- Anderson MA, Burda JE, Ren Y, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 2016;532(7598):195–200. doi:10.1038/nature17623.
This is an important paper to be aware of: Astrocytic scars have been regarded as barriers to central nervous system axon regrowth since around 1952. Through an impressive set of experiments, the authors show that using three genetically targeted loss-of-function manipulations in adult mice that prevent scar formation or stop scar forming astrocytes all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. Specifically, they 1) prevented astrocyte scar formation, 2) attenuating scar-forming astrocytes, and 3) ablated chronic astrocytic scars (using genetically targeted diphtheria toxin receptor and ultra-low doses of diphtheria toxin). They conclude that these experiments show that contrary to the prevailing dogma, astrocytic scar formation is not a principal cause for the failure of injured mature CNS axons to regrow across severe CNS lesions. In fact, scar-forming astrocytes permit and support robust amounts of appropriately stimulated CNS axon regeneration. These findings have obvious important implications for CNS repair strategies.
- Liddelow SA, Barres BA. Regeneration: Not everything is scary about a glial scar. Nature. 2016;532(14 April):182–183. doi:10.1038/nature17318.
This is an Editorial that goes along with the previous paper by Anderson et al. How do we reconcile previous experiments showing scar is bad with this current information? One potential answer is that other inhibitory cell types such as fibroblasts and pericytes, also contribute to the glial scar. Other studies have identified different types of reactive astrocyte. Perhaps in the previous studies different types of injury produced different types of reactive astrocyte, some being inhibitory and others not so much. They conclude that “ in spite of long-held beliefs to the contrary, reactive astrocytes may not be the villains of spinal-cord recovery, but instead might provide new hope for the regeneration of damaged axons.”
- Cuellar JM, Stauff MP, Herzog RJ, Carrino JA, Baker GA, Carragee EJ. Does provocative discography cause clinically important injury to the lumbar intervertebral disc? A 10-year matched cohort study. Spine J. 2016;16(3):273–280. doi:10.1016/j.spinee.2015.06.051.
Between 1996-1998, the authors recruited 75 subjects in a study of provocative discography (L3–S1) in asymptomatic or minimally symptomatic persons for LBP. From the same subject pools, the authors also recruited 75 matched subjects who would not have discography performed to act as control subjects. The authors report 16 lumbar surgeries in the discography group, as compared to 4 among the controls. Medical visits, work loss and prolonged episodes of back pain were more frequently encountered among patients who underwent discography. This study adds to the growing body of literature regarding the deleterious effect of discography on lumbar discs. The authors consider that the procedure should be understood as carrying a risk of accelerated disc degeneration at a minimum, and discussion and recognition of these risks should factor into the clinical ordering of the test, and the consent of the patient.
I wonder how they got that research through the IRB? Important to add this to the informed consent for this procedure.
The next three papers are related:
- Försth P, Ólafsson G, Carlsson T, et al. A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis. N Engl J Med. 2016;374(15):1413–1423. doi:10.1056/NEJMoa1513721.
They randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. The primary outcome was the score on the Oswestry Disability Index (ODI) 2 years after surgery. There was no significant difference between the groups in the mean score on the ODI at 2 years, and there were no significant differences between the groups in clinical outcomes at 5 years.
- Ghogawala Z, Dziura J, Butler WE, et al. Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis. N Engl J Med. 2016;374(15):1424–1434. doi:10.1056/NEJMoa1508788.
In this randomized, controlled trial, the authors assigned 66 patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone or laminectomy with posterolateral instrumented fusion. They found that lumbar laminectomy plus fusion was associated with a slightly greater but clinically meaningful improvement in physical health–related qualify of life than was laminectomy alone at 2, 3, and 4 years after surgery. The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group.
- Peul WC, Moojen WA. Fusion for Lumbar Spinal Stenosis – Safeguard or Superfluous Surgical Implant? N Engl J Med. 2016;374(15):1478–1479. doi:10.1056/NEJMe1600955.
This is the editorial that accompanies the previous two papers. This is a nice summary of the controversy: “Both trials show clearly that for most patients, stenosis surgery should be limited to decompression when no overt instability is present. Evidence from the trials by Försth et al. and Ghogawala et al. suggests that fusion for the treatment of stenosis is no longer the best practice and that its use should be restricted to patients who have proven spinal instability, as confirmed on flexion–extension radiographs; vertebral destruction caused by trauma, tumors, infections or spinal deformity..”
