Changes in vaccination uptake against pneumococcal disease, influenza, and coronavirus disease 2019 (COVID-19) before and after a Head and Neck cancer diagnosis.

BACKGROUND: Pneumonia is one of the main contributors to non-cancer mortality among patients with head and neck cancer (HNC). This study aimed to determine the vaccine uptake for pneumococcal polysaccharide and conjugate vaccines, quadrivalent influenza vaccines, and mRNA COVID-19 vaccines before and after an HNC diagnosis. Furthermore, the study investigated the timing of vaccination after a cancer diagnosis. MATERIALS & METHODS: This register based multicentre study included Danish patients ≥ 18y diagnosed with HNC between 2018 and 2021. The vaccine uptake was assessed by calculating cumulative incidence (CI), while the timing of vaccination after an HNC diagnosis was explored by calculating incidence rates of vaccination the first and second half year after a cancer diagnosis. RESULTS: The cumulative incidence of vaccine uptake for pneumococcal vaccines was estimated to be 8 % and 16 % one year before and after an HNC diagnosis, respectively. The CIs were 36 % and 38 % for quadrivalent influenza vaccines, respectively, whereas the CIs of vaccine uptake for mRNA COVID-19 vaccines were 60 % and 89 %. The IR of mRNA COVID-19 vaccinations the first half year after HNC diagnosis were 273 per 1000 person-months of follow-up (PMFU) and 111 per 1000 PMFU the second half year, respectively (IRR: 0.38, p < 0.001). Comparing the same periods, the IR of quadrivalent influenza vaccination was 28 per 1000 PMFU and 51 per 1000 PMFU (IRR: 1.95, 0 < 0.001). The IRs of pneumococcal vaccinations were 11 per 1000 PMFU and 14 per 1000 PMFU (IRR 1.28, p = 0.21). CONCLUSIONS: Although our study shows a significant increase in pneumococcal and COVID-19 vaccine uptake after HNC diagnosis, a gap remains in vaccine uptake before diagnosis, underscoring the need for increased awareness of vaccination options and recommendations. Our findings could serve as a reference for future recommendations.

What is the effect of preoperative depression on outcomes after minimally invasive surgery for adult spinal deformity? A prospective cohort analysis.

OBJECTIVE: Depression has been implicated with worse immediate postoperative outcomes in adult spinal deformity (ASD) correction, yet the specific impact of depression on those patients undergoing minimally invasive surgery (MIS) requires further clarity. This study aimed to evaluate the role of depression in the recovery of patients with ASD after undergoing MIS. METHODS: Patients who underwent MIS for ASD with a minimum postoperative follow-up of 1 year were included from a prospectively collected, multicenter registry. Two cohorts of patients were identified that consisted of either those affirming or denying depression on preoperative assessment. The patient-reported outcome measures (PROMs) compared included scores on the Oswestry Disability Index (ODI), numeric rating scale (NRS) for back and leg pain, Scoliosis Research Society Outcomes Questionnaire (SRS-22), SF-36 physical component summary, SF-36 mental component summary (MCS), EQ-5D, and EQ-5D visual analog scale. RESULTS: Twenty-seven of 147 (18.4%) patients screened positive for preoperative depression. The nondepressed cohort had an average of 4.83 levels fused, and the depressed cohort had 5.56 levels fused per patient (p = 0.267). At 1-year follow-up, 10 patients still reported depression, representing a 63% decrease. Postoperatively, both cohorts demonstrated improvement in their PROMs; however, at 1-year follow-up, those without depression had statistically better outcomes based on the EQ-5D, MCS, and SRS-22 scores (p < 0.05). Patients with depression continued to experience higher NRS leg scores at 1-year follow-up (3.63 vs 2.22, p = 0.018). After controlling for covariates, the authors found that depression significantly impacted only 1-year follow-up MCS scores (ß = 8.490, p < 0.05). CONCLUSIONS: Depressed and nondepressed patients reported similar improvements after MIS surgery, except MCS scores were more likely to improve in nondepressed patients.

Greater improvement in Neck Disability Index scores in women after surgery for cervical myelopathy: an analysis of the Quality Outcomes Database.

