Anterior vertebral body tethering shows clinically comparable shoulder balance outcomes to posterior spinal fusion.

PURPOSE: Posterior spinal fusion (PSF) is the current gold standard in surgical treatment for adolescent idiopathic scoliosis. Vertebral body tethering (VBT) is a fusionless alternative. Shoulder balance is an important metric for outcomes and patient satisfaction. Here we compare shoulder balance outcomes between PSF and VBT. METHODS: In this retrospective review, the pre-operative and post-operative absolute radiographic shoulder height (|RSH|) of 45 PSF patients were compared to 46 VBT patients. Mean values were compared and then collapsed into discrete groups (|RSH| GROUP) and compared. Patients were propensity score matched. Regression models based on pretest-posttest designs were used to compare procedure type on post-operative outcomes. RESULTS: Pre-operatively there were no differences in |RSH| between PSF and VBT, however, at latest post-operative follow-up PSF maintained a larger |RSH| imbalance compared to VBT (0.91 cm vs 0.63 cm, p = 0.021). In an ANCOVA regression, PSF was associated with a larger |RSH| imbalance compared to VBT, F(1, 88) = 5.76, p = 0.019. An ordinal logistic regression found that the odds ratio of being in a worse |RSH| GROUP for PSF vs VBT is 2.788 (95% CI = 1.099 to 7.075), a statistically significant effect χ2(1) = 4.658, p = 0.031. Results were similar in subgroup analyses of Lenke 1 and Lenke 2 patients, though to less statistical significance. CONCLUSION: While PSF was found to be associated with worse |RSH| outcomes, the actual numbers (2-3 mm) are unlikely to be clinically meaningful. Thus, in this analysis, VBT can be said to show comparable shoulder balance outcomes to PSF.

Anterior Vertebral Body Tethering for Scoliosis Patients With and Without Skeletal Growth Remaining: A Retrospective Review With Minimum 2-Year Follow-Up.

BACKGROUND: Anterior vertebral body tethering (AVBT) has been approved for skeletally immature (IM) adolescent idiopathic scoliosis patients, but the role of AVBT in patients with minimal remaining skeletal growth is controversial. The purpose of this study was to compare minimum 2-year (YR2) outcomes in skeletally IM patients vs those with minimal remaining skeletal growth. METHODS: Patients with single thoracic AVBT were grouped by their preoperative (PR) skeletal maturity: IM (n = 16, Risser 0-2) vs mature (M, n = 19, Risser 3-5). Outcomes were assessed at PR, first erect (FE), and YR2. Median (range) was compared with nonparametric tests (P < 0.05). RESULTS: The PR age was 12.5 (9-16) vs 15 (12-18) years with major Cobb 51° (36°-69°) and 49° (40°-69°) for IM and M, respectively. At FE, there was no difference in correction; however, at YR2, the IM group yielded a lower residual curve (15° [-16° to 38°] vs 29° [12°-42°], P = 0.008). Thoracolumbar/lumbar curves were corrected without group differences. Clinically successful correction (<35°) (15 [94%] vs 15 [79%]) and suspected cord breakages (2 [13%] vs 2 [12%]) were similar at YR2. Two overcorrections occurred, both in IM patients. Scoliosis Research Society-22 outcomes at final follow-up were similar between groups. No revision reoperations or conversions to spinal fusion were needed. CONCLUSIONS: Skeletally IM patients benefit from greater growth-modulated curve correction than M patients, however, at the increased risk of overcorrection. M patients maintained clinically significant correction at latest follow-up. Longer-term follow-up is required to determine durability of outcomes for patients undergoing AVBT who have minimal remaining growth at the time of index surgery. CLINICAL RELEVANCE: This study is relevant to spine surgeons, spine physiotherapists, and patients with idiopathic scoliosis. It offers evidence of clinical correction of scoliosis in mature patients.

Vertebral Body Tethering in 49 Adolescent Patients after Peak Height Velocity for the Treatment of Idiopathic Scoliosis: 2-5 Year Follow-Up.

