sequence was created by introducing two mutations, I155R and E158S, into the core region of the BIM BH3 domain. Although a 21-mer BIM BH3 peptide containing these two mutations bound weakly to BCL-XL and BCL-2, this peptide with phosphorylation of Ser158 bound to these proteins with a dissociation constant of <10 nM. The crystal structure of the phosphorylated peptide bound to BCL-XL revealed that the phospho-Ser158 makes favorable interactions with two BCL-XL residues, which cannot be formed with unphosphorylated Ser158. Remarkably, the designed peptide showed a cytotoxic effect on PTEN-null PC3 tumor cells whose Akt activity is aberrantly high. The cell-killing activity disappeared when the cellular Akt activity was lowered by ectopic PTEN expression. Thus, these results lay a foundation for developing a peptide or protein agent that is dormant in normal cells but is transformed into a potent apoptogenic molecule upon phosphorylation by hyperactivity of Akt in cancer cells.

Improved revascularization of islet grafts using an angiogenic monocyte subpopulation derived from spheroid culture of bone marrow mononuclear cells.

The spheroid culture method is an effective strategy for ex vivo expansion of an autologous therapeutic cell population. We investigated if cotransplantation of bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived mononuclear cells (BM-MNCs) could improve the posttransplant outcome of islet grafts using a mouse syngeneic marginal mass renal subcapsular islet transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice, the role of the BM-spheroids and the contribution of vessels derived from donors and recipients in grafted areas were assessed by immunohistochemistry. Compared to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM-spheroids, mainly composed of CXCR4(+) CD14(+) myeloid cells, showed higher angiogenic capacity, such as in vitro self-formed vessel structures; increased expression of angiogenic and chemoattractive factors; and incorporation into new vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation with islets improved the posttransplant outcomes in terms of glucose tolerance, serum insulin level, and diabetes reversal rate when compared with cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that cotransplantation of the BM-spheroids increased vessel density, area of grafted endocrine and non-endocrine tissue, and ß cell proliferation. In conclusion, cotransplantation of islets and BM-spheroids improved islet function through facilitation of revascularization and an increase in cell proliferation and islet cell mass.

Acupuncture for treatment of arthralgia secondary to aromatase inhibitor therapy in women with early breast cancer: pilot study.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer. A substantial proportion of women taking AIs experience joint pain and stiffness. Studies have suggested that acupuncture may be effective in treating joint pain. OBJECTIVE: A pilot study was conducted to evaluate the feasibility, safety and efficacy of using acupuncture to treat AI-induced arthralgia. METHODS: A total of 32 patients were randomised to receive either sham or real electroacupuncture (EA) twice weekly for 6 weeks. Outcomes of joint pain, stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), overall pain severity and interference with the BPI-SF and quality of life (QOL) with the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Hand strength was assessed by a grip test, and a serum marker of inflammation (C reactive protein (CRP)) was also measured. All assessments were performed at baseline, 6 weeks and 12 weeks, except for blood samples at baseline and 6 weeks only. RESULTS: No serious adverse events were reported during or after acupuncture treatments. There were no significant differences in outcome measures. However, positive trends were observed in stiffness and physical function at week 12 in favour of real EA. CONCLUSIONS: Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI. A larger study with adequately powered to confirm these results and detect clinically relevant effects is needed.

Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts.

Bone marrow-derived early endothelial progenitor cells (BM-EPCs) are a clinical tool for enhancing revascularization. However, the therapeutic efficacy of co-transplantation of BM-EPC with islets has not been investigated. In this study, marginal mass islets were co-transplanted with or without BM-EPCs under the kidney capsules of syngeneic streptozotocin-induced diabetic mice. Using green fluorescent protein transgenic (GFP-Tg) mice as BM-EPC and islet donors or recipients, the role of EPCs in revascularization was assessed for graft morphology, vascular density and fate of EPCs by immunohistochemistry. Islet-EPC co-transplantation improved the outcome of islet transplantation as measured by glucose tolerance, serum insulin level and diabetes reversal rate, compared with transplantation of islets alone. Between groups, the morphology of islet grafts showed significant differences in size and composition of grafted endocrine tissues. Significantly more vessel density derived from donors and recipients was detected with islet-EPC co-transplantation. Abundant GFP-Tg mice-derived BM-EPCs (GFP-EPCs) were observed in or around islet grafts and incorporated into CD31-positive capillaries. Remaining GFP-EPCs expressed VEGF. In conclusion, co-transplantation of islets with BM-EPCs could improve the outcome of marginal mass islet transplantation by promoting revascularization and preserving islet morphology.

