The role of oxygen as a regulator of stem cell fate during fracture repair in TSP2‐null mice

It is often difficult to decouple the relative importance of different factors in regulating MSC differentiation. Genetically modified mice provide model systems whereby some variables can be manipulated while others are kept constant. Fracture repair in thrombospondin‐2 (TSP2)‐null mice is characterized by reduced endochondral ossification and enhanced intramembranous bone formation. The proposed mechanism for this shift in MSC fate is that increased vascular density and hence oxygen availability in TSP2‐null mice regulates differentiation. However, TSP2 is multifunctional and regulates other aspects of the regenerative cascade, such as MSC proliferation. The objective of this study is to use a previously developed computational model of tissue differentiation, in which substrate stiffness and oxygen tension regulate stem cell differentiation, to simulate potential mechanisms which may drive alterations in MSC fate in TSP2‐null mice. Four models (increased cell proliferation, increased numbers of MSCs in the marrow decreased cellular oxygen consumption, and an initially stiffer callus) were not predictive of experimental observations in TSP2‐null mice. In contrast, increasing the rate of angiogenic progression led to a prediction of greater intramembranous ossification, diminished endochondral ossification, and a reduced region of hypoxia in the fracture callus similar to that quantified experimentally by the immunohistochemical detection of pimonidazole adducts that develop with hypoxia. This study therefore provides further support for the hypothesis that oxygen availability during early fracture healing is a key regulator of MSC bipotential differentiation, and furthermore, it highlights the advantages of integrating computational models with genetically modified mouse studies for further elucidating mechanisms regulating stem cell fate. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1585–1596, 2013.     

Non-tuberculous mycobacterial PD peritonitis in Australia

Purpose

Peritonitis can be a severe complication of peritoneal dialysis (PD) due to associated morbidity and mortality. Non-tuberculous mycobacteria (NTM) are a rare cause of PD peritonitis, with high rates of catheter removal and conversion to haemodialysis, and a reported mortality as high as 40 %. The incidence, culprit NTM species, and outcomes associated with PD peritonitis have not been described in many countries, including Australia.

Methods

We examined the Australia and New Zealand Dialysis and Transplant Registry from 1 October 2003 to 31 December 2009 for all prevalent peritoneal dialysis patients. Patient characteristics, organisms, treatment and outcome for all NTM PD peritonitis episodes were obtained.

Results

Twelve cases of NTM PD peritonitis were reported, including the first reports of infection due to Mycobacterium hassiacum and Mycobacterium neoaurum. The incidence of NTM PD peritonitis was approximately 1 per 1000 PD patient-years. Recovery occurred in 11 patients, including 3 without removal of their Tenckhoff catheters. A range of antibiotics were utilised. One patient died of sclerosing peritonitis 5 months after diagnosis of PD peritonitis.

Conclusion

Non-tuberculous mycobacteria PD peritonitis is a rare cause of peritonitis, and mortality may be lower than previously reported. Catheter removal occurred in the majority of patients, and adverse outcomes were not observed for those in whom it was retained.     

Outcome of laparoscopic colectomy for cancer in elderly patients

Background

Resection for colon cancer in the elderly is a major undertaking. However, data on the outcome and survival of elderly patients who underwent laparoscopic resection for colon cancer are limited. This study of patients older than 75 years compared outcome and survival between those who underwent laparoscopic resection and those who had open resection for colorectal cancer.

Methods

From 2000 to 2009, 434 patients ages 75 years and older who underwent elective resection for colon cancer were included in the study. Patients who had rectal cancer or had undergone emergency operations were excluded. Preoperative diagnosis was determined by colonoscopy, and computed tomography scan was performed for preoperative staging. Data on the patients’ demographics, operative details, pathology results, postoperative results, and survival were collected prospectively. The patients who underwent laparoscopic surgery were compared with those who had open surgery.

Results

The study included 434 patients (210 men) with a median age of 80 years (range 75–95 years). Of these 434 patients, 189 underwent laparoscopic resection. Nine patients (4.8 %) required conversion to open operation. The patients did not differ in terms of age, gender, incidence of medical comorbidities, or stage of disease. The median operating time was longer in the laparoscopic group, but the blood loss was significantly less. Laparoscopic resection was associated with a lower mortality rate and a shorter hospital stay (p < 0.05). The open resection group had significantly more cardiac complications (p < 0.05). The overall 5-year survival rates were similar between the patients who had laparoscopic resections and those who had open surgery.

Conclusions

For patients older than 75 years, laparoscopic resection of colon is associated with less intraoperative blood loss, a shorter hospital stay, fewer cardiac complication, and a lower mortality rate than open resection. Therefore, the authors recommend laparoscopic resection of colon cancer as the treatment of choice for elderly patients.     

ERCP via gastrostomy vs. double balloon enteroscopy in patients with prior bariatric Roux-en-Y gastric bypass surgery

Background

Roux-en-Y gastric bypass (RYGB) is the most common bariatric surgery. The performance of ERCP in bariatric RYGB is challenging due to the long Roux limb. We herein compared the indications and technical outcomes of ERCP via percutaneous gastrostomy (GERCP) and double balloon enteroscopy (DBERCP) for patients with prior bariatric RYGB anatomy.