Vertebral Body Tethering (VBT) is a non-fusion surgical treatment for Adolescent Idiopathic Scoliosis (AIS) that elicits correction via growth modulation in skeletally immature patients. VBT after peak height velocity is controversial and is the subject of this study. A retrospective review of Risser 3−5 AIS patients treated with VBT, and min. 2-year FU was performed. Pre to post-op changes in clinical outcomes were compared using Student's t-test or the Mann-Whitney test. A total of 49 patients met criteria, age 15.0 ± 1.9 years, FU 32.5 ± 9.1 months. For thoracic (T) major curvatures, T curvature improved from 51.1 ± 6.9° to 27.2° ± 8.1° (p < 0.01) and TL from 37.2° ± 10.7° to 19.2° ± 6.8° (p < 0.01). For thoracolumbar (TL) major curvatures, T improved from 37.2° ± 10.7° to 18.8° ± 9.4° (p < 0.01) and TL from 49.0° ± 6.4° to 20.1° ± 8.5° (p < 0.01). Major curve inclinometer measurements and SRS-22 domains, except activity, improved significantly (p ≤ 0.05). At the latest FU, one (2%) patient required fusion of the T curve and revision of the TL tether due to curve progression in the previously uninstrumented T curve and tether breakage (TB) in the TL. Twenty (41%) patients experienced TB. VBT in AIS patients with limited remaining skeletal growth resulted in satisfactory clinical outcomes at the latest FU.

Genipin-crosslinked fibrin seeded with oxidized alginate microbeads as a novel composite biomaterial strategy for intervertebral disc cell therapy.

Discectomy procedures alleviate disability caused by intervertebral disc (IVD) herniation, but do not repair herniation-induced annulus fibrosus (AF) defects. Cell therapy shows promise for IVD repair, yet cell delivery biomaterials capable of sealing AF defects and restoring biomechanical function have poor biological performance. To balance the biomechanical and biological demands of IVD cell delivery biomaterials, we engineered an injectable composite biomaterial using cell-laden, degradable oxidized alginate (OxAlg) microbeads (MBs) to deliver AF cells within high-modulus genipin-crosslinked fibrin (FibGen) hydrogels (FibGen + MB composites). Conceptually, the high-modulus FibGen would immediately stabilize injured IVDs, while OxAlg MBs would protect and release cells required for long-term healing. We first showed that AF cells microencapsulated in OxAlg MBs maintained high viability and, upon release, displayed phenotypic AF cell morphology and gene expression. Next, we created cell-laden FibGen + MB composites and demonstrated that OxAlg MBs functionalized with RGD peptides (MB-RGD) minimized AF cell apoptosis and retained phenotypic gene expression. Further, we showed that cell-laden FibGen + MB composites are biomechanically stable and promote extracellular matrix (ECM) synthesis in long-term in vitro culture. Lastly, we evaluated cell-laden FibGen + MB-RGD composites in a long-term bovine caudal IVD organ culture bioreactor and found that composites had low herniation risk, provided superior biomechanical and biological repair to discectomy controls, and retained anabolic cells within the IVD injury space. This novel injectable composite hydrogel strategy shows promise as an IVD cell delivery sealant with potentially broad applications for its capacity to balance biomechanical and biological performance.

Post-operative tranexamic acid decreases chest tube drainage following vertebral body tethering surgery for scoliosis correction.