OBJECTIVE: There is a high prevalence of cervical myelopathy that requires surgery; as such, it is important to identify how different groups benefit from surgery. The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry, that includes demographic, clinical, and patient-reported outcome data to measure the safety and quality of neurosurgical procedures. In this study, the authors assessed the impact of gender on patient-reported outcomes in patients who underwent surgery for cervical myelopathy. METHODS: The authors analyzed 1152 patients who underwent surgery for cervical myelopathy and were included in the QOD cervical module. Univariate comparison of baseline patient characteristics between males and females who underwent surgery for cervical spondylotic myelopathy was performed. Baseline characteristics that significantly differed between males and females were included in a multivariate generalized linear model comparing baseline and 1-year postoperative Neck Disability Index (NDI) scores. RESULTS: This study included 546 females and 604 males. Females demonstrated significantly greater improvement in NDI score 1 year after surgery (p = 0.036). In addition to gender, the presence of axial neck pain and insurance status were also significantly predictive of improvement in NDI score after surgery (p = 0.0013 and p = 0.0058, respectively). CONCLUSIONS: Females were more likely to benefit from surgery for cervical myelopathy compared with males. It is important to identify gender differences in postoperative outcomes after surgery in order to deliver more personalized and patient-centric care.

Three-level ACDF versus 3-level laminectomy and fusion: are there differences in outcomes? An analysis of the Quality Outcomes Database cervical spondylotic myelopathy cohort.

OBJECTIVE: The authors sought to compare 3-level anterior with posterior fusion surgical procedures for the treatment of multilevel cervical spondylotic myelopathy (CSM). METHODS: The authors analyzed prospective data from the 14 highest enrolling sites of the Quality Outcomes Database CSM module. They compared 3-level anterior cervical discectomy and fusion (ACDF) and posterior cervical laminectomy and fusion (PCF) surgical procedures, excluding surgical procedures crossing the cervicothoracic junction. Rates of reaching the minimal clinically important difference (MCID) in patient-reported outcomes (PROs) were compared at 24 months postoperatively. Multivariable analyses adjusted for potential confounders elucidated in univariable analysis. RESULTS: Overall, 199 patients met the inclusion criteria: 123 ACDF (61.8%) and 76 PCF (38.2%) patients. The 24-month follow-up rates were similar (ACDF 90.2% vs PCF 92.1%, p = 0.67). Preoperatively, ACDF patients were younger (60.8 ± 10.2 vs 65.0 ± 10.3 years, p < 0.01), and greater proportions were privately insured (56.1% vs 36.8%, p = 0.02), actively employed (39.8% vs 22.8%, p = 0.04), and independently ambulatory (14.6% vs 31.6%, p < 0.01). Otherwise, the cohorts had equivalent baseline modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), numeric rating scale (NRS)-arm pain, NRS-neck pain, and EQ-5D scores (p > 0.05). ACDF patients had reduced hospitalization length (1.6 vs 3.9 days, p < 0.01) and a greater proportion had nonroutine discharge (7.3% vs 22.8%, p < 0.01), but they had a higher rate of postoperative dysphagia (13.5% vs 3.5%, p = 0.049). Compared with baseline values, both groups demonstrated improvements in all outcomes at 24 months (p < 0.05). In multivariable analyses, after controlling for age, insurance payor, employment status, ambulation status, and other potential clinically relevant confounders, ACDF was associated with a greater proportion of patients with maximum satisfaction on the North American Spine Society Patient Satisfaction Index (NASS) (NASS score of 1) at 24 months (69.4% vs 53.7%, OR 2.44, 95% CI 1.17-5.09, adjusted p = 0.02). Otherwise, the cohorts shared similar 24-month outcomes in terms of reaching the MCID for mJOA, NDI, NRS-arm pain, NRS-neck pain, and EQ-5D score (adjusted p > 0.05). There were no differences in the 3-month readmission (ACDF 4.1% vs PCF 3.9%, p = 0.97) and 24-month reoperation (ACDF 13.5% vs PCF 18.6%, p = 0.36) rates. CONCLUSIONS: In a cohort limited to 3-level fusion surgical procedures, ACDF was associated with reduced blood loss, shorter hospitalization length, and higher routine home discharge rates; however, PCF resulted in lower rates of postoperative dysphagia. The procedures yielded comparably significant improvements in functional status (mJOA score), neck and arm pain, neck pain-related disability, and quality of life at 3, 12, and 24 months. ACDF patients had significantly higher odds of maximum satisfaction (NASS score 1). Given comparable outcomes, patients should be counseled on each approach's complication profile to aid in surgical decision-making.

