Deterioration After Surgery for Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

STUDY DESIGN: A Prospective cohort study. OBJECTIVE: To investigate the incidence, etiology, and outcomes of patients who experience neurological deterioration after surgery for Degenerative Cervical Myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Postoperative neurological deterioration is one of the most undesirable complications that can occur after surgery for DCM. METHODS: We analyzed data from the Canadian Spine Outcomes and Research Network DCM prospective cohort study. We defined postoperative neurological deterioration as any decrease in modified Japanese Orthopaedic Association (mJOA) score by at least one point from baseline to three months after surgery. Adverse events were collected using the Spinal Adverse Events Severity protocol. Secondary outcomes included patient-reported pain, disability, and health-related quality of life. RESULTS: Among a study cohort of 428 patients, 50 (12%) deteriorated by at least one mJOA point after surgery for DCM (21 by one point, 15 by two points, and 14 by three points or more). Significant risk factors included older age, female sex, and milder disease. Among those who deteriorated, 13 experienced contributing intraoperative or postoperative adverse events, six had alternative non-DCM diagnoses, and 31 did not have an identifiable reason for deterioration. Patients who deteriorated had significantly lower mJOA scores at one year after surgery [13.5 (SD 2.7) vs. 15.2 (SD 2.2), P <0.01 and those with larger deteriorations were less likely to recover their mJOA to at least their preoperative baseline, but most secondary measures of pain, disability, and health-related quality of life were unaffected. CONCLUSIONS: The incidence of deterioration of mJOA scores after surgery for DCM was approximately one in 10, but some deteriorations were unrelated to actual spinal cord impairment and most secondary outcomes were unaffected. These findings can inform patient and surgeon expectations during shared decision-making, and they demonstrate that the interpretation of mJOA scores without clinical context can sometimes be misleading.

Impact of Spinal Manipulation on Lower Extremity Motor Control in Lumbar Spinal Stenosis Patients: A Small-Scale Assessor-Blind Randomized Clinical Trial.

OBJECTIVE: The purpose of this study was to quantify the impact of a single lumbar spinal manipulation (SM) intervention on the leg movement performance of degenerative lumbar spinal stenosis (LSS) patients in a small-scale registered randomized clinical trial. METHODS: Participants with LSS (n = 14) were tested at baseline for pain, lumbar range of motion, and behavioral or kinematic motor performance (using an established Fitts' Law foot-pointing task), then underwent covariate adaptive randomization to receive SM or no intervention. Postintervention all dependent measures were repeated. Experimenters were blinded to patient group allocation. University ethics board approval was attained. RESULTS: For the primary outcome movement time, there was no significant difference between groups. As predicted by Fitts' Law, all participants had longer movement times as task difficulty increased. Secondary kinematic outcomes yielded no significant between-group differences. Consistent with Fitts' Law, kinematic measures changed significantly with task difficulty. Pairwise comparisons revealed the kinematic variables were more adversely affected by greater movement amplitudes than target size changes. No exploratory differences in pain or lumbar range of motion were observed. CONCLUSION: Changes in motor performance were not observed in this chronic pain population after a single SM intervention compared with a control group. Given the sample size, the study may have been underpowered to detect meaningful differences. Fitts' Law was observed for the lower extremity-pointing task for an LSS population and may provide an objective measure of motor performance.

An update on vitamin D for clinicians.

PURPOSE OF REVIEW: The clinical benefits of vitamin D therapy have received substantial attention over the past decade. Recently, several trials looked to clarify the optimal vitamin D dose or serum level needed to promote human health. The purpose of this review is to highlight selected studies published since January 2015. RECENT FINDINGS: Several recent trials challenge whether serum vitamin D levels at least 30 ng/ml promote human health. In postmenopausal women with 25-hydroxyvitamin D [25(OH)D] levels 21 ±â€Š3 ng/ml, high-dose vitamin D for 1 year increased calcium absorption by 1%, without changes in bone mineral density, physical function, or falls when compared with low-dose vitamin D and placebo. High-dose vitamin D increased risk of falling in 200 adults 78 ±â€Š5 years old with baseline 25(OH)D levels of ∼19 ±â€Š9 ng/ml. High-dose vitamin D in adults increased the number and duration of upper respiratory tract infections compared with placebo. Asthma patients achieving 25(OH)D levels more than 30 ng/ml during a trial experienced more respiratory infections than those not achieving such levels. SUMMARY: Recent studies are congruent with the Institute of Medicine's conclusion that humans are vitamin D replete when their serum 25(OH)D levels are at least 20 ng/ml. Higher levels seem to promote falls and respiratory infections.

Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial.

IMPORTANCE: Experts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health. OBJECTIVE: To compare the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density, Timed Up and Go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled clinical trial was conducted at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013, and the final visit was completed on August 8, 2014. A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied. INTERVENTIONS: Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL. MAIN OUTCOMES AND MEASURES: Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed Up and Go and five sit-to-stand tests, functional status (Health Assessment Questionnaire), and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of P values to control for the false discovery rate. RESULTS: After baseline absorption was controlled for, calcium absorption increased 1% (10 mg/d) in the high-dose arm but decreased 2% in the low-dose arm (P = .005 vs high-dose arm) and 1.3% in the placebo arm (P = .03 vs high-dose arm). We found no between-arm changes in spine, mean total-hip, mean femoral neck, or total-body bone mineral density, trabecular bone score, muscle mass, and Timed Up and Go or five sit-to-stand test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity, or functional status. CONCLUSIONS AND RELEVANCE: High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass, or falls. We found no data to support experts' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00933244.

Discovery and in vivo evaluation of dual PI3Kß/δ inhibitors.

Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kß/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kß and δ isoforms in the treatment of a number of inflammatory diseases.