PURPOSE: Anterior vertebral body tethering (VBT) is a non-fusion surgical treatment for Adolescent Idiopathic Scoliosis requiring chest tube(s) (CT). We sought to assess the efficacy of post-op intravenous tranexamic acid (IV TXA) in reducing CT drainage and retention. METHODS: 35 VBT patients received 24 h of post-op IV TXA (2 mg/kg/h) were compared to 49 who did not. Group comparisons were performed using Wilcoxon rank-sum and chi-squared tests. Multivariate linear regression analysis was used to assess the relationships between TXA and both CT drainage and retention time. RESULTS: There were no group differences at baseline (Table). CTs placed for thoracic (T) and thoracolumbar (TL) curves were assessed separately. For TH CT, there was less total CT drainage in the TXA group (TXA 569.4 ± 337.4 mL vs. Non-TXA 782.5 ± 338.9 mL; p = 0.003) and shorter CT retention time (TXA 3.0 ± 1.3 vs. Non-TXA 3.9 ± 1.4 days; p = 0.003). For TL CT, there was less total CT drainage in the TXA group (TXA 206.8 ± 152.2 mL vs. Non-TXA 395.7 ± 196.1 mL; p = 0.003) and shorter CT retention time (TXA 1.7 ± 1.3 vs. Non-TXA 2.7 ± 1.0 days; p = 0.001). Following multivariate analysis, use of TXA was the only significant predictor of both drainage in T and TL CTs (p = 0.012 and p = 0.002, respectively) as well as T and TL CT retention time (p = 0.008 and p = 0.009, respectively). There were no differences in LOS (p = 0.863) or ICU stay (p = 0.290). CONCLUSION: IV TXA results in a significant decrease in CT drainage and retention time. CT retention is decreased by 1 day for those that receive TXA. LEVEL OF EVIDENCE: III.

Early operative morbidity in 184 cases of anterior vertebral body tethering.

Fusion is the current standard of care for AIS. Anterior vertebral body tethering (AVBT) is a motion-sparing alternative gaining interest. As a novel procedure, there is a paucity of literature on safety. Here, we report 90-day complication rates in 184 patients who underwent AVBT by a single surgeon. Patients were retrospectively reviewed. Approaches included 71 thoracic, 45 thoracolumbar, 68 double. Major complications were those requiring readmittance or reoperation, prolonged use of invasive materials such as chest tubes, or resulted in spinal cord or nerve root injury. Minor complications resolved without invasive intervention. Mean operative time and blood loss were 186.5 ± 60.3 min and 167.2 ± 105.0 ml, respectively. No patient required allogenic blood transfusion. 6 patients experienced major (3.3%), and 6 had minor complications (3.3%). Major complications included 3 chylothoracies, 2 hemothoracies, and 1 lumbar radiculopathy secondary to screw placement requiring re-operation. Minor complications included 1 patient with respiratory distress requiring supplementary oxygen, 1 superficial wound infection, 2 cases of prolonged nausea, and 1 Raynaud phenomenon. In 184 patients who underwent AVBT for AIS, major and minor complication rates were both 3.3%.

Genomic architecture of Shh-dependent cochlear morphogenesis.

The mammalian cochlea develops from a ventral outgrowth of the otic vesicle in response to Shh signaling. Mouse embryos lacking Shh or its essential signal transduction components display cochlear agenesis; however, a detailed understanding of the transcriptional network mediating this process is unclear. Here, we describe an integrated genomic approach to identify Shh-dependent genes and associated regulatory sequences that promote cochlear duct morphogenesis. A comparative transcriptome analysis of otic vesicles from mouse mutants exhibiting loss (Smoecko ) and gain (Shh-P1) of Shh signaling reveal a set of Shh-responsive genes partitioned into four expression categories in the ventral half of the otic vesicle. This target gene classification scheme provides novel insight into several unanticipated roles for Shh, including priming the cochlear epithelium for subsequent sensory development. We also mapped regions of open chromatin in the inner ear by ATAC-seq that, in combination with Gli2 ChIP-seq, identified inner ear enhancers in the vicinity of Shh-responsive genes. These datasets are useful entry points for deciphering Shh-dependent regulatory mechanisms involved in cochlear duct morphogenesis and establishment of its constituent cell types.

More unaffected first-degree relatives of essential tremor cases have mild cognitive deficits than age-matched controls.

