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BACKGROUND Vascularized bone grafts (VBGs) are associated with improved union and fewer instrumentation complications in the mobile spine. It is not known if VBGs are similarly efficacious after sacrectomy. METHODS We conducted a retrospective chart review of all patients who underwent total sacrectomy and immediate reconstruction with VBG between 2005 and 2019. Patient and surgical characteristics in addition to union and functional outcomes were analyzed. RESULTS We identified 10 patients (6 women and 4 men) with a mean age of 42 years (range, 12-71 years). All patients received iliolumbar instrumentation as well as a free fibula flap as a VBG. There were no complications at the fibula flap donor site or specifically related to the VBG. Bony union was achieved in 7 (88%) of 8 patients with an average union time of 6.3 months (range, 2-10 months). Surgical complications occurred in 5 patients, 4 patients required reoperation for wound dehiscence, and 1 patient required conversion to a 4-rod construct and bone grafting for instrumentation loosening and partial nonunion. Instrumentation failure developed in 1 patient, but no surgical intervention was required. One patient was able to walk independently without any limitation, 5 patients required a walker, 2 were wheelchair-bound except for short (

Background Type 1 internal hemipelvectomies and total sacrectomies cause significant biomechanical instability, demanding pelvic ring reconstruction for ambulation and torso support. Previously described methods include autografts, allografts, and implants, commonly with poor long-term outcomes. The authors hypothesized that the free fibula flap for spinopelvic reconstruction is safe and effective, and associated with a high bony union rate and superior functional outcomes. Methods The authors performed a retrospective review of all patients who underwent free fibula flap surgery after internal hemipelvectomy or total sacrectomy at M. D. Anderson Cancer Center from 2003 to 2018. The primary outcome was radiographic evidence of bony union. Secondary outcomes included surgical-site occurrence and lower extremity function. Univariate and multivariate logistic regression analyses were performed. Results Forty-seven patients were included (internal hemipelvectomy, n = 38; total sacrectomy, n = 9). The mean follow-up was 3.3 years and the most common abnormality was chondrosarcoma (30.4 percent). The nonunion rate was 9.7 percent and the surgical-site occurrence rate was 34 percent; there were no flap losses. Greater age was significantly associated with nonunion (OR, 1.1; 95 percent CI, 1 to 1.2; p = 0.003), whereas obesity was the only independent predictor of surgical-site occurrence (OR, 9.2; 95 percent CI, 1.2 to 71.3; p = 0.03). Functional metrics approached those of adult norms by 3 years postoperatively. Compared to internal hemipelvectomy patients, patients undergoing total sacrectomy had more comorbidities, a higher complication rate, and a worse functional outcome. Conclusion The free fibula flap for spinopelvic reconstruction is safe and effective, and is associated with a high bony union rate and superior functional outcomes. Clinical question/level of evidence Risk, III.

Objective To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. Summary of background data The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. Methods The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. Results We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. Conclusions Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

Study design Systematic literature review. Objective To investigate if evidence-based principles of oncologic resection for primary spinal tumors are correlated with an acceptable morbidity and mortality profile and satisfactory health-related quality of life (HRQOL) measures. Summary of background data Respecting oncologic principles for primary spinal tumor surgery is correlated with lower recurrence rates. These interventions are, however, often highly morbid. Methods A systematic literature review was performed to address the objectives by searching MEDLINE and EBMR databases. Articles that met our inclusion criteria were reviewed. GRADE guidelines were used for recommendation formulation. Results A total of 25 articles addressing the morbidity and mortality profile of primary spinal tumor surgery were identified. For sacral tumors, complication rates of up to 100% have been reported and complication-related death ranged from 0% to 27%. Mobile spine tumor complication rates varied from 13% to 73.7% and complication-related death ranged from 0% to 7.7%. Seven articles examining HRQOL for this patient population were identified. The limited literature showed comparable patient HRQOL profiles to those with benign conditions such as degenerative disc disease. Conclusion Respecting oncologic principles for primary spinal tumors are correlated with high adverse event rates. We recommend that primary spinal tumor surgeries be performed in experienced centers with multidisciplinary support teams and that prospective adverse event collection be promoted (strong recommendation/very low certainty of the evidence). Oncologic resection of primary tumors of the spine is associated with HRQOL that more closely approximates normative values with increasing duration of follow-up, but decreases with disease recurrence. We recommend primary spinal tumor surgery be performed with a curative intent whenever possible, even at the expense of greater initial morbidity to optimize long-term HRQOL (strong recommendation/very low certainty of the evidence). Level of evidence N/A.