Incremental benefits of circumferential minimally invasive surgery for increasingly frail patients with adult spinal deformity.

OBJECTIVE: Circumferential minimally invasive surgery (cMIS) may provide incremental benefits compared with open surgery for patients with increasing frailty status by decreasing peri- and postoperative complications. METHODS: Operative patients with adult spinal deformity (ASD) ≥ 18 years old with baseline and 2-year postoperative data were assessed. With propensity score matching, patients who underwent cMIS (cMIS group) were matched with similar patients who underwent open surgery (open group) based on baseline BMI, C7-S1 sagittal vertical axis, pelvic incidence to lumbar lordosis mismatch, and S1 pelvic tilt. The Passias modified ASD frailty index (mASD-FI) was used to determine patient frailty stratification as not frail, frail, or severely frail. Baseline and postoperative factors were assessed using two-way analysis of covariance (ANCOVA) and multivariate ANCOVA while controlling for baseline age, Charlson Comorbidity Index (CCI) score, and number of levels fused. RESULTS: After propensity score matching, 170 ASD patients (mean age 62.71 ± 13.64 years, 75.0% female, mean BMI 29.25 ± 6.60 kg/m2) were included, split evenly between the cMIS and open groups. Surgically, patients in the open group had higher numbers of posterior levels fused (p = 0.021) and were more likely to undergo three-column osteotomies (p > 0.05). Perioperatively, cMIS patients had lower intraoperative blood loss and decreased use of cell saver across frailty groups (with adjustment for baseline age, CCI score, and levels fused), as well as fewer perioperative complications (p < 0.001). Adjusted analysis also revealed that compared to open patients, increasingly frail patients in the cMIS group were also more likely to demonstrate greater improvement in 1- and 2-year postoperative scores for the Oswestry Disability Index, SRS-36 (total), EQ-5D and SF-36 (all p < 0.05). With regard to postoperative complications, increasingly frail patients in the cMIS group were also noted to experience significantly fewer complications overall (p = 0.036) and fewer major intraoperative complications (p = 0.039). The cMIS patients were also less likely to need a reoperation than their open group counterparts (p = 0.043). CONCLUSIONS: Surgery performed with a cMIS technique may offer acceptable outcomes, with diminishment of perioperative complications and mitigation of catastrophic outcomes, in increasingly frail patients who may not be candidates for surgery using traditional open techniques. However, further studies should be performed to investigate the long-term impact of less optimal alignment in this population.

Spinal Deformity Complexity Checklist for Minimally Invasive Surgery: Expert Consensus from the Minimally Invasive International Spine Study Group.

BACKGROUND: We developed a spinal deformity complexity checklist (SDCC) to assess the difficulty in performing a circumferential minimally invasive surgery (MIS) for adult spinal deformity. METHODS: A modified Delphi method of panel experts was used to construct an SDCC checklist of radiographic and patient-related characteristics that could affect the complexity of surgery via MIS approaches. Ten surgeons with expertise in MIS deformity surgery were queried to develop and refine the SDCC with 3 radiographic categories (x-ray, magnetic resonance imaging, computed tomography) and 1 patient-related category. Within each category, characteristics affecting MIS complexity were identified by initial roundtable discussion. Second-round discussion determined which characteristics substantially impacted complexity the most. RESULTS: Thirteen characteristics within the x-ray category were determined. Spinopelvic characteristics, endpoints of instrumentation, and prior hardware/fusion were associated with increased complexity. Vertebral body rotation-as reflected by the Nash-Moe grade-added significant complexity. Psoas anatomy and spinal stenosis added the most complexity for the 5 magnetic resonance imaging characteristics. There were 3 characteristics in the CT category with pre-exisiting fusion, being the variable most highly selected. Of the 5 patient-related characteristics, osteoporosis and BMI were found to most affect complexity. CONCLUSIONS: The SDCC is a comprehensive list of pertinent radiographic and patient-related characteristics affecting complexity level for MIS deformity surgery. The value of the SDCC is that it allows rapid assessment of key factors when determining whether MIS surgery can be performed effectively and safely. Patients with scores of 4 in any characteristic should be considered challenging to treat with MIS; open surgery may be a better alternative.