Comparison of negative pressure wound therapy and secondary intention healing after excision of acral lentiginous melanoma on the foot.

BACKGROUND: Melanoma in dark-skinned individuals often develops in an acral lentiginous fashion on the foot and wide excision usually results in a substantial defect. Various repair methods, including free flap, full-thickness skin graft and secondary intention healing (SIH), are used to repair these defects. Recently, use of negative pressure wound treatment (NPWT) has been shown to accelerate wound healing in different types of wound. OBJECTIVES: To compare the functional and cosmetic results of NPWT and SIH in patients who underwent wide excision of melanomas on the foot. METHODS: The wound defects of 22 patients after wide excision of melanoma on the foot were treated using SIH (n = 13) or NPWT (n = 9). RESULTS: There was no significant difference in time to complete wound healing between the two groups. However, evaluation using the Vancouver Burn Scar Assessment Scale at the time of complete healing showed that the mean score of the NPWT group was significantly lower than that of the SIH group. The NPWT group also had significantly better results than the SIH group in terms of total score, vascularity and height of the scars. As for complications, no wound infection was encountered in the NPWT group, whereas eight of the 13 patients in SIH group had wound infections during the course of treatment despite frequent and meticulous aseptic dressing changes. CONCLUSIONS: These results show that, despite the drawback of rather prolonged healing time, NPWT is an excellent therapeutic option for wounds after wide excision of melanoma on the foot, with acceptable functional and cosmetic outcomes.

Acute necrotic stomatitis (noma) associated with methicillin-resistant Staphylococcus aureus infection in a newly acquired rhesus macaque (Macaca mulatta).

BACKGROUND: A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. METHODS: To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. RESULTS: Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin-resistant Staphylococcus aureus infection. Vancomycin and ampicillin-sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. CONCLUSIONS: Simian noma associated with methicillin-resistant Staphylococcus aureus (MRSA) had not previously been reported in non-human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.

Downregulation of autophagy by Bcl-2 promotes MCF7 breast cancer cell growth independent of its inhibition of apoptosis.

The anti-apoptotic Bcl-2 protein, which confers oncogenic transformation and drug resistance in most human cancers, including breast cancer, has recently been shown to effectively counteract autophagy by directly targeting Beclin1, an essential autophagy mediator and tumor suppressor. However, it remains unknown whether autophagy inhibition contributes to Bcl-2-mediated oncogenesis. Here, by using a loss-of-function mutagenesis study, we show that Bcl-2-mediated antagonism of autophagy has a critical role in enhancing the tumorigenic properties of MCF7 breast cancer cells independent of its anti-apoptosis activity. A Bcl-2 mutant defective in apoptosis inhibition but competent for autophagy suppression promotes MCF7 breast cancer cell growth in vitro and in vivo as efficiently as wild-type Bcl-2. The growth-promoting activity of this Bcl-2 mutant is strongly correlated with its suppression of Beclin1-dependent autophagy, leading to sustained p62 expression and increased DNA damage in xenograft tumors, which may directly contribute to tumorigenesis. Thus, the anti-autophagic property of Bcl-2 is a key feature of Bcl-2-mediated oncogenesis and may in some contexts, serve as an attractive target for breast and other cancer therapies.

Non-synonymous single-nucleotide polymorphisms associated with blood pressure and hypertension.

