Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, part 1: a phase I and IIa clinical trial

Objective

Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy.

Methods

We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 μg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy.

Results

G-CSF administration suppressed the progression of myelopathy in all 15 patients. Neurological improvements in motor and sensory functions were obtained in all patients after the administration, although the degree of improvement differed among the patients. Nine patients in the 10-μg group (n = 10) underwent surgical treatment at 1 month or later after G-CSF administration. In the 10-μg group, the mean JOA recovery rates 1 and 6 months after administration were 49.9 ± 15.1 and 59.1 ± 16.3%, respectively. On the day following the start of G-CSF therapy, the white blood cell count increased to more than 22,700 cells/mm³. It varied from 12,000 to 50,000 and returned to preadministration levels 3 days after completing G-CSF treatment. No serious adverse events occurred during or after treatment.

Conclusion

The results indicate that G-CSF administration at 10 μg/kg/day is safe for patients with worsening symptoms of compression myelopathy and may be effective for their neurological improvement.     

Etanercept treatment enhances clinical and neuroelectrophysiological recovery in partial spinal cord injury

Purpose

To investigate the effect of an anti-TNF-α agent (etanercept) on recovery processes in a partial spinal cord injury (SCI) model using clinical and electrophysiological tests.

Methods

Twenty-four New Zealand rabbits were divided into three groups: group 1 [SCI + 2 ml saline intramuscular (i.m.), n = 8], group 2 (SCI + 2.5 mg/kg etanercept, i.m., 2–4 h after SCI, n = 8) and group 3 (SCI + 2.5 mg/kg etanercept, i.m., 12–24 h after SCI, n = 8). Rabbits were evaluated before SCI, immediately after SCI, 1 week after, and 2 weeks after SCI, clinically by Tarlov scale and electrophysiologically by SEP.

Results

Tarlov scores of groups 2 and 3 were significantly better than group 1, 2 weeks after SCI. SEP recovery was significantly better in groups 2 and 3 than group 1, 2 weeks after SCI.

Conclusions

These results show that blocking TNF-α mediated inflammation pathway by an anti-TNF-α agent enhances clinical and electrophysiological recovery processes in partial SCI model.     

Electrical stimulation of the urethra evokes bladder contractions and emptying in spinal cord injury men: case studies

Objective

Electrical stimulation of the urethra can evoke bladder contractions in persons with spinal cord injury (SCI). The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions that empty the bladder.

Methods

The first patient was a 45-year-old man with a T6 ASIA A SCI secondary to a gunshot wound 15 years prior. The second patient was a 51-year-old man with a T2 ASIA A SCI secondary to a fall from scaffolding 2 years prior. Both patients demonstrated neurogenic detrusor overactivity on urodynamics and managed their bladder with clean intermittent catheterization and oxybutynin medication. Following informed consent, each patient discontinued oxybutynin 2 days prior to urodynamic testing. Urodynamics were performed with a custom 12 French balloon catheter mounted with ring-shaped electrodes (3 mm) positioned in the prostatic urethra. After filling the bladder to approximately three-fourth of capacity at a rate of 25 ml/minute, the urethra was stimulated with a range of parameters to determine whether electrical stimulation could evoke a bladder contraction and empty the bladder.

Results

Electrical stimulation of the prostatic urethra evoked bladder contractions (peak detrusor pressures of 60–80 cm H₂O) that emptied the bladder in both subjects. In the first subject, stimulation (9–12 mA, 20 Hz) emptied 64–75%, leaving post-void residual volumes (PVRs) of 41–20 ml. In the second subject, stimulation (20 mA, 20 Hz) emptied 68–77%, leaving PVRs of 56–45 ml.

Conclusion

Urethral stimulation evoked bladder emptying in persons with SCI.     

Long-term outcomes of adults with pediatric-onset spinal cord injuries as a function of neurological impairment

Objective

To identify outcomes of participation, life satisfaction, and medical complications as a function of impairment in adults with pediatric-onset spinal cord injury (SCI).