Study design Systematic literature review and expert survey OBJECTIVE.: The aim of this study was to determine factors associated with neurologic improvement in patients with neurologic deficits secondary to metastatic epidural spinal cord compression (MESCC). Clear understanding of these factors will guide surgical decision-making by helping to elucidate which patients are more likely to benefit from surgery and how surgeons can increase the probability of neurologic and functional restoration. Summary of background data Surgical spinal cord decompression has been shown to improve neurologic function in patients with symptomatic MESCC. However, prognostication of neurologic improvement after surgery remains challenging, owing to sparse data and complexity of these patients. Methods PubMed and Embase databases were searched for relevant publications. PRISMA Statement guided publication selection and data reporting. GRADE guidelines were used for evidence quality evaluation and recommendation formulation. Results Low-quality evidence supports the use of the duration and severity of neurologic deficit as predictors of neurological recovery in patients with MESCC. Low-quality evidence supports the use of thoracic level of compression and previous irradiation as adverse predictors of neurological recovery. Nearly all of the AOSpine Knowledge Forum Tumor members who responded to the survey agreed that ambulation with assistance represented a successful surgical result and that duration of ambulation loss and the severity of weakness should be considered when trying to predict whether surgery would result in restoration of ambulation. Conclusions Review of literature and expert opinion support the importance of duration of ambulation loss and the severity of neurologic deficit (muscle strength, bladder function) in prediction of neurologic recovery among patients with symptomatic MESCC. Efforts to reduce the duration of ambulation loss and to prevent progression of neurologic deficits should be made to improve the probability of neurologic recovery. Level of evidence 2.

Background Stroke is the third leading cause of death among US Hispanic and non‐Hispanic black women aged 65 and older. One factor that may protect against stroke is breastfeeding. Few studies have assessed the association between breastfeeding and stroke and whether this association differs by race and ethnicity. Methods and Results Data were taken from the Women's Health Initiative Observational Study with follow‐up through 2010; adjusted hazard ratios for stroke subsequent to childbirth were estimated with Cox regression models accounting for left and right censoring, overall and stratified by race/ethnicity. Of the 80 191 parous women in the Women's Health Initiative Observational Study, 2699 (3.4%) had experienced a stroke within a follow‐up period of 12.6 years. The average age was 63.7 years at baseline. Fifty‐eight percent (n=46 699) reported ever breastfeeding; 83% were non‐Hispanic white, 8% were non‐Hispanic black, 4% were Hispanic, and 5% were of other race/ethnicity. After adjustment for nonmodifiable potential confounders, compared with women who had never breastfed, women who reported ever breastfeeding had a 23% lower risk of stroke (adjusted hazard ratio=0.77; 95% confidence interval 0.70‐0.83). This association was strongest for non‐Hispanic black women (adjusted hazard ratio=0.52; 95% confidence interval 0.37‐0.71). Further, breastfeeding for a relatively short duration (1‐6 months) was associated with a 19% lower risk of stroke (adjusted hazard ratios=0.81; 95% confidence interval 0.74‐0.89). This association appeared stronger with longer breastfeeding duration and among non‐Hispanic white and non‐Hispanic black women (test for trend P< 0.01). Conclusions Study results show an association and dose‐response relationship between breastfeeding and lower risk of stroke among postmenopausal women after adjustment for multiple stroke risk factors and lifestyle variables. Further investigation is warranted.