In this study, we determined the association of 1180 non-synonymous single-nucleotide polymorphisms (SNPs) with systolic blood pressure (SBP) and hypertensive status. A total of 8842 subjects were taken from two community-based cohorts--Ansung (n=4183) and Ansan (n=4659), South Korea--which had been established for genome-wide association studies (GWAS). Five SNPs (rs16835244, rs2286672, rs6265, rs17237198 and rs7312017) were significantly associated (P-values: 0.003-0.0001, not corrected for genome-wide significance) with SBP in both cohorts. Of these SNPs, rs16835244 and rs2286672 correlated with risk for hypertension. The rs16835244 SNP replaces Ala288 in arginine decarboxylase (ADC) with serine, and rs2286672 replaces Arg172 in phospholipase D2 (PLD2) with cysteine. A comparison of peptide sequences between vertebrate homologues revealed that the SNPs identified occur at conserved amino-acid residues. In silico analysis of the protein structure showed that the substitution of a polar residue, serine, for a non-polar alanine at amino-acid residue 288 affects a conformational change in ADC, and that Arg172 in PLD2 resides in the PX domain, which is important for membrane trafficking. These results provide insights into the function of these non-synonymous SNPs in the development of hypertension. The study investigating non-synonymous SNPs from GWAS not only by statistical association analysis but also by biological relevance through the protein structure might be a good approach for identifying genetic risk factors for hypertension, in addition to discovering causative variations.

Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial.

BACKGROUND: Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients. PATIENTS AND METHODS: One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially. RESULTS: Regression analysis indicated that the MQ group significantly improved overall QOL (t(144) = -5.761, P < 0.001), fatigue (t(153) = -5.621, P < 0.001), mood disturbance (t(122) =2.346, P = 0.021) and inflammation (CRP) (t(99) = 2.042, P < 0.044) compared with usual care after controlling for baseline variables. CONCLUSIONS: This study indicates that MQ can improve cancer patients' overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation.

Genetic variations in ATP2B1, CSK, ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohorts.

Blood pressure, one of the important vital signs, is affected by multiple genetic and environmental factors. Recently, several genome-wide association (GWA) studies have successfully identified genetic factors that influence blood pressure and hypertension risk. In this study, we report results of the Korean Association REsource (KARE, 8842 subjects) GWA study on blood pressure and hypertension risk. In all, 10 single-nucleotide polymorphisms (SNPs) that showed significant association with hypertension were further analysed for replication associations in the Health2 project (7861 subjects). Among these 10 SNPs, 3 were replicated in the Health2 cohort for an association with systolic or diastolic blood pressure. The most significant SNP (rs17249754 located in ATPase, Ca(++) transporting, plasma membrane 1 (ATP2B1)) has been previously reported, and the other two SNPs are rs1378942 in the c-src tyrosine kinase (CSK) gene and rs12945290 in the arylsulphatase G (ARSG) gene. An additional hypertension case-control study confirmed that rs17249754 (in ATP2B1) increases hypertension risk in both the KARE and Health2 (meta-analysis, P-value=4.25 x 10(-9)) cohorts. One more SNP, rs995322, located in the CUB and Sushi multiple domains 1 (CSMD1), is also associated with increased risk of hypertension (meta-analysis, P-value=1.00 x 10(-4)). Despite the difficulty of obtaining replication results for a complex trait genetic association between blood pressure and hypertension, we were able to identify consistent genetic factors in both the Korean cohorts in ATP2B1, CSK, ARSG and CSMD1 genes.

Ribosomal protein S6 is a selective mediator of TRAIL-apoptotic signaling.