Methods

Study participants were adults who sustained SCI at age 18 years or younger and were interviewed at age 24 years or older (M = 26.9, SD = 3.5). The telephone interview included a questionnaire and several standardized measures: FIM^® instrument (FIM^®), Craig Handicap Assessment and Reporting Technique (CHART), SF-12^® Health Survey, and Satisfaction with Life Scale. Using the International Standards for Neurological Classification of Spinal Cord Injury and the American Spinal Injury Association (ASIA) Impairment Scale (AIS), subjects were grouped into four impairment categories: C1–C4 ABC, C5–C8 ABC, T1–L4 ABC, and AIS D.

Results

Of the 410 participants, 62% were male, 54% had tetraplegia, 70% had AIS A lesions, and average age at injury was 14 years (SD = 4.3). Of the 407 subjects who had complete neurological information, 59 had C1–C4 ABC, 140 had C5–C8 ABC, 168 had T1–L4 ABC, and 40 had AIS D lesions. The outcomes were delineated for education, employment, independent living and driving, marriage, participation, medical complications, health-related quality of life, and global life satisfaction, in addition to the ASIA motor score and FIM^® motor scores, for each of the four impairment groups.

Conclusions

This information should help focus interventions that facilitate positive outcomes in relationship to the severity of impairment. In addition, these data can provide a level of expectation about long-term outcomes for newly injured children and their parents.     

Soleus H-reflex modulation after motor incomplete spinal cord injury: effects of body position and walking speed

Objective:

To examine position-dependent (semireclined to standing) and walking speed–dependent soleus H-reflex modulation after motor incomplete spinal cord injury (SCI).

Participants:

Twenty-six patients with motor incomplete SCI (mean: 45 ± 15 years) and 16 noninjured people (mean: 38 ± 14 years).

Methods:

Soleus H-reflexes were evoked by tibial nerve stimulation. Patients were tested in semireclined and standing positions (experiment 1) and in midstance and midswing positions (experiment 2).

Results:

H-reflexes were significantly greater after SCI in all positions compared with noninjured people (P < 0.05). Position-dependent modulation from semireclined to standing (normally observed in noninjured people) was absent after SCI. In SCI patients, H-reflex modulation was not significantly different at 1.2 m/s compared with 0.6 m/s treadmill walking speed; in noninjured people, H-reflex modulation was significantly greater at 1.2 m/s compared with 0.6 m/s treadmill walking speed. There was a significant positive correlation between modified Ashworth scores, a clinical measure of spasticity and soleus H-reflex amplitudes tested in all positions. A significant negative correlation was also found between H-reflexes in standing and midstance positions and the amount of assistance patients required to walk.

Conclusions:

An improvement in position-dependent and walking speed–dependent reflex modulation after SCI may indicate functional recovery. Future studies will use H-reflex testing to track changes as a result of therapeutic interventions.     

Chitosan Sponges to Locally Deliver Amikacin and Vancomycin: A Pilot In Vitro Evaluation

Background

Open orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and lowering the cost of treatment. Localized drug delivery has the potential to overcome the challenges associated with traditional systemic dosing. A degradable, biocompatible polymer sponge (chitosan) that can be loaded with clinician-selected antibiotics at the point of care would provide the patient and clinician with a desirable, adjunctive preventive modality.

Questions/purposes

We asked (1) if an adaptable, porous chitosan matrix could absorb and elute antibiotics for 72 hours for potential use as an adjunctive therapy to débridement and lavage; and (2) if the sponges could elute levels of antibiotic that would inhibit growth of Staphylococcus aureus and Pseudomonas aeruginosa?

Methods

We fabricated a degradable chitosan sponge that can be loaded with antibiotics during a 60-second hydration in drug-containing solution. In vitro evaluation determined amikacin and vancomycin release from chitosan sponges at six time points. Activity tests were used to assess the release of inhibitory levels of amikacin and vancomycin.

Results

Amikacin concentration was 881.5 μg/mL after 1 hour with a gradual decline to 13.9 μg/mL after 72 hours. Vancomycin concentration was 1007.4 μg/mL after 1 hour with a decrease to 48.1 μg/mL after 72 hours. Zone of inhibition tests were used to verify inhibitory levels of drug release from chitosan sponges. A turbidity assay testing activity of released amikacin and vancomycin indicated inhibitory levels of elution from the chitosan sponge.

Clinical Relevance

Chitosan sponges may provide a potential local drug delivery device for preventing musculoskeletal infections.     