BACKGROUND: In numerous case-control studies, essential tremor (ET) has been associated with cognitive impairment. ET is often familial. However, cognitive impairment has not been studied in family members of ET cases. Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease; as such, they may be present before disease onset. We administered a global cognitive screen to first-degree relatives of ET cases (FD-ET) and age-matched controls (Co). METHODS: We administered the Montreal Cognitive Assessment (MoCA) to 156 FD-ET and 73 Co, none of whom were diagnosed with ET or reported tremor. MoCA <26 was considered suggestive of cognitive impairment. RESULTS: FD-ET and Co were similar with respect to age (60.1 ±â€¯8.3 vs. 60.9 ±â€¯7.4 years) and numerous demographic factors. FD-ET and Co also had similar MoCA scores; however, 34 of 156 (21.8%) FD-ET had a MoCA score <26 vs only 5 (6.9%) of 73 Co (p = 0.004). In a univariate logistic regression model, FD-ET were 3.79 times more likely to have a low (<26) MoCA than were Co (odds ratio = 3.79, p = 0.008). In a multivariate logistic regression model, adjusting for age and other covariates, FD-ET were 4.83 times more likely to have a low MoCA than were Co (odds ratio = 4.83, p = 0.003). CONCLUSION: More FD-ET had low MoCA scores when compared with Co. These data provide additional support for the scientific notions that (1) cognitive difficulties are a disease-associated feature of ET and (2) there may be a pre-tremor phase of illness in ET.

Transient, Isolated Head Tremor in "Unaffected" Individuals: Is Essential Tremor an Even More Prevalent Disease Than We Suppose?

Background: Mild and transient head tremor may sometimes be observed in otherwise tremor-free relatives of essential tremor (ET) cases, although its prevalence is unclear. A diagnostic question is whether this transient, isolated head tremor, often observed as no more than a wobble, is an early manifestation of ET or whether it is a normal finding. A direct comparison with controls is needed. Methods: Two hundred and forty-one first-degree relatives of ET cases (FD-ET) and 77 spousal controls (Co) were enrolled in a study of ET. Each underwent a detailed evaluation that included a tremor history and videotaped neurological examination. None of the enrollees reported tremor, had a prior diagnosis of ET, or had significant tremor on screening spirals. All videotaped examinations were initially reviewed by a movement disorder neurologist blinded to subject type, and among those with head tremor on examination, co-reviewed by two additional movement disorders neurologists. Results: Twenty-six (10.8, 95% Confidence interval [CI] = 7.5-15.3%) of 241 FD-ET vs. 2 (2.6, 95% CI = 0.7-9.0%) of 77 Co had isolated, transient head tremor (odds ratio = 4.54, 95% CI = 1.05-19.57, p = 0.04). No enrollee had significant upper extremity tremor and none met inclusion criteria for ET based on the presence of upper extremity tremor. With one exception, head tremor occurred during or after phonation. It was always transient (generally a single back and forth wobble) and rare (observed briefly on one or two occasions during the videotaped examination) and had a faster frequency, lower amplitude and a different quality than voluntary head shaking. Conclusion: The basis for the observed isolated head tremor is unknown, but it could be an early feature of ET in ET families.Indeed, one-in-ten otherwise unaffected first-degree relatives of ET cases exhibited such tremor. To a far lesser extent it was also observed in "unaffected" controls. In both, it is likely a sign of early, emerging, undiagnosed ET, although follow-up studies are needed to confirm this. If it were ET, it would indicate that the prevalence of ET may be considerably higher than previously suspected.

Caffeine Consumption in First-Degree Relatives of Essential Tremor Cases: Evidence of Dietary Modification Before Disease Onset.

BACKGROUND: Caffeine can exacerbate tremor. Reducing caffeine intake or switching to decaffeinated beverages can lessen tremor. Unaffected relatives of essential tremor (ET) cases often have mild, subclinical tremor. One question is whether the coffee and tea consumption pattern in these individuals differs from that of controls (Co). METHODS: We ascertained the patterns of coffee and tea intake using a structured questionnaire, and compared the use in unaffected first-degree relatives of ET cases (FD-ET) to the use in age-matched Co. Three measures of relative caffeinated coffee + tea to decaffeinated coffee + tea were constructed. Caffeine index 1 = (cups of caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed on the day of evaluation. Caffeine index 2 = (cups of caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed in a typical month. The percentage of coffee and tea that was caffeinated in a typical month was also calculated. RESULTS: There were 263 individuals (190 FD-ET, 73 Co). Caffeine index 1 in FD-ET was less than 1-half that of Co (p = 0.001). Caffeine index 2 was similarly lower in FD-ET than Co (p = 0.027). The percentage of coffee and tea that was caffeinated in a typical month was also significantly lower in FD-ET than Co (p = 0.018). CONCLUSION: The balance of caffeinated to decaffeinated beverages is different in FD-ET than Co. These data raise several intriguing questions. Among these is whether relatives of ET cases modify their caffeine consumption before disease onset.

