Noninvasive electrical stimulation as an adjunct to fusion procedures: a systematic review and meta-analysis.

OBJECTIVE: Noninvasive electrical stimulation represents a distinct group of devices used to augment fusion rates. However, data regarding outcomes of noninvasive electrical stimulation have come from a small number of studies. The goal of this systematic review and meta-analysis was to determine outcomes of noninvasive electrical stimulation used as an adjunct to fusion procedures to improve rates of successful fusion. METHODS: PubMed, Embase, and the Cochrane Clinical Trials database were searched according to search strategy and PRISMA guidelines. Random-effects meta-analyses of fusion rates with the three main modalities of noninvasive electrical stimulation, capacitively coupled stimulation (CCS), pulsed electromagnetic fields (PEMFs), and combined magnetic fields (CMFs), were conducted using R version 4.1.0 (The R Foundation for Statistical Computing). Both retrospective studies and clinical trials were included. Animal studies were excluded. Risk-of-bias analysis was performed with the Risk of Bias 2 (RoB 2) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tools. RESULTS: Searches of PubMed, Embase, and the Cochrane Clinical Trials database identified 8 articles with 1216 participants meeting criteria from 213 initial results. There was a high overall risk of bias identified for the majority of randomized studies. No meta-analysis could be performed for CCS as only 1 study was identified. Meta-analysis of 6 studies of fusion rates in PEMF did not find any difference between treatment and control groups (OR 1.89, 95% CI 0.36-9.80, p = 0.449). Meta-analysis of 2 studies of CMF found no difference in fusion rates between control and treatment groups (OR 0.90, 95% CI 0.07-11.93, p = 0.939). Subgroup analysis of PEMF was limited given the small number of studies and patients, although significantly increased fusion rates were seen in some subgroups. CONCLUSIONS: This meta-analysis of clinical outcomes and fusion rates in noninvasive electrical stimulation compared to no stimulation did not identify any increases in fusion rates for any modality. A high degree of heterogeneity between studies was noted. Although subgroup analysis identified significant differences in fusion rates in certain groups, these findings were based on a small number of studies and further research is needed. This analysis does not support routine use of these devices to augment fusion rates, although the data are limited by a high risk of bias and a small number of available studies.

Diminishing returns with successive device passes in mechanical thrombectomy for stroke.

BACKGROUND: Multiple device passes are associated with complications and poor functional outcomes following mechanical thrombectomy (MT) for emergent large vessel occlusion (ELVO). OBJECTIVE: To characterize the relationship between number of device passes, complications, angiographic outcomes, and clinical outcomes in MT for ELVO. METHODS: This is a single-center, retrospective cohort study. Individual device passes for MT were evaluated for any change in Thrombolysis in Cerebral Infarction (TICI) score, successful revascularization (TICI 2b or 3), and complications. Outcomes were compared among groups requiring multiple passes with various cut-off points. Risk factors for unfavorable clinical outcome [90 day modified Rankin Scale > 2] were assessed using multivariate analysis. RESULTS: Successful revascularization was achieved in 75% of 163 patients and 36% required only one device pass. After the second pass, the likelihood of angiographic improvement significantly decreased (p < 0.001). Using multiple cut-off points, higher post-procedural NIHSS scores, mortality rates, and unfavorable 90-day outcomes were associated with a greater number of passes. Multivariate analysis revealed ICA thrombus (comparison: M2, OR: 25, 95% CI 2-275, p = 0.01) and failed revascularization (OR: 68, 95% CI 3.12-1489, p = 0.01) as the only significant predictors of unfavorable clinical outcome. Nonetheless, the likelihood of favorable clinical outcome was higher in patients with an ICA occlusion who were revascularized in < 2 vs. ≥ 2 (44 vs 4%, p = 0.01) or < 3 vs. ≥ 3 (32 vs. 0%, p = 0.02) passes. CONCLUSION: The likelihood of angiographic improvement in patients with ELVO significantly decreases after the second pass. A greater number of passes is associated with worsened clinical outcomes.

Retrograde ejaculation following anterior lumbar surgery: a systematic review and pooled analysis.