Enhanced migration of human bone marrow stromal cells in modified collagen hydrogels

Purpose

Collagen I hydrogels are widely used as scaffolds for regeneration of articular cartilage defects. We hypothesised that ingrowth might be improved by removing the superficial layer of a compressed hydrogel. The control group consisted of the original unmodified product.

Methods

The migration of human bone marrow stromal cells (hBMSCs) into the hydrogel was evaluated by confocal microscopy. We quantified the DNA concentration of the hydrogel for each group and time point and evaluated the chondrogenic differentiation of cells.

Results

After one week, the detectable amount of cells at the depth of 26–50 μm was significantly higher in the modified matrix (MM) than in the non-modified matrix (NM) (p = 0.011). The maximum depth of penetration was 75 μm (NM) and 200 μm (MM). After three weeks, the maximum depth of penetration was 175 μm (NM) and 200 μm (MM). Likewise, at a depth of 0–25 μm the amount of detectable cells was significantly higher in the MM group (p = 0.003). After 14 days, the concentration of DNA was significantly higher in the samples of the MM than in the control group (p = 0.000). Staining of histological sections and labelling with collagen II antibodies showed that a chondrogenic differentiation of cells in the scaffold can occur during in vitro cultivation.

Conclusions

Removing the superficial layer is essential to ensuring proper ingrowth of cells within the compressed hydrogel. Compressed hydrogels contribute better to cartilage regeneration after surface modification.     

Is it Time for Cementless Hip Resurfacing?

Background

Metal-on-metal bearing with cemented femoral component and cementless acetabular fixation is the current standard in surface replacement arthroplasty (RSA) of the hip. Because of concerns about the long-term survivorship of cemented stems in conventional hip arthroplasty, it seems logical to achieve cementless fixation on the femoral side with RSA.

Questions/Purposes

The goals of this review were to evaluate clinical and radiological data reported from previously published cementless RSA series. In addition, we intend to review author’s preliminary experience with Conserve Plus cementless devices specifically assessing the clinical outcomes, the complications rate, the survivorship, and the metallic ions levels measured in follow-up.

Methods

A references search was done with PubMed using the key words “cementless hip resurfacing”, “cementless hip resurfacing prosthesis”, and “femoral cementless hip resurfacing”. Additionally, the clinical outcomes, the complications rate, the survivorship, and the metallic ions levels were measured in 94 cementless Conserve Plus^© devices in 90 patients (68 males and 22 females) with a mean age of 41.1 years (18–59). Mean follow-up was 13.1 months (8–16).

Results

No revision was performed during the observed follow-up. Neither radiological signs of loosening nor neck narrowing >10% were evident. Chromium and cobalt levels in whole blood samples rose respectively from 0.53 μg/l (0.1–1.7) to 1.7 μg/l (0.6–2.9) and from 0.54 μg/l (0.1–1.4) to 1.98 μg/l (0.1–2.8).

Conclusions

Cementless “fit and fill” femoral-side fixation, which seems to be potentially evolved and design-related, should be considered for future hip-resurfacing device generations.     

Long-term follow-up and metal ion trend of patients with metal-on-metal total hip arthroplasty

Purpose

Long-term studies are required to support the use of metal-on-metal (MoM) bearings in total hip arthroplasty (THA) given the concern about systemic metal ion release and reports of adverse local soft tissue reactions. The purpose of this study was to report the seven to 13-year clinical, radiographic, and metal ion results in patients following MoM THA.

Methods

We studied 163 prostheses after second-generation MoM THA between July 1997 and November 2003. Cobalt and chromium metal ions were collected using whole and analysed by inductively-coupled plasma-mass spectrometry.

Results

The mean follow-up was 8.87 years (range, 7–13 years). Four hips (2.5 %) were revised. The Kaplan-Meier survivorship was 91.3 % for revision for all causes, and 97.5 % when excluding the hips revised for a manufacturer’s defect. Median whole blood cobalt levels peaked at a value of 2.87 μg/L at four years (p < 0.0001 vs. pre-operative) and subsequently decreased to 2.0 μg/L after nine years (p = 0.002 vs. four years). Median chromium levels maximally increased up to 0.75 μg/L after five years (p < 0.0001 vs. pre-operative) and tended to decrease thereafter to values of 0.56 μg/L after seven years.