Supplemental Digital Content is available in the text., Background: Patients undergoing surgeries involving extensive posterior spine instrumentation and fusion often have multiple risk factors for wound healing complications. We performed a systematic review and meta-analysis of the available evidence on immediate (proactive/prophylactic) and delayed (reactive) spinal wound reconstruction. We hypothesized that immediate soft-tissue reconstruction of extensive spinal wounds would be associated with fewer postoperative surgicalsite complications than delayed reconstruction. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a PubMed database search was performed to identify English-language, human-subject literature published between 2003 and 2018. Data were summarized, and the pooled prevalence of various wound complications was calculated, weighted by study size, using the generic inverse variance method. A subgroup analysis of all studies with a comparison group (Oxford Centre for Evidence-based Medicine level 3 or better) was performed, and Forest plots were created. Results: The database search yielded 16 articles including 828 patients; 428 (51.7%) received an immediate spinal wound reconstruction and 400 (48.3%) had a delayed reconstruction. Spinal neoplasm was the most common index diagnosis. Paraspinous muscle flap reconstruction was performed in the majority of cases. Pooled analysis of all studies revealed immediate reconstruction to be associated with decreased rates of overall wound complications (28.5% versus 18.8%), hardware loss (10.7% versus 1.8%), and wound infections (10.7% versus 7.6%) compared with delayed reconstruction. Conclusions: Immediate soft-tissue reconstruction of high-risk spinal wounds is associated with fewer wound healing complications and increased hardware retention.

Background— Vascular inflammation and lipid deposition are prominent features of atherosclerotic lesion formation. We have shown previously that the dithiol compound α-lipoic acid (LA) exerts antiinflammatory effects by inhibiting tumor necrosis factor-α– and lipopolysaccharide-induced endothelial and monocyte activation in vitro and lipopolysaccharide-induced acute inflammatory responses in vivo. Here, we investigated whether LA inhibits atherosclerosis in apolipoprotein E–deficient (apoE −/− ) and apoE/low-density lipoprotein receptor–deficient mice, 2 well-established animal models of human atherosclerosis. Methods and Results— Four-week–old female apoE −/− mice (n=20 per group) or apoE/low-density lipoprotein receptor–deficient mice (n=21 per group) were fed for 10 weeks a Western-type chow diet containing 15% fat and 0.125% cholesterol without or with 0.2% (wt/wt) R,S -LA or a normal chow diet containing 4% fat without or with 0.2% (wt/wt) R -LA, respectively. Supplementation with LA significantly reduced atherosclerotic lesion formation in the aortic sinus of both mouse models by ≈20% and in the aortic arch and thoracic aorta of apoE −/− and apoE/low-density lipoprotein receptor–deficient mice by ≈55% and 40%, respectively. This strong antiatherogenic effect of LA was associated with almost 40% less body weight gain and lower serum and very low-density lipoprotein levels of triglycerides but not cholesterol. In addition, LA supplementation reduced aortic expression of adhesion molecules and proinflammatory cytokines and aortic macrophage accumulation. These antiinflammatory effects of LA were more pronounced in the aortic arch and the thoracic aorta than in the aortic sinus, reflecting the corresponding reductions in atherosclerosis. Conclusions— Our study shows that dietary LA supplementation inhibits atherosclerotic lesion formation in 2 mouse models of human atherosclerosis, an inhibition that appears to be due to the “antiobesity,” antihypertriglyceridemic, and antiinflammatory effects of LA. LA may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases.

Background: Short-term quality improvement (QI) interventions for depression can improve long-term mental health but mechanisms are unknown. We hypothesized that 1 pathway for such health benefits was an indirect effect with QI reducing risk factors for depression such as stressful life events. Objective: To determine whether 6-12 month QI programs for depression reduce negative life events at 5-year follow-up and to model the relationship between program implementation, life events and mental health over 9 years. Design: Forty-six primary care clinics in 6 managed care organizations were randomized to usual care or 1 of 2 QI interventions. We focus on the intervention that provided resources to assess and manage depression while particularly facilitating access to evidence-based psychotherapy ("QI-Therapy"). Subjects: A total of 1300 enrolled patients with current depressive symptoms, who had data at any of 4 data points: baseline, or follow-up year 1, 5, or 9. Measures: Total and negatively-evaluated life events and psychologic well-being. Results: A path model showed that QI-Therapy, in addition to improving psychologic well-being at year 1 (P = 0.0033), reduced negative life events at year 5 (P = 0.0033). This effect was not fully explained by improved psychologic well-being. Better mental health (P < 0.0001) and fewer negative life events (P = 0.0013) at year 5 were associated with improved psychologic well-being at 9 years. Conclusions: Depression QI programs that include resources for psychotherapy can reduce occurrence of life events, further protecting subsequent mental health. Implications for the design of QI programs and development of prevention interventions are discussed.