OBJECTIVE: The present systematic review and pooled analysis aims to assess the incidence and risk factors for the development of retrograde ejaculation (RE) following first-time open anterior lumbar surgery. METHODS: A systematic MEDLINE review via PubMed was performed, identifying 130 clinical papers relating to the topic. Eighteen publications were selected according to predetermined inclusion and exclusion criteria and were used to determine the incidence of RE. Only the publications that provided data on surgical risk factors present specifically in the men in the study were included in the analysis of risk factors. RESULTS: Of the 2503 men included, there were 57 reported events of RE (2.3%). Of the cases for which long-term data were provided, 45.8% had resolved by final follow-up. There was a statistically significant increased risk associated with a transperitoneal as opposed to a retroperitoneal approach (8.6% vs 3.2%), as well as with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) as opposed to ALIF with bone graft or arthroplasty in controls (5.0% vs 1.8%). However, when excluding from analysis the patients operated on prior to the FDA's 2008 warning that commented on the drug's neuroinflammatory properties, there was no significant difference in rates of RE in patients receiving rhBMP-2 versus the control group (2.4% vs 2.5%). There was no significant difference in risk based on single- versus multilevel procedure or on ALIF versus arthroplasty. CONCLUSIONS: In a pooled analysis of currently published data on men undergoing first-time open anterior lumbar surgery, this study found an overall incidence of RE of 2.3%. Nearly half of these patients recovered, reporting resolution of symptoms anywhere between 3 months and 48 months. Analysis of risk factors was limited by a paucity of published literature segregating data by sex. However, there was an increased risk associated with rhBMP-2 only when including data collected prior to the FDA warning on its detrimental properties. The authors therefore posit that the risk of RE is probably overestimated in the literature, given that the vast majority of the data available were collected prior to this warning and given the subsequent implementation of precautions when handling rhBMP-2.

The History of Anterior and Lateral Approaches to the Lumbar Spine.

Anterior and lateral approaches to the lumbar spine are commonly used today for a variety of indications. These approaches can ultimately be traced back to early attempts to treat Pott's disease. Evidence of Mycobacterium tuberculosis infection of the spine dates as far back as 2400 BCE, with ancient Egyptian mummies exhibiting lesions consistent with Pott's disease. For many centuries, Pott's disease was treated conservatively, and surgery came to be used when conservative therapy was ineffective, as medical therapy had yet to become available. In 1779, Percivall Pott recommended that peripheral paraspinal tuberculous abscesses be drained after noticing that patients' lower limb function improved after the formation of spontaneous draining sinuses. Building on Pott's ideas, Ménard described the first lateral approach to the spine via a costotransversectomy approximately 1 century after Pott's theory. Most importantly, the surge in understanding anatomy with respect to developing safe corridors to the deeper structures of the human body brought together advances in technology, instrumentation, and visualization. Surgeons were thus emboldened to explore more complex anterior approaches to the spine. In 1906, Müller reported the first successful anterior approach to the spine in a patient with Pott's disease. Over the next several decades, the efforts of surgeons such as Ito, Capener, Burns, and Mercer would lead to the development of the anterior lumbar interbody fusion. The costotransversectomy later evolved into the lateral rhachotomy and lateral extracavitary approach, which along with advances in the anterior lumbar interbody fusion paved the way for the oblique lumbar interbody fusion and lateral lumbar interbody fusion.

Safety and efficacy of brain injury guidelines at a Level III trauma center.

BACKGROUND: Patients with mild to moderate traumatic brain injury (TBI) are often primarily managed by emergency medicine and trauma/acute care physicians. The Brain Injury Guidelines (BIG) were developed at an American College of Surgeons-accredited Level 1 trauma center to triage mild to moderate TBI patients and help identify patients who warrant neurosurgical consultation. The BIG have not been validated at a Level III trauma center. We hypothesized that BIG criteria can be safely adapted to an American College of Surgeons-accredited Level III trauma center to guide transfers to a higher echelon of care. METHODS: We reviewed the trauma registry at a Level III trauma center to identify TBI patients who presented with an Abbreviated Injury Severity-Head score greater than zero. Demographic data, injury details, and clinical outcomes were abstracted with primary outcome measures of worsening on second computed tomography of the head, neurosurgical intervention, transfer to a Level I trauma center, and in-hospital mortality. Patients were classified using the BIG criteria. After validating the BIG in our cohort, we reclassified patients using updated BIG criteria. Updated criteria included mechanism of injury, reclassification of anticoagulation or antiplatelet use, and replacement of the neurologic examination component with stratification by admission Glasgow Coma Scale (GCS) score. RESULTS: From July 2013 to June 2016, 332 TBI patients were identified: 115 BIG-1, 25 BIG-2, and 192 BIG-3. Patients requiring neurosurgical intervention (n = 30) or who died (n = 29) were BIG-3 with one exception. Patients with GCS score of less than 12 had worse outcomes than those with a GCS score of 12 or greater, regardless of BIG classification. Anticoagulant or antiplatelet use was not associated with worsened outcomes in patients not meeting other BIG-3 criteria. The updated BIG resulted in more patients in BIG-1 (n = 109) and BIG-2 (n = 100) without negatively affecting outcomes. CONCLUSION: The BIG can be applied in the Level III trauma center setting. Updated BIG criteria can aid triage of mild to moderate TBI patients to a Level I trauma center and may reduce secondary overtriage. LEVEL OF EVIDENCE: Care management, level IV.