Conclusions

This seven to 13-year follow-up study indicates that the clinical and radiological results following MoM THA are satisfactory with low revision rates. Cobalt and chromium ion levels peaked at four and five years, respectively, and gradually decreased thereafter.     

Comparison of nutritional intake between individuals with acute and chronic spinal cord injury

Objective

To compare the nutritional intake of patients with acute and chronic spinal cord injury (SCI).

Design

Cross-sectional, observational study.

Setting

Spinal cord unit.

Methods

Twelve in-house patients of a spinal cord unit with acute SCI and paralysis duration of 5.3 ± 2.5 months (acute group) were compared with 12 subjects with chronic SCI (chronic group) with lesion duration of 55.5 ± 21.0 months. All subjects recorded their nutritional intake for 7 days, which was analyzed for intake of energy, proteins, fat, carbohydrates, vitamins, mineral nutrients, fluid, and dietary fiber. Resting energy expenditure (REE) and total body fat were also determined.

Results

The chronic group showed a significantly higher total body fat content compared to the acute group (19.4 ± 3.8 vs. 15.7 ± 4.3%). All other parameters were not significantly different between groups. Both groups ingested excessive fat and insufficient amounts of carbohydrates compared with common nutritional recommendations. Low intakes of vitamins C, D, E, biotin, folic acid, as well as potassium and iron were found.

Conclusions

No differences were found in the nutritional intakes of two comparable groups of subjects with acute and chronic SCI. Independent of lesion duration, subjects with SCI showed considerable deviations from the general accepted nutritional recommendations concerning macro- and micronutrients intake. Professional nutritional education for persons with SCI should start as soon as possible after injury to prevent nutrition-related secondary complications like cardiovascular diseases. Periodic determinations of body fat content and REE combined with a physical activity program might be helpful as well.     

Surgery for pressure ulcers improves general health and quality of life in patients with spinal cord injury

Study Design:

Prospective clinical study.

Background:

Pressure ulcers interfere with the rehabilitation process in patients with spinal cord injury (SCI) and are a significant deterrent to participation in activities that contribute to independent, productive, and satisfying life.

Objective:

To evaluate the effect of surgery for pressure ulcers on general health and quality of life in patients with SCI.

Setting:

Tertiary care center in northern India.

Methods:

Various types of flap surgery were performed on 30 patients with SCI and 32 pressure ulcers (stages III and IV). Outcome was evaluated using general improvement in health (hemoglobin, serum proteins, and general well-being), patient satisfaction, and global quality of life scores (according to the visual analog scale).

Results:

At admission, the mean values of global quality of life, hemoglobin, serum albumin, and total serum proteins were 50.15 (range, 30–65), 8.75 g/dL (range, 6–12 g/dL), 3.12 g/dL (range, 2.9–4.3 g/dL), and 5.21 (range, 5–6.2 g/dL), respectively. At 6-month follow up, mean values of global quality of life score, hemoglobin, serum albumin, and total serum proteins were 87.36 (range, 44–96), 10.85 g/dL (range, 8.2–13.5 g/dL), 3.89 g/dL (range, 3.2–4.5 g/dL), and 6.43 g/dL (range, 5.85–6.70 g/dL), respectively. The overall rise in quality of life scores, hemoglobin, serum albumin, and total serum proteins was statistically significant. Most of the patients (76.7%) reported improvement in subjective well-being, and 83.3% were satisfied with the ultimate outcome of the surgery.

Conclusion:

Results suggest that surgery for stages III and IV pressure ulcers offers the greatest benefit to the patients in terms of improvement in general health (anemia, hypoproteinemia, and general well-being) and quality of life.     

Psychosocial outcomes among youth with spinal cord injury by neurological impairment

Objective

Examine psychosocial outcomes of youth with spinal cord injury (SCI) as a function of neurological level (paraplegia/tetraplegia) and severity (American Spinal Injury Association (ASIA) Impairment Scale (AIS)).

Design

Survey research.

Setting

Three pediatric SCI specialty centers in the USA.

Participants

Youth with SCI ages 5–18 with neurological impairment classifications of: tetraplegia AIS ABC (tetraplegia ABC), paraplegia AIS ABC (paraplegia ABC), or AIS D.