Use of an exoscope for enhanced visualization of a Schwab grade 5 osteotomy to correct kyphotic deformity.

The development of the 3D exoscope has advanced intraoperative visualization by providing access to visual corridors that were previously difficult to obtain or maintain with traditional operating microscopes. Favorable ergonomics, maneuverability, and increased potential for instruction provide utility in a large range of procedures. Here, the authors demonstrate the exoscope system in a patient with progressive thoracolumbar junctional kyphosis with bony retropulsion of a T12-L1 fracture requiring a Schwab grade 5 osteotomy and fusion. The utilization of the exoscope provides visual access to the ventrolateral dura for the entire surgical team (surgeons, learners, and scrub nurse). The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21190.

Role of obesity in less radiographic correction and worse health-related quality-of-life outcomes following minimally invasive deformity surgery.

OBJECTIVE: Minimally invasive surgery (MIS) for adult spinal deformity (ASD) can offer deformity correction with less tissue manipulation and damage. However, the impact of obesity on clinical outcomes and radiographic correction following MIS for ASD is poorly understood. The goal of this study was to determine the role, if any, that obesity has on radiographic correction and health-related quality-of-life measures in MIS for ASD. METHODS: Data were collected from a multicenter database of MIS for ASD. This was a retrospective review of a prospectively collected database. Patient inclusion criteria were age ≥ 18 years and coronal Cobb angle ≥ 20°, pelvic incidence-lumbar lordosis mismatch ≥ 10°, or sagittal vertical axis (SVA) > 5 cm. A group of patients with body mass index (BMI) < 30 kg/m2 was the control cohort; BMI ≥ 30 kg/m2 was used to define obesity. Obesity cohorts were categorized into BMI 30-34.99 and BMI ≥ 35. All patients had at least 1 year of follow-up. Preoperative and postoperative health-related quality-of-life measures and radiographic parameters, as well as complications, were compared via statistical analysis. RESULTS: A total of 106 patients were available for analysis (69 control, 17 in the BMI 30-34.99 group, and 20 in the BMI ≥ 35 group). The average BMI was 25.24 kg/m2 for the control group versus 32.46 kg/m2 (p < 0.001) and 39.5 kg/m2 (p < 0.001) for the obese groups. Preoperatively, the BMI 30-34.99 group had significantly more prior spine surgery (70.6% vs 42%, p = 0.04) and worse preoperative numeric rating scale leg scores (7.71 vs 5.08, p = 0.001). Postoperatively, the BMI 30-34.99 cohort had worse Oswestry Disability Index scores (33.86 vs 23.55, p = 0.028), greater improvement in numeric rating scale leg scores (-4.88 vs -2.71, p = 0.012), and worse SVA (51.34 vs 26.98, p = 0.042) at 1 year postoperatively. Preoperatively, the BMI ≥ 35 cohort had significantly worse frailty (4.5 vs 3.27, p = 0.001), Oswestry Disability Index scores (52.9 vs 44.83, p = 0.017), and T1 pelvic angle (26.82 vs 20.71, p = 0.038). Postoperatively, after controlling for differences in frailty, the BMI ≥ 35 cohort had significantly less improvement in their Scoliosis Research Society-22 outcomes questionnaire scores (0.603 vs 1.05, p = 0.025), higher SVA (64.71 vs 25.33, p = 0.015) and T1 pelvic angle (22.76 vs 15.48, p = 0.029), and less change in maximum Cobb angle (-3.93 vs -10.71, p = 0.034) at 1 year. The BMI 30-34.99 cohort had significantly more infections (11.8% vs 0%, p = 0.004). The BMI ≥ 35 cohort had significantly more implant complications (30% vs 11.8%, p = 0.014) and revision surgery within 90 days (5% vs 1.4%, p = 0.034). CONCLUSIONS: Obese patients who undergo MIS for ASD have less correction of their deformity, worse quality-of-life outcomes, more implant complications and infections, and an increased rate of revision surgery compared with their nonobese counterparts, although both groups benefit from surgery. Appropriate counseling should be provided to obese patients.