Factors associated with pulmonary embolism within 72 hours of admission after trauma: a multicenter study.

BACKGROUND: Recent studies using thromboelastography indicate that patients are at risk for hypercoagulability early after injury. Pulmonary embolism (PE) is also well known to cause significant morbidity and mortality after injury and can occur within 72 hours of admission (early PE). Despite this risk, prophylactic anticoagulation is often delayed in patients with certain injuries due to concerns about bleeding. STUDY DESIGN: This was a retrospective study of injured patients with a PE from 2007 to 2013 at 3 level I trauma centers. Data collected included patient demographics, injury patterns, length of stay, timing of prophylaxis for deep vein thrombosis (DVT), and diagnosis of PE. Patients with early PE (≤ 3 days) were compared with those with late PE (>3 days) using bivariate and multivariable analysis. RESULTS: A total of 54,964 patients were admitted to the 3 centers during the study period, and 144 (0.26%) were diagnosed with a PE. Eleven were excluded from the study due to a lack of critical data, leaving 133 patients (43% early PE). Factors associated with early PE included long bone fractures in the lower extremity and an Abbreviated Injury Score (AIS) Extremity ≥ 3. Higher Injury Severity Score, severe chest and head trauma (AIS ≥ 3), and not receiving DVT prophylaxis within 48 hours of hospital admission were not associated with early PE. CONCLUSIONS: Early PE is a significant clinical entity occurring in nearly half the patients who suffered a PE. Early PE is associated with long bone fractures and severe extremity trauma, but not severe thoracic injury. Timing of prophylactic anticoagulation had no impact on early PE. If further studies confirm this incidence of unsuspected early PE, all admitted trauma patients should be assessed for a hypercoagulable state after injury.

Pph13 and orthodenticle define a dual regulatory pathway for photoreceptor cell morphogenesis and function.

The function and integrity of photoreceptor cells are dependent upon the creation and maintenance of specialized apical structures: membrane discs/outer segments in vertebrates and rhabdomeres in insects. We performed a molecular and morphological comparison of Drosophila Pph13 and orthodenticle (otd) mutants to investigate the transcriptional network controlling the late stages of rhabdomeric photoreceptor cell development and function. Although Otd and Pph13 have been implicated in rhabdomere morphogenesis, we demonstrate that it is necessary to remove both factors to completely eliminate rhabdomere formation. Rhabdomere absence is not the result of degeneration or a failure of initiation, but rather the inability of the apical membrane to transform and elaborate into a rhabdomere. Transcriptional profiling revealed that Pph13 plays an integral role in promoting rhabdomeric photoreceptor cell function. Pph13 regulates Rh2 and Rh6, and other phototransduction genes, demonstrating that Pph13 and Otd control a distinct subset of Rhodopsin-encoding genes in adult visual systems. Bioinformatic, DNA binding and transcriptional reporter assays showed that Pph13 can bind and activate transcription via a perfect Pax6 homeodomain palindromic binding site and the Rhodopsin core sequence I (RCSI) found upstream of Drosophila Rhodopsin genes. In vivo studies indicate that Pph13 is necessary and sufficient to mediate the expression of a multimerized RCSI reporter, a marker of photoreceptor cell specificity previously suggested to be regulated by Pax6. Our studies define a key transcriptional regulatory pathway that is necessary for late Drosophila photoreceptor development and will serve as a basis for better understanding rhabdomeric photoreceptor cell development and function.