Outcome Measures

Children''s Assessment of Participation and Enjoyment, Pediatric Quality of Life Inventory, Revised Children''s Manifest Anxiety Scale, and Children''s Depression Inventory.

Results

Three hundred and forty youth participated; 57% were male; 60% were Caucasian, 21% Hispanic, 7% African-American, 2% Native American, and 3% reported “other”. Their mean age was 8.15 years (standard deviation (SD) = 5.84) at injury and 13.18 years (SD = 3.87) at interview. Ninety-six youth (28%) had tetraplegia ABC injuries, 191 (56%) paraplegia ABC injuries, and 53 (16%) AIS D injuries. Neurological impairment was significantly related to participation and quality of life (QOL). Specifically, youth with paraplegia ABC and AIS D injuries participated in more activities than youth with tetraplegia ABC (P = 0.002; P = 0.018, respectively) and youth with paraplegia ABC participated more often than youth with tetraplegia ABC (P = 0.006). Youth with paraplegia ABC reported higher social QOL than youth with tetraplegia ABC (P = 0.001) and AIS D injuries (P = 0.002). Groups did not differ regarding mental health.

Conclusion

Interventions should target youth with tetraplegia ABC, as they may need support in terms of participation, and both youth with tetraplegia ABC and AIS D injuries in terms of social integration.     

Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats

Background:

Oxidative stress is a mediator of secondary injury to the spinal cord following trauma.

Objective:

To investigate the putative neuroprotective effect of α-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI).

Methods:

Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique.

Results:

SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged.

Conclusion:

The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.     

Elevated leptin expression in rat model of traumatic spinal cord injury and femoral fracture

Background

Few studies have reported a relationship between leptin induced by spinal cord injury (SCI) and healing bone tissue.

Objective

To observe serum and callus leptin expression within the setting of fracture and traumatic SCI.

Methods

Seventy-two male Sprague Dawley rats were randomized equally into four groups: control, SCI group, fracture group, and fracture/SCI group. Rats were sacrificed at 7, 14, 21, and 28 days post-fracture/SCI. Serum leptin was detected using radioimmunoassay at 1, 7, 14, 21, and 28 days, and callus formation was measured radiologically at 14, 21, and 28 days. Callus leptin was analyzed by means of immunohistochemistry.

Results

Serum leptin in the fracture group, SCI group, and combined fracture/SCI group were all significantly increased compared to control group at the 1, 7, 14, and 2-day time points (P < 0.05). Serum leptin in the combined fracture/SCI group was significantly higher than in the fracture group at 7, 14, and 21 days (P < 0.05), and higher than in SCI groups at 14 and 21days after operation (P < 0.05). The percentage of leptin-positive cells in the fracture/SCI callus, and callus volume was significantly higher than in the fracture-only group (P < 0.001).

Conclusions

Overall, elevated leptin expression was demonstrated within healing bone especially in the 21 days of a rat model combining fracture and SCI. A close association exists between leptin levels and the degree of callus formation in fractures.     

Antimicrobial Distribution From Local Delivery Depends on Dose

Background

Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement.

Questions/purposes

We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.

Methods

A 1-cm³ soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 μg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA.

Results

The volume of tissue with more than 14 μg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p = 0.02) (2121 mm³ for 10 g and 665 mm³ for 1 g) and smaller with time for the 10-g formulation (2121 mm³ on Day 7 and 1241 mm³ on Day 14).

Conclusions

Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time.

Clinical Relevance

For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.     

Effectiveness of local cooling for enhancing tissue ischemia tolerance in people with spinal cord injury

Objective

To investigate the effects of localized cooling and cooling rate on pressure-induced ischemia for people with and without neurological deficits.

Design

A 2 × 3 mixed factorial design with two groups: (1) people with spinal cord injury (SCI) and (2) people without neurological deficits (control), and three test conditions: (1) pressure only, (2) pressure with fast cooling (−4°C/min), and (3) pressure with slow cooling (−0.33°C/min).

Setting

University laboratory.

Participants

Fourteen controls and 14 individuals with SCI.

Interventions

Pressure on the sacrum was 0.4 kPa for 5 minutes, then 8 kPa for 20 minutes, and finally 0.4 kPa for 15 minutes. Fast and slow cooling to 25°C applied during 8 kPa of pressure.