Transgenic mice (T26) bearing the envelope, regulatory, and accessory genes of HIV- I develop renal disease resembling human HIV-associated nephropathy (HIVAN). Effects of vehicle (VEH) and the angiotensin-converting enzyme inhibitor captopril (CAP) were examined in wild-type (WT) or T26 mice treated from 7 to 100 d of age. Mortality was lower in CAP T26 mice (30 mg/kg: 8%; 100 mg/kg: 12%) than VEH T26 mice (52%). The urinary protein/creatinine ratio was increased in VEH T26 mice (19.5+/-7.60) versus WT mice (6.1+/-0.83), but not in low-dose (7.3+/-0.94) or high-dose (8.2+/-1.02) CAP T26 mice. Blood urea nitrogen was higher in VEH T26 mice (52+/-16.2 mg/dl) than VEH WT mice (24+/-0.8). Blood urea nitrogen was also elevated in CAP WT (high dose: 43+/-2.1 mg/dl) and T26 mice (high dose: 42+/-2.4 mg/dl). Glomerular injury was higher in VEH T26 mice (6.8+/-0.58) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 1.1+/-0.17; high dose: 0.7+/-0.13). Tubulointerstitial injury was also greater in VEH T26 mice (1.1+/-0.10) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 0.4+/-0.10; high dose: 0.3+/-0.10). These data validate recent nonrandomized studies of captopril in HIV-infected patients, and suggest that an angiotensin-converting enzyme substrate is an important mediator in HIVAN. A randomized placebo-controlled trial of captopril in HIVAN may be warranted.

Renal effects of endothelin (ET)-3 have been described in normotensive but not spontaneously hypertensive rats (SHR). Infusion (170 ng/kg/min) of the ETB receptor selective agonists ET-3 and sarafotoxin S6c (SS6c) was used to investigate ETB receptor modulation of renal function in SHR. ET-3 decreased glomerular filtration rate (GFR) and renal plasma flow (RPF) by approximately 95% (0.1 +/- 0.01 and 0.1 +/- 0.02 ml/min, respectively) versus vehicle (1.3 +/- 0.08 and 3.6 +/- 0.23, respectively) in SHR. ET-3 exerted a biphasic effect on urine flow (UV); an initial increase and then a decrease (vehicle, 4.2 +/- 0.55; ET-3, 0.2 +/- 0.09 microliter/min). ET-3 increased mean arterial pressure (vehicle, 159 +/- 4.1; ET-3, 174 +/- 3.1 mm Hg). SS6c decreased GFR and RPF by approximately 60% (0.8 +/- 0.12 and 2.0 +/- 0.18 ml/min, respectively) versus vehicle (2.0 +/- 0.19 and 5.2 +/- 0.45, respectively). UV did not change. Depressor effects of SS6c were observed (vehicle, 154 +/- 1.5; SS6c, 127 +/- 3.1 mm Hg). The ETB receptor selective agonists ET-3 and SS6c markedly decreased GFR and RPF in SHR, suggesting that endogenous ET-3 may modulate renal function through ETB receptors in SHR.

We previously described delayed pressor response (DPR) 3 h after endothelin (ET)-1 injection in normotensive rats. In the current study, we examined effects of the ETA receptor antagonist BQ123 (0.01 mumol/kg/min intravenously, i.v.), phosphoramidon (100 mumol/kg i.v.), the neutral endopeptidase inhibitor SQ28603 (112 mumol/kg + 0.04 mumol/kg/min i.v.), the angiotensin-converting enzyme inhibitor enalaprilat (10 mumol/kg i.v.), and the thromboxane receptor antagonist, SQ29548 (0.5 mumol/kg + 0.5 mumol/kg/h i.v.) on DPR. Vehicle and ET-1 (1.0 nmol/kg i.v.) were administered on day 1; vehicle or drug and ET-1 were administered on day 2. BQ123 inhibited DPR 36% (vehicle 44 +/- 5, BQ123 28 +/- 3 mm Hg); phosphoramidon inhibited DPR 56% (vehicle 45 +/- 4, and phosphoramidon 20 +/- 5 mm Hg). DPR was unchanged after SQ28603 (vehicle 39 +/- 2 and SQ28603 44 +/- 2 mm Hg), enalaprilat (vehicle 39 +/- 2 and enalaprilat 38 +/- 7 mm Hg), or SQ29548 (vehicle 46 +/- 6 and SQ29548 43 +/- 3 mm Hg). The results suggest that DPR 3 h after ET-1 injection in rats is mediated in part through ETA receptors. DPR does not appear to involve thromboxane or synthesis of angiotensin II (AII), but may be related to synthesis of ET-1.

