Isokinetic knee strength and proprioception before and after anterior cruciate ligament reconstruction: A comparison between home-based and supervised rehabilitation.

BACKGROUND: Rehabilitation after anterior cruciate ligament (ACL) reconstruction focuses on restoring knee deficiencies and function. However, the extent of the clinician's direct supervision that is required to recover knee function is unknown. OBJECTIVE: To investigate differences in isokinetic knee strength improvement, endurance, and proprioception between home-based (HBR) and supervised rehabilitation (SR). METHODS: Thirty participants were randomly allocated to each group after reconstruction. Isokinetic knee strength and proprioception were measured using the Biodex multi-joint and stability systems, respectively, before and after intervention. RESULTS: The SR group showed a significant improvement from baseline, but not the HBR group (SR group, from 1.94 ± 1.44 to 1.02 ± 0.92, p< 0.05; HBR group, from 1.69 ± 0.88 to 1.61 ± 0.90, p> 0.05). There was a significant effect of exercise type on proprioception scores after controlling for pretest values (p< 0.05). No significant difference in isokinetic knee strength was observed between the groups. CONCLUSIONS: HBR recovered knee strength as effectively as the SR, but SR was more effective than HBR for the recovery of proprioception and functional knee movement. This result indicates that guidance from health professionals play an important role in enhancing proprioception for patients following ACL reconstruction.

Nedd4 Deficiency in Vascular Smooth Muscle Promotes Vascular Calcification by Stabilizing pSmad1.

The nonosseous calcification process such as atherosclerosis is one of the major complications in several types of metabolic diseases. In a previous study, we uncovered that aberrant activity of transforming growth factor ß (TGF-ß) signaling pathway could contribute to the vascular smooth muscle cells' (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of bone morphogenetic protein (BMP)/Smad pathway via a polyubiquitination-dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-ß. Here, we further validated and confirmed the role of Nedd4 in in vivo vascular calcification progression. First, Nedd4 deletion in SM22α-positive mouse tissues (Nedd4fl/fl ;SM22α-Cre) showed deformed aortic structures with disarranged elastin fibers at 24 weeks after birth. Second, vitamin D-induced aorta vascular calcification rate in Nedd4fl/fl ;SM22α-Cre mice was significantly higher than their wild-type littermates. Nedd4fl/fl ;SM22α-Cre mice showed a development of vascular calcification even at very low-level injection of vitamin D, but this was not exhibited in wild-type littermates. Third, we confirmed that TGF-ß1-induced pSmad1 levels were elevated in Nedd4-deficient primary VSMCs isolated from Nedd4fl/fl ;SM22α-Cre mice. Fourth, we further found that Nedd4fl/fl ;SM22α-Cre mVSMCs gained mesenchymal cell properties toward osteoblast-like differentiation by a stable isotope labeling in cell culture (SILAC)-based proteomics analysis. Finally, epigenetic analysis revealed that methylation levels of human NEDD4 gene promoter were significantly increased in atherosclerosis patients. Collectively, abnormal expression or dysfunction of Nedd4 E3 ligase could be involved in vascular calcification of VSMCs by activating bone-forming signals during atherosclerosis progression. © 2016 American Society for Bone and Mineral Research.

Postural stability in patients with anterior cruciate ligament tears with and without medial meniscus tears.

PURPOSE: To compare postural stability in patients with isolated anterior cruciate ligament (ACL) tears and ACL tears with associated meniscal tears. METHODS: Quadriceps and hamstring muscle strength and their ratio, as well as the relationships of these parameters with postural stability, were compared in 23 patients with isolated ACL tears and 27 with combined ACL and medial meniscus tears. Postural stability was determined from the anterior-posterior, medial-lateral, and overall stability indices using the Biodex Stability System. RESULTS: On both the involved and uninvolved sides, there were no differences in mean stability indices, including anterior-posterior, medial-lateral, and overall stability indices, in patients with isolated and combined ACL tears. In patients with isolated ACL tears, both overall (2.3 ± 1.2 vs. 1.8 ± 1.4, p = 0.033) and medial-lateral (1.2 ± 0.6 vs. 1.0 ± 0.5, p = 0.031) stability indices were significantly higher on the involved compared to the uninvolved side. These differences, however, were not observed in the combined ACL tear group. CONCLUSION: No significant differences in postural instability on the affected and unaffected sides were observed in patients with isolated ACL tears and those with combined ACL and medial meniscus tears. These findings indicate that there is no need to reduce the goal of restoring proprioception in patients with combined compared with isolated ACL tears. LEVEL OF EVIDENCE: III.