Unaffected first-degree relatives of essential tremor cases have more imbalance than age-matched control subjects.

BACKGROUND: Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease (e.g., unaffected family members). Endophenotypes are useful; they may clarify diagnosis in genetic studies and foster the development of animal models. In recent years, problems with balance and mild gait ataxia have been associated with essential tremor (ET). We compared gait and balance of first-degree relatives of ET cases (FD-ET) to that of age-matched controls (Co). METHODS: One-hundred-ninety FD-ET and 68 Co, none of whom reported tremor or were diagnosed with ET, underwent a standardized assessment of gait and balance. RESULTS: FD-ET reported more near-falls in the past year (p = 0.015) and lower balance confidence according to the Activities of Balance Confidence (ABC-6) Scale (p = 0.03). The specific ABC-6 items for which FD-ET reported lower balance confidence than Co were being bumped into by people while walking (p = 0.006) and walking outside on icy sidewalks (p = 0.007). On videotaped neurological examination, FD-ET were able to stand in the tandem position for fewer seconds than were Co (p = 0.048). The differences between FD-ET and Co, although statistically significant, were clinically mild. CONCLUSION: FD-ET reported more near-falls in the past year and a reduction in balance confidence; additionally, ability to maintain tandem stance was impaired compared to Co. These data suggest a more pervasive abnormality of cerebellar dysfunction than previously conceived, extending beyond ET cases themselves and manifesting in mild form in their unaffected family members.

Comparative Burden of Subclinical Tremor in a Cohort of Normal Individuals Stratified by Familial Risk for Essential Tremor.

BACKGROUND: The burden of mild (i.e., subclinical) tremor within essential tremor (ET) families is not fully understood. We assessed the burden of mild tremor in a cohort of 287 adults, none of whom reported tremor or were diagnosed with ET. METHODS: We recruited adults in 2 groups based on the familial risk for ET: 244 high-risk individuals (i.e., reporting one or more first-degree relative with ET) and 43 low-risk individuals (i.e., reporting no relatives with ET). Tremor was objectively assessed on 4 hand-drawn spirals (total spiral score = 0-12). Mild tremor was defined using 3 different cut points. RESULTS: The prevalence rates of mild tremor among high-risk individuals ranged from 41.4 to 98.4% and were highly dependent on the cut point. Above a certain threshold (i.e., a total spiral score ≥5), 1-in-5 (i.e., 19.7%) high-risk individuals exhibited mild tremor, whereas no low-risk individuals did. High-risk individuals were 3.09-4.50 times more likely than low-risk individuals to exhibit mild tremor. CONCLUSION: The burden of ET extends beyond the boundaries of the clinically defined disease, and partially expressed forms of ET are abundant in ET families. This fact greatly complicates gene-finding studies and epidemiological studies whose goal is to detect disease-linked associations.

Early Head Tremor in Essential Tremor: A Case Series and Commentary.

BACKGROUND: Classically, the onset of head tremor in essential tremor (ET) patients follows that of hand tremor, such that there is a somatotopic spread of involved areas. Here we present a series of seven self-reportedly "unaffected" relatives of ET cases. These seven were clinically asymptomatic and had normal levels of arm tremor on examination, yet each evidenced a transient head wobble on examination. We estimate the prevalence of this phenotype within the two studies from which cases were ascertained. METHODS: ET cases and their self-reportedly affected and unaffected relatives, enrolled in two family studies, underwent a medical history and videotaped neurological examination. RESULTS: In seven self-reportedly "unaffected" relatives, a transient and subtle head wobble was seen, always during sustained phonation, speech, or reading aloud. Total tremor score (a measure of arm tremor) ranged from 5 to 12 (i.e., mild tremor within the range of normal). The prevalence of this phenotype of early head tremor was 3.7% in one study and 23.1% in the other. DISCUSSION: We present a series of seven individuals who had early head tremor in an evolving transition state from normal to ET. These cases raise a number of broad clinical, phenotypic, and pathophysiological issues about ET.