Two- and three-year outcomes of minimally invasive and hybrid correction of adult spinal deformity.

OBJECTIVE: Previous studies have demonstrated the short-term radiographic and clinical benefits of circumferential minimally invasive surgery (cMIS) and hybrid (i.e., minimally invasive anterior or lateral interbody fusion with an open posterior approach) techniques to correct adult spinal deformity (ASD). However, it is not known if these benefits are maintained over longer periods of time. This study evaluated the 2- and 3-year outcomes of cMIS and hybrid correction of ASD. METHODS: A multicenter database was retrospectively reviewed for patients undergoing cMIS or hybrid surgery for ASD. Patients were ≥ 18 years of age and had one of the following: maximum coronal Cobb angle (CC) ≥ 20°, sagittal vertical axis (SVA) > 5 cm, pelvic incidence-lumbar lordosis mismatch (PI-LL) ≥ 10°, or pelvic tilt (PT) > 20°. Radiographic parameters were evaluated at the latest follow-up. Clinical outcomes were compared at 2- and 3-year time points and adjusted for age, preoperative CC, levels operated, levels with interbody fusion, presence of L5-S1 anterior lumbar interbody fusion, and upper and lower instrumented vertebral level. RESULTS: Overall, 197 (108 cMIS, 89 hybrid) patients were included with 187 (99 cMIS, 88 hybrid) and 111 (60 cMIS, 51 hybrid) patients evaluated at 2 and 3 years, respectively. The mean (± SD) follow-up duration for cMIS (39.0 ± 13.3 months, range 22-74 months) and hybrid correction (39.9 ± 16.8 months, range 22-94 months) were similar for both cohorts. Hybrid procedures corrected the CC greater than the cMIS technique (adjusted p = 0.022). There were no significant differences in postoperative SVA, PI-LL, PT, and sacral slope (SS). At 2 years, cMIS had lower Oswestry Disability Index (ODI) scores (adjusted p < 0.001), greater ODI change as a percentage of baseline (adjusted p = 0.006), less visual analog scale (VAS) back pain (adjusted p = 0.006), and greater VAS back pain change as a percentage of baseline (adjusted p = 0.001) compared to hybrid techniques. These differences were no longer significant at 3 years. At 3 years, but not 2 years, VAS leg pain was lower for cMIS compared to hybrid techniques (adjusted p = 0.032). Those undergoing cMIS had fewer overall complications compared to hybrid techniques (adjusted p = 0.006), but a higher odds of pseudarthrosis (adjusted p = 0.039). CONCLUSIONS: In this review of a multicenter database for patients undergoing cMIS and hybrid surgery for ASD, hybrid procedures were associated with a greater CC improvement compared to cMIS techniques. cMIS was associated with superior ODI and back pain at 2 years, but this difference was no longer evident at 3 years. However, cMIS was associated with superior leg pain at 3 years. There were fewer complications following cMIS, with the exception of pseudarthrosis.

Awake spinal surgery: simplifying the learning curve with a patient selection algorithm.

