New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits

Promoting new bone formation during distraction osteogenesis (DO) in elderly patients with osteoporosis is still a challenge. In this study, we investigated the effect of gene therapy using local Runt‐related gene 2 on new bone formation during osteoporotic mandibular DO in rabbits. First, we successfully established a mandibular osteoporotic animal model by ovariectomizing rabbits. Second, the right mandibles of the osteoporotic rabbits were distracted after corticotomy. The distraction gap of the rabbits in Group A2 and B2 were injected with Adv‐hRunx2‐GFP‐transfected adipose‐derived stromal cells (ADSCs) and Adv‐GFP‐transfected ADSCs, respectively. Rabbits in Groups C2 (ovariectomized control) and D2 (sham surgery control) were injected with physiologic saline. New‐generation bone tissue in the distraction gap was analyzed via plain radiographic examinations, micro‐computed tomography, histological examinations, and biomechanical testing at weeks 3, 6, and 9 of the consolidation period. Results of above examinations showed that no ideal new bone formation was observed in Groups B2 and C2, but obvious ideal new bone formation was observed in Group A2 and D2. The results suggested that gene therapy using rhRunx2‐modified ADSCs promoted new bone formation during osteoporotic mandibular DO and effectively compensated for the detrimental effects of systemic osteoporosis on new bone formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:709–720, 2014.     

Failure to Achieve Normal Metabolic Response in Non-Obese Diabetic Mice and Streptozotocin-Induced Diabetic Mice After Transplantation of Primary Murine Hepatocytes Electroporated With the Human Proinsulin Gene (p3MTChins)

Background

A recent study by Chen et al described a therapy for diabetes that involved electroporation of primary hepatocytes with human proinsulin cDNA, p3MTChins. Intrahepatic transplantation of treated hepatocytes into streptozotocin (STZ) murine and porcine models led to euglycemia, weight maintenance, and normal insulin production. We tested the repeatability of their basic experiments and transplantation technique and expanded the study to include an autoimmune model.

Methods

Hepatocytes were isolated from B6 mice, electroporated with p3MTChins, and glucose-challenged or were injected into hepatic or spleen parenchyma of STZ-diabetic B6 and non-obese diabetic mice. Outcomes included survival, serum glucose levels, insulin, and c-peptide release. Untransfected primary hepatocytes and mice transplanted with these cells served as controls.

Results

p3MTChins-hepatocytes secreted insulin during glucose challenge, but glucose levels did not change with increasing glucose concentrations. Direct hepatic injection led to high mortality rates. Mice that underwent intrasplenic injection survived for >50 days (control = 4 days) and had a mild but stable improvement in hyperglycemia. C-peptide in both mouse models was detectable but eventually declined to baseline in the non-obese diabetic mice.

Conclusions

Hepatocytes can be transfected with p3MTChins to produce human insulin but may lack the proper glucose-sensing or complex storage and secretion capabilities that allow for a finely tuned dynamic insulin response. Treatment is subtherapeutic, and p3MTChins-hepatocyte function may not endure in an autoimmune model. Without successful preliminary findings, cell therapy involving electroporation of p3MTChins does not appear to be practical as a therapy for diabetes and may not be a strategy to pursue at this time.     

Peritoneal transport rate,systemic inflammation,and residual renal function determine peritoneal protein clearance in continuous ambulatory peritoneal dialysis patients

Background

Peritoneal protein clearance (Pcl) is related to the mortality of patients on continuous ambulatory peritoneal dialysis (CAPD) as well as technique failure. In this prospective observational study, we aimed to investigate factors associated with the level of Pcl.

Methods

We prospectively enrolled 344 prevalent CAPD patients. A standard peritoneal equilibrium test was conducted for each patient. Baseline demographics, biochemistry, and Pcl were recorded.

Results

The average Pcl of the patients was 97.40 ± 54.14 mL/day. Peritoneal transport level, serum high-sensitivity C-reactive protein (hsCRP), and residual glomerular filtration rate (rGFR) were independently related to Pcl. The standard β values were 0.53, 0.17, and ?0.10, respectively. Moreover, compared with non-diabetic patients, diabetic patients had a non-significantly higher level of Pcl (104.90 ± 48.65 vs. 96.15 ± 54.97 mL/day; P = 0.06).

Conclusion

Continuous ambulatory peritoneal dialysis patients lose a high amount of protein through the peritoneum each day. The Pcl value is positively related to the level of peritoneal transport and hsCRP and negatively related to the rGFR.     

The early and mid-term results of mitral valve repair for mitral regurgitation in children

Purpose

To review the surgical techniques and mid-term results of mitral valve repair in children with moderate or severe mitral regurgitation (MR).

Methods

One hundred and seven children with moderate or severe MR, aged 19.6 ± 8.5 months, were enrolled in this study. The surgical techniques used for mitral valve repair varied according to the mitral valve morphology, and included annuloplasty, annuloplasty ring, cleft closure, reconstruction of the posterior leaflet, etc. The concomitant cardiac anomalies were treated simultaneously. The results of repair were evaluated by transesophageal echocardiography performed during the operation and by serial transthoracic echocardiography performed during the follow-up.

Results

One hundred and six cases had no more than mild regurgitation intraoperatively, whereas only one case had moderate regurgitation. This patient underwent redo repair immediately, and the subsequent regurgitation was trivial. The in-hospital mortality rate was 0.9 % (1/107). The average follow-up was 46.5 ± 8.2 months. One patient died of heart failure 10 months postoperatively. The freedom from moderate or severe regurgitation after mitral valve repair was 92.3 ± 3.3 %.

Conclusion

Pediatric patients with moderate or severe MR require early surgical treatment. The early and mid-term results of mitral valve repair in pediatric patients were satisfactory.     

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind,randomized sham-controlled trial

Persons with Parkinson’s disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD. A total of nine persons with PD (mean age 63.3?±?8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session. Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55–97.5) and a significant Spearman’s correlation with the Flow State Scale (r?=?.762, p?=?.017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT. This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial. Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.     

Pathologic Grade and Tumor Size are Associated with Recurrence-Free Survival in Patients with Duodenal Neuroendocrine Tumors

Background

Duodenal neuroendocrine tumors are rare and few studies exist to guide surgical management. This study identifies factors associated with recurrence after resection.

Methods

A retrospective, single institution review was performed between 1983 and 2011 on patients with a pathologic diagnosis of duodenal neuroendocrine tumor. Tumor grade was assigned based on WHO 2010 criteria (Ki-67 and mitotic rate).

Results

Seventy-five patients were identified that underwent curative resection. This included 12 patients with endoscopic mucosal resection, 34 that had local resection, and 29 that underwent pancreaticoduodenectomy. Two-year and 5-year recurrence-free survival was 84 and 81 %, respectively. There were 11 tumor recurrences (either local or distant), and four patients died of their disease (3/4 had high-grade lesions) with an overall median follow-up of 27 months. On univariate analysis, tumor size and tumor grade were identified as being associated with recurrence, but not intervention type, lymph node metastases, ampullary location, or margin status.

Conclusions

Tumor grade and size are associated with recurrence-free survival in duodenal neuroendocrine tumors. When feasible, a less aggressive surgical approach to treat low-grade and low-stage duodenal NETs should be considered.