Outcome measures

Reactive hyperemia and its spectral densities in the metabolic, neurogenic, and myogenic frequency ranges.

Results

In controls, reactive hyperemia was greater in pressure only as compared with both cooling conditions. No change was noted in all spectral densities in both cooling conditions, and only neurogenic spectral density increased without cooling. In subjects with SCI, no difference was noted in reactive hyperemia among conditions. However, metabolic and myogenic spectral densities increased without cooling and all spectral densities increased with slow cooling. No change was noted in all spectral densities with fast cooling.

Conclusion

Local cooling reduced the severity of ischemia in controls. This protective effect may be masked in subjects with SCI due to chronic microvascular changes; however, spectral analysis suggested local cooling may reduce metabolic vasodilation. These findings provide evidence towards the development of support surfaces with temperature control for weight-bearing soft tissues.     

Voriconazole Is Cytotoxic at Locally Delivered Concentrations: A Pilot Study

Background

Fungal infections are rare but major problems when they involve orthopaedic implants. Preferred treatment in North America is two-staged: resection and then delayed reconstruction, with local delivery of an antifungal between stages. The effect of voriconazole, a hydrophobic antifungal, on local tissues and wound healing is unclear.

Questions/purposes

We asked: (1) Is voriconazole cytotoxic to fibroblasts or osteoblasts at target concentrations for local delivery? And (2) if cytotoxic, can fibroblasts or osteoblasts resume proliferation after voriconazole is removed?

Methods

We exposed 5000 fibroblasts or osteoblasts/well to voriconazole concentrations of 0, 1, 5, 10, 25, 100, 500, 1000, 5000, 10,000, and 20,000 μg/mL (n = 4 wells/concentration) in 24-well plates. At 3 and 7 days, cell growth was assessed with alamarBlue^® and light microscopy. After Day 7, exposure to voriconazole was stopped and incubation continued for 4 days in medium with no voriconazole. On Day 11, cell growth (recovery) was assessed with alamarBlue^® and light microscopy.

Results

Increasing voriconazole concentration to more than 100 μg/mL decreased osteoblast and fibroblast growth. Cell growth recovered after 7 days’ exposure to 1000 μg/mL or less.

Conclusions

Voriconazole is cytotoxic to osteoblasts and fibroblasts, but cell growth recovers over 4 days after exposure to 1000 μg/mL or less.

Clinical Relevance

Cytotoxicity seen from voriconazole to mouse osteoblasts and fibroblasts occurs at concentrations achievable clinically from local delivery. It may be prudent to limit the dose of voriconazole in antibiotic-loaded bone cement.     

Assessing the feasibility of subepidermal moisture to predict erythema and stage 1 pressure ulcers in persons with spinal cord injury: a pilot study

Background

Persons with spinal cord injury (SCI) are at high risk for pressure ulcers (PrUs) throughout their lifetime due to decreased mobility, lack of sensation, and other physiological changes. The high prevalence and recurrence rates, and costs associated with PrUs in veterans with SCI indicate the need for a reliable and practical method of detecting early PrUs.

Objective

To assess the feasibility of obtaining biophysical measures of sub-epidermal moisture (SEM) using a handheld dermal phase meter to predict PrUs.

Design/methods

Prospective observational design. Thirty-four veterans at two VA SCI centers (Hines, Long Beach) received daily (n = 12) or weekly (n = 22) SEM and concurrent visual skin assessment (VSA) across nine anatomic locations for up to 6 weeks.

Outcome measures

SEM, visual skin assessment (VSA), and stage I PrUs.

Findings/results

SEM was lowest for normal skin (39.3 dermal phase units (DPU), SD = 12.6) and higher for erythema/stage 1 PrUs (40.8 DPU, SD = 10.4) across all anatomic sites. Buttocks SEM were different between normal skin (40.5 DPU, SD = 10.3) and erythema/stage1 PrUs (43.8, SD = 9.5). SEM taken at heels were lower across all skin conditions (normal skin 28.2 DPU; erythema/stage 1 PrUs 34.7 DPU). SEM was taken when generalized edema present was lower than without generalized edema.

Conclusions

Preliminary results of using SEM to detect early PrU damage may translate from nursing home (NH) residents to persons with SCI. This study provides a foundation for a larger study to implement and assess SEM use as a method of prevention of PrUs.