OBJECTIVE: There is a learning curve for surgeons performing "awake" spinal surgery. No comprehensive guidelines have been proposed for the selection of ideal candidates for awake spinal fusion or decompression. The authors sought to formulate an algorithm to aid in patient selection for surgeons who are in the startup phase of awake spinal surgery. METHODS: The authors developed an algorithm for selecting patients appropriate for awake spinal fusion or decompression using spinal anesthesia supplemented with mild sedation and local analgesia. The anesthetic protocol that was used has previously been reported in the literature. This algorithm was formulated based on a multidisciplinary team meeting and used in the first 15 patients who underwent awake lumbar surgery at a single institution. RESULTS: A total of 15 patients who underwent decompression or lumbar fusion using the awake protocol were reviewed. The mean patient age was 61 ± 12 years, with a median BMI of 25.3 (IQR 2.7) and a mean Charlson Comorbidity Index of 2.1 ± 1.7; 7 patients (47%) were female. Key patient inclusion criteria were no history of anxiety, 1 to 2 levels of lumbar pathology, moderate stenosis and/or grade I spondylolisthesis, and no prior lumbar surgery at the level where the needle is introduced for anesthesia. Key exclusion criteria included severe and critical central canal stenosis or patients who did not meet the inclusion criteria. Using the novel algorithm, 14 patients (93%) successfully underwent awake spinal surgery without conversion to general anesthesia. One patient (7%) was converted to general anesthesia due to insufficient analgesia from spinal anesthesia. Overall, 93% (n = 14) of the patients were assessed as American Society of Anesthesiologists class II, with 1 patient (7%) as class III. The mean operative time was 115 minutes (± 60 minutes) with a mean estimated blood loss of 46 ± 39 mL. The median hospital length of stay was 1.3 days (IQR 0.1 days). No patients developed postoperative complications and only 1 patient (7%) required reoperation. The mean Oswestry Disability Index score decreased following operative intervention by 5.1 ± 10.8. CONCLUSIONS: The authors propose an easy-to-use patient selection algorithm with the aim of assisting surgeons with patient selection for awake spinal surgery while considering BMI, patient anxiety, levels of surgery, and the extent of stenosis. The algorithm is specifically intended to assist surgeons who are in the learning curve of their first awake spinal surgery cases.

Cost-effectiveness of ribociclib plus endocrine therapy versus placebo plus endocrine therapy in HR-positive, HER2-negative breast cancer.