The ETA receptor antagonist, BQ 123 was used to characterize depressor and initial and delayed pressor responses to ET-1 in conscious rats. BQ 123 (0.001-0.01 mumol/kg/min) dose-dependently inhibited the initial ET-1 (0.1 nmol/kg) pressor response, reaching a maximum after 0.01 BQ 123 (61 +/- 4% inhibition). Less inhibition of the pressor effects occurred after higher doses of BQ 123 (1: 10 +/- 6% inhibition). The depressor response to 1 nmol/kg ET-1 was unchanged by BQ 123 (0.01), but inhibited by BQ 123 (1). The initial pressor response to 1.0 nmol/kg ET-1 was inhibited by BQ 123 (0.01: 26 +/- 6%; 1.0: 41 +/- 3% inhibition). The delayed pressor response, 180 min post-ET-1 (+41 +/- 2% increase) was reduced by BQ 123 infused before the delayed peak (+14 +/- 5% increase). Plasma immunoreactive ET values were: control: 5.4 +/- 0.4; initial peak: 491.4 +/- 50.6; delayed peak: 8.2 +/- 0.6 fmol/ml. The delayed ET-1 response does not coincide with sustained high circulating levels of immunoreactive ET, but inhibition of the response by BQ 123 suggests that it may involve endothelin receptors.

Changes in tonic accommodation and tonic vergence were studied as a function of stimulus duration and time after near fixation. Thirteen visually normal young adults each participated in experimental sessions comprising each of 12 combinations of stimulus type (accommodative or vergence) and stimulus duration (0.25, 0.5, 1, 2, 4, or 8 min). During each session, measurements were made of either tonic accommodation or tonic vergence 30 s before stimulus onset and at 0.5, 2, 4, 6, 8, 10, 12, and 14 min after stimulus offset. The stimulus (a high contrast reduced Snellen visual acuity chart) was viewed monocularly at the accommodative nearpoint and binocularly through pinholes at the fusional nearpoint on the accommodative and vergence sessions, respectively. For tonic accommodation, stimulus duration had no significant effect on either the magnitude of the aftereffect or its rate of decay. For tonic vergence however, the aftereffect was larger and had a slower rate of decay as stimulus duration increased. The results suggest that the adaptive mechanisms within the two systems have different time constants.

Background: In growing children, an expandable endoprosthesis is commonly used after distal femoral resection to compensate for loss of the distal femoral physis. Our hypothesis was that such prostheses can affect proximal tibial growth, which would contribute to an overall leg-length discrepancy and cause angular deformity. Methods: Twenty-three skeletally immature patients underwent the placement of a distal femoral expandable endoprosthesis between 1994 and 2012. Tibial length, femoral length, and mechanical axis were measured radiographically to determine the growth rate. Results: No patient had radiographic evidence of injury to the proximal tibial physis at the time of surgery other than insertion of the tibial stem. Fifteen (65%) of the patients experienced less proximal tibial growth in the operative compared with the contralateral limb. In ten (43%) of the patients, the discrepancy progressively worsened, whereas in five (22%) of the patients, the discrepancy stabilized. Seven patients did not develop tibial length discrepancy, and one patient had overgrowth of the tibia. For the ten patients with progressive shortening, the proximal tibial physis grew an average of 4.0 mm less per year in the operative limb. Five (22%) of the patients had ≥20 mm of tibial length discrepancy at last follow-up. Three of these patients underwent contralateral tibial epiphysiodesis. Three patients required corrective surgery for angular deformity. Conclusions: The tibial growth plate may not resume normal growth after implantation of a distal femoral prosthesis. Physeal bar resection, prosthesis revision, and contralateral tibial epiphysiodesis may be needed to address tibial growth abnormalities. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.