Enhanced inhibition of Listeria monocytogenes by a combination of cold pressed terpeneless Valencia orange oil and antibiotics.

This study was designed to evaluate the ability of cold pressed terpeneless Valencia orange oil (CPTVO) to enhance the effectiveness of antibiotics against 10 strains of Listeria monocytogenes. Disc diffusion assays were performed to determine the effects of CPTVO and two antibiotics with different mechanisms of action (i.e., penicillin and chloramphenicol) individually and in combination with CPTVO. CPTVO alone produced zones ranging from 16.5 to 19.9 mm. Penicillin at 2 or 10 units produced zones ranging from <6 to 13.4 mm, and from 16 to 19.5 mm, respectively. Chloramphenicol at 5 or 30 µg had zones ranging from <6 to 6.9 mm, and from 10.8 to 15.9 mm, respectively. Penicillin (2 and 10 units) plus CPTVO produced zones ranging from 20.2 to 25.3 mm, and from 21.9 to 28 mm, respectively. Chloramphenicol (5 or 30 µg) plus CPTVO produced zones of from 20.1 to 26.6 mm, and from 19.5 to 23.9 mm, respectively. In conclusion, the combination of antibiotics with CPTVO increases their ability to inhibit L. monocytogenes.

Inhibition of Listeria monocytogenes by exposure to a combination of nisin and cold-pressed terpeneless Valencia oil.

Listeria monocytogenes is an important foodborne pathogen and its control in foods is a significant challenge. This study evaluated the effectiveness of nisin and cold-pressed terpeneless Valencia oil (CPTVO) on limiting L. monocytogenes growth. Disk diffusion assays were performed to determine the effects of CPTVO and nisin individually and in combination. Together, these antimicrobials produced a zone of inhibition that was significantly larger (P < 0.05) than zones correlating to CPTVO or nisin individually. Furthermore, L. monocytogenesΔsigB had an increased sensitivity to the combination treatment. Growth experiments performed in brain heart infusion (BHI) broth revealed the effects of nisin and CPTVO, individually and in combination on L. monocytogenes growth rate. When L. monocytogenes was grown in BHI containing 0.025% CPTVO and 26 IU/mL nisin, no growth inhibition was observed relative to the control. However, exposure to CPTVO at 0 h followed by the introduction of nisin at 15 h resulted in a statistically significant (P < 0.05) reduction in growth. This approach to inhibiting L. monocytogenes has potential as an all-natural, generally-recognized-as-safe multiple hurdle intervention that may be applicable for ready-to-eat products in which L. monocytogenes is likely to cause foodborne illness.

Electrostatic sprays of food-grade acids and plant extracts are more effective than conventional sprays in decontaminating Salmonella Typhimurium on spinach.

About 40000 people fall victim to Salmonella infections every year in the United States. Recent occurrences of Salmonella contaminated spinach and its recalls have accelerated the need for efficient antimicrobials targeting these pathogens. Our study was aimed at evaluating the inhibitory properties of malic, tartaric, and lactic acids, and grape seed extract (GSE) alone and in combinations and their application methods against Salmonella Typhimurium-inoculated spinach using a response surface method. Fresh spinach leaves were washed, disinfected with sodium hypochlorite solution (0.04% v/v), rewashed with sterile deionized (DI) water, and inoculated with a 2nd-day culture of S. Typhimurium (7.0 log CFU/mL). Adhered S. Typhimurium population on day 0 were 7.5 log CFU/g. These were treated with individual and combinations of organic acids with GSE or DI water (control) adjusted to the same pH as that of the test solutions with both the modes of application and leaves were refrigerated at 4 °C. Malic acid (2%) in combination with GSE (3%) or lactic acid (3%) sprayed electrostatically showed reductions of 2.6 to 3.3 log CFU/g compared to lower log reductions (0.0 to 0.3 log CFU/g) by day 14 if sprayed conventionally. These findings indicate that malic acid in combination with GSE/lactic acid solutions applied by electrostatic spraying exhibited higher inhibition of pathogens than conventional spraying and can be used for commercial applications to enhance food safety.

Campylobacter and Arcobacter species sensitivity to commercial orange oil fractions.

Seven orange oil fractions were screened for their ability to inhibit the growth of selected Campylobacter and Arcobacter spp. using the standard agar-disk diffusion assay. Cold pressed (CP) terpeneless Valencia orange oil was found to be the most inhibitory to both Campylobacter jejuni and Campylobacter coli, exhibiting maximum zones of inhibition up to 80+/-0.0 mm. Five-fold concentrated Valencia oil and distilled d-limonene resulted in Campylobacter inhibition zones ranging from 11.0+/-1.4 to 44+/-1.4 mm against both C. jejuni and C. coli. No inhibition of Arcobacter spp. was detected by 6 out of 7 orange fractions except CP terpeneless Valencia orange oil which produced inhibition zones varying from 9.5+/-0.7 to 29+/-1.4 mm. Naturally occurring C. jejuni UAF 244 was isolated from a whole retail chicken, confirmed by hippuricase gene PCR assay, and used to determine antimicrobial capacities of the CP terpeneless Valencia orange oil and limonene when applied on chicken legs and thighs. The two types of chicken parts did not influence the antimicrobial strength of both orange fractions. While the observed reduction of C. jejuni cells attached to the skin varied approximately 1.5 to 2 logarithms compared to the control, the growth inhibition of the bacterial cells by limonene in the rinse increased by 6-fold and complete inhibition without recovery of detectable viable cells occurred when CP Valencia orange oil was applied. The study demonstrated the potential of the selected commercial orange oil fractions to serve as natural antimicrobials against C. jejuni, C. coli, and Arcobacter spp.