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis in tumor cells and holds a promise as a therapeutic agent against cancer. To elucidate the death signaling evoked by TRAIL, we performed a functional genetic screening and rescued TRAIL-resistant Jurkat clones harboring ribosomal protein S6 (rpS6) cDNA in anti-sense frame. Reduction of rpS6 expression in Jurkat and HeLa cells attenuated apoptosis induced by TRAIL, but not those by other cell death signals, including tumor necrosis factor-alpha and cycloheximide, etoposide, doxorubicin, tunicamycin and staurosporine. Death receptor (DR) 4, but not DR5, was downregulated in rpS6 knockdown cells. Conversely, the sensitivity to TRAIL was increased by the ectopic expression of wild-type rpS6 and further by phospho-defective rpS6 mutant (S6-SS235,6AA), but not by phospho-mimic rpS6 mutant (S6-SS235,6DD). Also, unphosphorylatable rpS6 knock-in mouse embryo fibroblasts (rpS6(P-/-) MEFs) were more sensitive to TRAIL than control MEFs. In addition, SKHep-1 tumor cells, which express less phospho-rpS6 and are more sensitive to TRAIL than other tumor cells, became effectively desensitized to TRAIL after rpS6 knockdown. These results suggest that rpS6, especially in its unphosphorylated form, is a selective mediator of TRAIL-induced apoptosis.

Restoration of left ventricular synchronous contraction after acute myocardial infarction by stem cell therapy: new insights into the therapeutic implication of stem cell therapy for acute myocardial infarction.

OBJECTIVE: To evaluate the effects of stem cell therapy on restoration of the left ventricular (LV) synchronous contraction in patients with acute myocardial infarction (AMI). METHODS: 40 patients with AMI who underwent successful coronary revascularisation were randomly allocated to the cell infusion or the control group. Evaluations were performed with echocardiographic tissue synchronisation imaging to determine LV dyssynchrony and with cardiac magnetic resonance imaging to estimate LV ejection fraction (LVEF) at baseline and at 6 months. To quantify the severity of systolic LV dyssynchrony, the standard deviations of time to peak systolic velocity of the 12 LV segments (Ts-SD) were calculated. RESULTS: At 6 months, greater improvements of Ts-SD (DeltaTs-SD: -45.0 (40.2) vs 5.0 (39.9) ms, p<0.001) and LVEF (DeltaLVEF: 6.8% (9.1%) vs -0.2% (6.9%), p = 0.015) relative to the corresponding baseline values were observed in the cell infusion group than in the control group. By multivariate analysis, DeltaTs-SD and baseline LVEF emerged as the independent determinants of LVEF improvement and cell infusion, and baseline Ts-SD as the determinant of DeltaTs-SD improvement. Maximal exercise capacity measured by symptom-limited treadmill testing correlated well with Ts-SD but not with LVEF at 6 months of follow-up. CONCLUSION: Stem cell therapy had a favourable effect on the restoration of LV synchronous contraction in patients with AMI.

Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population.

OBJECTIVE: Disruption of the vascular supply to the bone and subsequent hypoxia has been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Vascular endothelial growth factor (VEGF), a major inducer of angiogenesis, has been correlated with several pathological conditions, from inflammation to ischemic processes. A number of polymorphisms in the VEGF gene have been described as being associated with several diseases, such as diabetic retinopathy, prostate cancer and breast cancer. The aim of this study was to evaluate the association of VEGF gene polymorphisms with ONFH in a case--control study. METHODS: Three polymorphisms (-2578C>A, -634G>C and +936C>T) in VEGF were genotyped in 317 ONFH patients and 497 control subjects, using the TaqMan 5' allelic discrimination assay. We performed the association analysis of genotyped single nucleotide polymorphisms (SNPs) and haplotypes with ONFH. RESULTS: The -634G>C genotype was significantly associated with an increased risk for ONFH in dominant model with odds ratio (OR) of 1.47, 95% confidence intervals (CIs) 1.08-2.01 with P value 0.015. Further analysis stratified by sex showed that the -634G>C genotype was also significantly associated with a high risk for male patients considering the dominant model with OR of 1.60, 95% CI 1.13-2.26 with P value 0.008. Haplotype association analysis did not provide a further delineation of the risk allele. CONCLUSION: Our study is, to our knowledge, the first report that shows the -634G>C polymorphism in the VEGF promoter was associated with an increased susceptibility of ONFH in the Korean population.