Agricultural safety training: California style.

In response to 1990 regulations in California, agricultural industry leaders formed a coalition with academic institutions and farm organizations to ensure they were compliant with new standards for worker safety in agricultural work settings. Out of this coalition emerged a not-for-profit organization, AgSafe. This was followed by a formal training program, the California Agricultural Safety Certificate Program. Now with more than 10 years' experience, this program has evolved into a highly successful initiative that garners industry support throughout the state. Courses can be taken at one annual event or at intervals, including regionalized offerings. The AgSafe program and other training workshops have helped agricultural producers/employers more rapidly and effectively adopt best management practices in an increasingly more complicated regulatory environment. In the process it has enhanced a culture of safety and introduced valuable strategies that increase productivity while improving safety and health outcomes for workers. To date, nearly 550 individuals have secured certificates of completion that reflect at least 15 hours of formal coursework. English- and Spanish-language training is offered in a manner that is responsive to the learning styles of a multicultural workforce. California's approach for safety training of agricultural workers can serve as a model for enhancing respect and cooperation among employers, workers, and safety professionals.

Racial differences in mortality among men hospitalized in military hospitals.

A comparative study was conducted on patients in military hospitals in response to recent studies at veterans hospitals showing the possibility that access to an equal-access health care system may reduce or reverse racial differences in mortality outcomes. Using a cohort study of 14,122 military retirees admitted to military hospitals with any of six common medical diagnoses between October 2000 and September 2004, we evaluated differences in patient and hospital characteristics and evaluated race-specific hospital mortality. Despite long-term equal access to comprehensive medical care, there were significant racial differences in patient- and hospital-level risk factors among male military retirees hospitalized with common medical diagnoses. In unadjusted analyses, risk of hospital mortality was significantly lower in African Americans and other non-Caucasians when compared to Caucasians, but differences disappeared after adjustment for all risk factors.

Rest break interventions in stoop labor tasks.

Hand cultivation and harvest of agricultural products constitute strenuous physical tasks. Working with labor-management ergonomics committees in agricultural settings, the UC Agricultural Ergonomics Research Center (AERC) tested an experimental rest and recovery protocol for its impact on symptoms and productivity during two types of work tasks. The experimental condition consisted of adding a 5 min rest break to every working hour in which there was no other scheduled break (e.g., lunchtime). This resulted in an additional 20 min of rest per workday. We tested the intervention in two trials: Trial one compared workers (n=66) randomly assigned to an experimental or a control group during the harvest of commercial strawberries. Trial two utilized a cross-over design (n=16 pairs of workers) to compare experimental and control conditions while workers inserted bud grafts into young 18'' high citrus trees. For both trials, workers under the experimental condition reported significantly less severe symptoms than workers under control conditions. The order in which the intervention was given, however, appeared to result in variations in productivity. We conclude that the introduction of frequent, brief rest breaks may improve symptoms for workers engaged in strenuous work tasks.

Priority risk factors for back injury in agricultural field work: vineyard ergonomics.

With support of a NIOSH Community Partners grant, the authors reviewed data from three cooperating vineyard companies in Napa and Sonoma Counties, finding both high rates of evidence of musculoskeletal disorders (MSDs) and identifying priority MSD hazards for intervention. Data from OSHA 200 injury report logs identified 29 reported MSDs and 435 lost workdays in a working population of 194 in a 30-month period. The majority of these (20) involved backstrain. High risk job tasks were identified, including: employer-identified tasks, analysis of injury reports, and ergonomics risk factor checklist survey of task work. Triangulating across these three data groups resulted in identification of high priority tasks, including: hand harvest work, hand pruning, and weeding using shovels. Priority risk factors for back injury in these jobs were: repetitive lifting of heavy loads, repetitive exertion of force by the trunk and upper extremities, and repetitive or sustained awkward postures of the trunk (including full stoop and twisting with loads).