How do you define “instability”? Lots of leeway with the language.
- Laitio R, Hynninen M, Arola O, et al. Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest. Jama. 2016;315(11):1120. doi:10.1001/jama.2016.1933.
In animal studies, the neuroprotective properties of inhaled xenon have been established and are mediated through multiple putative molecular targets in the pathways involved in post resuscitation brain injury. Neuroprotection associated with xenon has been especially evident when combined with hypothermia. The authors investigated the effect of xenon on the extent of cerebral white matter brain damage as assessed by diffusion tensor magnetic resonance imaging (MRI) in comatose survivors from out-of-hospital cardiac arrest who had hypoxic-ischemic brain injury in a randomized 2-group single-blind phase 2 clinical trial at 2 multipurpose intensive care units (110 patients randomized). Patients were allocated to receive either therapeutic hypothermia treatment alone for 24 hours (control group) or inhaled xenon in combination with hypothermia for 24 hours. Inhaled xenon in combination with therapeutic hypothermia treatment preserved white matter better than hypothermia treatment alone in survivors of cardiac arrest. This was seen in higher fractional anisotropy values indicative of an attenuation of ongoing disruption of white matter microintegrity and lower radial diffusivity. However, while a benefit of xenon on white matter damage was observed, there were no significant difference in either neurological or cognitive outcomes between the 2 treatment groups. The study was underpowered due to the rarity of severe neurological impairment in long-term survivors after cardiac arrest; about 90% of patients who experience cardiac arrest and are alive at the 6-month follow-up have a good neurological outcome.
Selection bias, if you survive the initial insult, and are alive at 6 months you are pretty healthy and functional.
- Rigal J, Thelen T, Byrne F, et al. Prospective study using anterior approach did not show association between Modic 1 changes and low grade infection in lumbar spine. Eur Spine J. 2016;25(4):1000–1005. doi:10.1007/s00586-016-4396-5.
This study tried to determine if an association existed between lumbar disc degeneration and chronic infection of the intervertebral disc. 313 patients underwent a lumbar anterior video-assisted minimally invasive fusion or disc prosthesis in L4–L5 and/or L5–S1 via an anterior retroperitoneal approach. The patients MRI scans demonstrated in Pfirrmann’s classification grade IV or V disc degeneration. There were 303 Modic 1 changes, 58 Modic II changes and 24 absences of Modic change. All underwent intraoperative biopsy and were cultured for 4 weeks. Sterile cultures were obtained in 98%. They conclude that their results confirm the absence of any relationship between infection and disc degeneration.
Check mark in the AGAINST column for Modic changes being cause by low grade infection.
- Chavalarias D, Wallach JD, Li AHT, Ioannidis JPA. Evolution of Reporting P Values in the Biomedical Literature, 1990-2015. Jama. 2016;315(11):1141. doi:10.1001/jama.2016.1952.
The authors evaluated in large scale the P values reported in the abstracts and full text of biomedical research articles over the past 25 years and determine how frequently statistical information was presented in ways other than P values. They extracted data on P values reported in 12,821,790 MEDLINE abstracts and in 843,884 abstracts and full-text articles in PubMed Central (PMC) from 1990 to 2015. Reporting of P values in abstracts increased from 7.3% in 1990 to 15.6% in 2014. The distribution of reported P values in abstracts and in full text showed strong clustering at P values of .05 and of .001 or smaller. Among 99 manually extracted full-text articles with data, 55 reported P values, 4 presented confidence intervals for all reported effect sizes, none used Bayesian methods, 1 used false-discovery rates, 3 used sample size/power calculations, and 5 specified the primary outcome. Besides the substantial proportion of abstracts that report P values, a larger proportion of abstracts included qualitative statements about significance, mostly without any other quantitative information. They conclude that the transparency, accuracy, and information content of the biomedical literature would benefit from increased reporting of both effect sizes and measures of uncertainty or at least both effect size and P value in abstracts. Qualitative statements about significance in the absence of quantitative information are difficult to interpret should be avoided.
Qualitative statements without data backup are not helpful.