Methods

Between December 2005 and November 2011, consecutive ERCP patients who had undergone RYGB were identified using a prospectively maintained electronic ERCP database. Medical records were abstracted for ERCP indications and outcomes. In most cases, the gastrostomy was done by either laparoscopic or open surgery and allowed to mature at least 1 month before performing ERCP. The choice of route for ERCP was at discretion of managing physician.

Results

Forty-four patients (F = 42) with GERCP and 28 patients (F = 26) with DBERCP were identified. The mean age was younger in GERCP than DBERCP (44.8 vs. 56.1, p < 0.001). GERCP patients were more likely to have suspected sphincter of Oddi dysfunction (77 %) as the primary indication whereas DBERCP was suspected CBD stone (57 %). The mean total number of sessions/patient in GERCP and DBERCP was 1.7 ± 1.0 and 1.1 ± 0.4, respectively (p = 0.004). GERCP access to the major papilla was successful in all but two (97 %), whereas duct cannulation and interventions were successful in all. In DBERCP, the success rate of accessing major papilla, cannulation and therapeutic intervention was 78, 63, 56 %, respectively. There was one (3.1 %) post-ERCP pancreatitis in DBERCP. Complications occurred in 11 GERCP procedures (14.5 %) and 10 were related to the gastrostomy. This was significantly higher than that of DBERCP (p = 0.022).

Conclusions

GERCP is more effective than DBERCP in gaining access to the pancreatobiliary tree in patients with RYGB, but it is hindered by the gastrostomy maturation delay and a higher morbidity. Technical improvements in each method are needed.     

Spinal cord injuries related to cervical spine fractures in elderly patients: factors affecting mortality

Background contextSpinal cord injuries (SCIs) related to cervical spine (C-spine) fractures can cause significant morbidity and mortality. Aggressive treatment often required to manage instability associated with C-spine fractures is complicated and hazardous in the elderly population.PurposeTo determine the mortality rate of elderly patients with SCIs related to C-spine fractures and identify factors that contribute toward a higher risk for negative outcomes.Study design/settingRetrospective cohort study at two Level 1 trauma centers.Patient sampleThirty-seven consecutive patients aged 60 years and older who had SCIs related to C-spine fractures.Outcome measuresLevel of injury, injury severity, preinjury medical comorbidities, treatment (operative vs. nonoperative), and cause of death.MethodsHospital medical records were reviewed independently. Baseline radiographs and computed tomography or magnetic resonance imaging scans were examined to permit categorization according to the mechanistic classification by Allen and Ferguson of subaxial C-spine injuries. Univariate logistic regression analyses were performed to identify factors related to in-hospital mortality and ambulation at discharge. There were no funding sources or potential conflicts of interest to disclose.ResultsThe in-hospital mortality rate was 38%. Respiratory failure was the leading cause of death. Preinjury medical comorbidities, age, and operative versus nonoperative treatment did not affect mortality. Injury level at or above C4 was associated with a 7.1 times higher risk of mortality compared with injuries below C4 (p=.01). Complete SCI was associated with a 5.1 times higher risk of mortality compared with incomplete SCI (p=.03). Neurological recovery was uncommon. Apart from severity of initial SCI, no other factor was related to ambulatory disposition at discharge.ConclusionsIn this elderly population, neurological recovery was poor and the in-hospital mortality rate was high. The strongest risk factors for mortality were injury level and severity of SCI. Although each case of SCI related to C-spine fractures is different, physicians may be able to use these findings to help better determine the prognosis and guide subsequent treatment.     

Single high-dose oral vitamin D3 (stoss) therapy — A solution to vitamin D deficiency in children with cystic fibrosis?

ObjectivesTo determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (< 75 nmol/L).Study designRetrospective chart review of 142 paediatric CF patients from 2007 till 2011.ResultsThirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p = 0.001; 81.54 ± 24.6 nmol/L, p = 0.001; 92.18 ± 36.5 nmol/L, p = 0.008 and 64.6 ± 20.0 nmol/L, p = 0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p = 0.038).ConclusionStoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.     

A comparison of surgeon’s postural muscle activity during robotic-assisted and laparoscopic rectal surgery

This study compared the muscular activity in the surgeon’s neck and upper limbs during robotic-assisted laparoscopic (R-Lap) surgery and conventional laparoscopic (C-Lap) surgery. Two surgeons performed the same procedure of R-Lap and C-Lap low anterior resection, and real-time surface electromyography was recorded in bilateral cervical erector spinae, upper trapezius (UT) and anterior deltoid muscles for over 60 min in each procedure. In one surgeon, forearm muscle activities were also recorded during robotic surgery. Similar levels of cervical muscle activity were demonstrated in both types of surgery. One surgeon showed much higher activity in the left UT muscle during robotic surgery. In the second surgeon, C-Lap was associated with much higher levels of muscle activity in both UT muscles. This may be related to the bilateral abducted arm posture required in maneuvering the laparoscopic instruments. In the forearm region, the “ulnaris” muscles for wrist flexion and extension bilaterally showed high amplitudes during robotic-assisted surgery. Robotic-assisted surgery seemed to demand a higher level of muscle work in the forearm region while greater efforts of shoulder muscles were involved during laparoscopic surgery. There are also individual variations in postural habits and motor control that can affect the muscle activation patterns. This study demonstrated a method of objectively examining the surgeon’s physical workload during real-time surgery in the operating theatre, and further research should explore the surgeon’s workload in a larger group of surgeons performing different surgical procedures.