Is the critical pathway effective for the treatment of gastric cancer?

PURPOSE: The present study was conducted to investigate the low compliance rate of the critical pathway (CP) and whether CP is effective for treatment of gastric cancer in radical gastrectomy. METHODS: The medical records of 631 patients who had undergone radical gastrectomy with D2 lymph node dissection were reviewed. This study compared data from patients in early gastric cancer (EGC) and advanced gastric cancer (AGC) groups, which were further subdivided into general care (non-CP) and CP groups. RESULTS: The mean length of preoperative hospital stays were significantly different between the EGC and AGC patients (P < 0.05). However, there was no difference in the mean length of postoperative hospital stays between non-CP and CP groups among either EGC patients or AGC patients (P > 0.05). The postoperative and total cost of hospitalization was not statistically different between either of the groups (P > 0.05); however, the mean preoperative costs were significantly different (P < 0.05). CONCLUSION: We conclude that use of the CP following gastrectomy is unnecessary. To decrease the length of hospital stay and associated costs, preoperative examination and consultation should be performed before admission.

Prealbumin levels as a useful marker for predicting infectious complications after gastric surgery.

BACKGROUND/OBJECTIVES: Preoperative nutritional status is associated with postoperative complications. Prealbumin, a visceral protein, is sensitive to protein malnutrition. The objective of this study is to evaluate the role of preoperative prealbumin levels as a marker for predicting complications after gastric surgery. METHODS: An observational study was performed on 183 patients who underwent gastric surgery due to benign or malignant gastric disease at Seoul National University Hospital (SNUH) between August 2009 and October 2010. Preoperative prealbumin levels were also measured. Nutritional variables such as prealbumin (cutoff value, 18 mg/dL), albumin, body mass index (BMI), and clinicopathologic data were collected. Postoperative hospital stay, 30-day complications and mortality rate were obtained to investigate outcomes. RESULTS: The complication rate was 52% in the abnormal prealbumin group (n = 23) and 24% in the normal prealbumin group (n = 160; p = 0.005). The complication rate was higher in patients with low preoperative albumin levels (<3.5 g/dL) and abnormal BMI (<18.5 kg/m(2)), but the differences were not statistically significant. Comorbidity of diabetes mellitus (DM), resection extent, combined resection, TNM stage and prealbumin levels were associated with complications. In multivariate analysis, DM and combined resection were significantly correlated with complications (p = 0.001 for each). In subgroup analysis, resection extent, approach, combined resection, TNM stage, and prealbumin levels were significantly associated with infectious complications. Multivariate analysis identified combined resection (p = 0.001) and prealbumin levels (p = 0.032) as independent variables. CONCLUSIONS: Preoperative prealbumin levels could be a useful marker for predicting complications, especially infectious complications, after gastric surgery.

Increased morbidity rates in patients with heart disease or chronic liver disease following radical gastric surgery.

BACKGROUND: The aim of this study was to investigate possible associations between (i) comorbid disease and (ii) perioperative risk factors and morbidity following radical surgery for gastric cancer. MATERIALS AND METHODS: Consecutive patients (759) undergoing radical gastrectomy and D2 level lymph node dissection for gastric cancer were included. Clinical data concerning patient characteristics, operative methods, and complications were collected prospectively. RESULTS: The morbidity rate for radical gastrectomy was 14.2% (108/759). The most significant comorbid risk factors for postoperative morbidity were heart disease [anticoagulant medication: OR = 1.5 (95% CI = 0.35-6.6, P = 0.53); history without medication: OR = 4.0 (95% CI = 1.1-14.6, P = 0.03); history with current medication: OR = 6.7 (95% CI = 1.5-29.9, P = 0.01)] and chronic liver disease [chronic hepatitis: OR = 2.4 (95% CI = 0.9-6.5, P = 0.07); liver cirrhosis class A: OR = 8.4 (95% CI = 2.8-25.3, P = 0.00); liver cirrhosis class B: OR = 9.38 (95% CI = 0.7-115.5, P = 0.08)]. The most significant perioperative risk factors for postoperative morbidity were high TNM stage and combined organ resection (P < 0.05), and there was no association between increased postoperative morbidity and well controlled hypertension, anticoagulant therapy, diabetes mellitus, pulmonary disease, tuberculosis, or thyroid disease (P > 0.05). CONCLUSION: Patients with heart disease or chronic liver disease are at a higher risk of morbidity following radical surgery for gastric cancer.

Synchronous and metachronous cancers in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: The purpose of this study is to investigate characteristics of synchronous and metachronous cancer in gastric cancer and to suggest appropriate methods of treatment management. METHODS: We reviewed 4,593 patients who underwent operations for gastric cancer at Seoul National University Hospital from 1999 to 2005. We selected those patients who had also been diagnosed with another primary cancer and classified patients into three groups according to the date of detection of another primary cancer. We analyzed their clinicopathological features. RESULTS: The incidence of synchronous or metachronous cancer in addition to gastric cancer was 3.4%. The most common another primary cancer was colorectal cancer (20.1%), followed by lung cancer and liver cancer. The majority of synchronous cancers were operated on at the same time as gastric cancer. Eighty-five percent of the synchronous group and 45% of the post-metachronous group were detected by a routine checkup, without prior symptoms. There was no postoperative mortality and the overall 5-year survival rate was 69.4%. CONCLUSION: Synchronous cancer should be considered in the preoperative workup and combined resection should be applied whenever possible. Periodic examination for metachronous cancer is necessary during the postoperative period.

Electrospinning of collagen nanofibers: effects on the behavior of normal human keratinocytes and early-stage wound healing.

Electrospinning of type I collagen in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) to fabricate a biomimetic nanofibrous extracellular matrix for tissue engineering was investigated. The average diameter of collagen nanofibers electrospun from 8% collagen solution in HFIP was 460 nm (range of 100-1200 nm). The as-spun collagen nanofibrous matrix was chemically cross-linked by glutaraldehyde vapor with a saturated aqueous solution and then treated with aqueous 0.1m glycine to block unreacted aldehyde groups. With vapor phase cross-linking for 12h, porosity of the collagen matrix decreased from 89% to 71%. The collagen nanofibrous matrix showed good tensile strength, even in aqueous solution. Effects on cytocompatibility, cell behavior, cell and collagen nanofiber interactions, and open wound healing in rats were examined. Relatively low cell adhesion was observed on uncoated collagen nanofibers, whereas collagen nanofibrous matrices treated with type I collagen or laminin were functionally active in responses in normal human keratinocytes. Collagen nanofibrous matrices were very effective as wound-healing accelerators in early-stage wound healing. Our results indicate that cross-linked collagen nanofibers coated with ECM proteins, particularly type I collagen, may be a good candidate for biomedical applications, such as wound dressing and scaffolds for tissue engineering.

Analysis of the functional integrity of cryopreserved human liver cells including xenografting in immunodeficient mice to address suitability for clinical applications.

BACKGROUND: The availability of well-characterized human liver cell populations that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after cryopreservation and engraft in immunodeficient mice. METHODS: We isolated cells from discarded human livers and studied the properties of cryopreserved cells. The viability of thawed cells was established with multiple in vitro assays, including analysis of liver gene expression, ureagenesis, cytochrome P450 activity, and growth factor-induced cell proliferation. The fate of transplanted cells was analysed in immunodeficient NOD-SCID mice. RESULTS: After thawing, the viability of human hepatocytes exceeded 60%. Cells attached to culture dishes, proliferated following growth factor stimulation and exhibited liver-specific functions. After transplantation in NOD-SCID mice, cells engrafted in the peritoneal cavity, a heterologous site, as well as the liver itself, retained hepatic function and proliferated in response to liver injury. Transplanted hepatocytes were integrated in the liver parenchyma. Occasionally, transplanted cells were integrated in bile ducts. CONCLUSIONS: Cryopreserved human liver cell showed the ability to retain functional integrity and to reconstitute both hepatic and biliary lineages in mice. These studies offer suitable paradigms aimed at characterizing liver cells prior to transplantation in people.

Enzymatically labeled chromosomal probes for in situ identification of human cells in xenogeneic transplant models.

Analysis of the viability, differentiation, clonogenicity and function of human stem/progenitor cells requires suitable xenograft models. However, the identification of transplanted cells has been generally difficult. Fluorescence in situ hybridization is a tedious method for analyzing tissues, and localization of transplanted cells with X or Y chromosome probes is limited by the sparse signals produced. Therefore, we examined the possibility of generating either pan-nuclear signals with a total human DNA probe or multiple nuclear signals with a pan-centromeric human DNA probe. The probes were labeled with digoxigenin to make reaction products visible by light microscopy and to allow the use of immunohistochemistry methods incorporating various color schemes to demonstrate specific properties of transplanted cells. The ability to localize all types of nucleated human cells with such probes will facilitate studies of stem cell biology and cell and gene therapy, as well as the development of new animal models.