BACKGROUND: The 2015 American Society of Clinical Oncology guidelines recommend first-line treatment of hormone receptor (HR)-positive breast cancer with endocrine therapy plus or minus palbociclib, a selective cyclin-dependent kinase (CDK)4/6 inhibitor. In 2018, the U.S. Food and Drug Administration approved ribociclib, a new orally available selective CDK4/6 inhibitor. While gains in progression-free survival (PFS) and overall survival (OS) from ribociclib are important for clinical and treatment outcomes, trade-offs in adverse events (AEs) and additional costs necessitate cost-effectiveness analysis (CEA) to assist consideration by third-party payer systems, physicians, and patients. OBJECTIVES: To (a) develop a Markov model and (b) determine the cost-effectiveness of ribociclib plus endocrine therapy versus endocrine therapy alone as treatment for premenopausal and perimenopausal patients with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: A lifetime 3-state Markov model ("stable," "progressed," and "dead" health states) was developed using a U.S. payer perspective. Transition probabilities were calculated based on OS and PFS outcomes from the randomized controlled phase 3 trial MONALEESA-7. These Kaplan-Meier curves were extended to lifetime by estimating best-fit distributions using loglogistic distribution for ribociclib curves and Weibull distribution for placebo curves. Costs were obtained from national data sources using 2019 U.S. dollars (USD) and discounted by 3%. Utilities were obtained via published breast cancer literature and were included for each health state and for time spent with each AE. Results were expressed as an incremental cost-effectiveness ratio (ICER) expressed as USD per quality-adjusted life-year (QALY) saved. Treatments were assumed to be cost-effective based on a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Base-case, 1-way sensitivity tornado diagrams and probabilistic sensitivity analyses demonstrated changes in the ICER and were driven by the cost of ribociclib and the utility of remaining in the stable health state. RESULTS: Ribociclib plus endocrine therapy was cost-effective at an ICER of $124,513 per QALY when compared with endocrine therapy alone at a WTP threshold of $150,000. The ribociclib plus endocrine therapy arm had an effectiveness of 5.28 QALYs and a total cost of $385,112, while placebo plus endocrine therapy provided only 2.46 QALYs at a lower total cost of $67.246. The model was sensitive to the cost of ribociclib and the utility of time spent in the stable health state. Probabilistic sensitivity analysis demonstrated that endocrine therapy alone was cost-effective until a WTP of $125,000 and was cost-effective 72% of the time at the WTP threshold. CONCLUSIONS: Ribociclib plus endocrine therapy is more cost-effective than endocrine therapy alone. Professionals in managed care settings should consider the pharmacoeconomic benefits of ribociclib for the treatment of HR-positive, HER2-negative breast cancer as they make value-based formulary decisions. Further CEAs should be considered as direct treatment comparison trials between CDK4/6 inhibitors are completed in the future. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Clinical and Radiographic Outcomes After Minimally Invasive Transforaminal Lumbar Interbody Fusion-Early Experience Using a Biplanar Expandable Cage for Lumbar Spondylolisthesis.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) is a surgical technique frequently used to treat symptomatic lumbar spondylolisthesis. We aim to investigate the safety and efficacy of using a biplanar expandable cage in the treatment of symptomatic lumbar spondylolisthesis using a MIS TLIF approach. METHODS: A retrospective review of patient records was performed on patients who underwent MIS TLIF for symptomatic lumbar spondylolisthesis using the FlareHawk cage over a 12-month period. Patient demographics, as well as preoperative and postoperative clinical and radiographic outcome measures were recorded and analyzed. RESULTS: A total of 13 consecutive patients underwent MIS TLIF for symptomatic spondylolisthesis during the study period. The mean age was 60.2 ± 13.9 years, and 61.5% were female. The mean preoperative and postoperative slippage was 7.0 ± 3.0 mm and 1.0 ± 1.9 mm, respectively. The preoperative mean segmental lordosis was 5.1° ± 6.0°, mean anterior, posterior disc, and foraminal height were 9.1 ± 3.9 mm, 5.7 ± 1.5 mm, and 11.0 ± 2.0 mm, respectively. The postoperative mean segmental lordosis was 6.8° ± 4.7°, and mean anterior, posterior disc, and foraminal height were 11.4 ± 2.2 mm, 7.8 ± 1.0 mm, and 12.3 ± 1.3 mm. There was improvement in all radiographic parameters postoperatively. The mean Visual Analog Scale (VAS) back pain, VAS leg pain improved from 7.0 ± 2.9 and 5.1 ± 3.0 preoperatively to 3.1 ± 2.9 and 1.1 ± 1.7 at the latest clinic follow-up visit, respectively (P = .0081). The mean EuroQol-Five Dimensions (EQ5D) score improved from 0.37 ± 1.7 to 0.66 ± 0.23 after surgery. There was no subsidence, endplate violation, cage migration, or other implant-related complications. No patient required reoperation. CONCLUSIONS: The biplanar expandable cage is both safe and efficacious in treating symptomatic lumbar spondylolisthesis using the MIS TLIF approach. Spine surgeons should be familiar with the biplanar expandable cage technology and keep it in their armamentarium in surgical treatment of lumbar spondylolisthesis. LEVEL OF EVIDENCE: 4.

Factors affecting approach selection for minimally invasive versus open surgery in the treatment of adult spinal deformity: analysis of a prospective, nonrandomized multicenter study.

OBJECTIVE: Surgical decision-making and planning is a key factor in optimizing outcomes in adult spinal deformity (ASD). Minimally invasive spinal (MIS) strategies for ASD have been increasingly used as an option to decrease postoperative morbidity. This study analyzes factors involved in the selection of either a traditional open approach or a minimally invasive approach to treat ASD in a prospective, nonrandomized multicenter trial. All centers had at least 5 years of experience in minimally invasive techniques for ASD. METHODS: The study enrolled 268 patients, of whom 120 underwent open surgery and 148 underwent MIS surgery. Inclusion criteria included age ≥ 18 years, and at least one of the following criteria: coronal curve (CC) ≥ 20°, sagittal vertical axis (SVA) > 5 cm, pelvic tilt (PT) > 25°, or thoracic kyphosis (TK) > 60°. Surgical approach selection was made at the discretion of the operating surgeon. Preoperative significant differences were included in a multivariate logistic regression analysis to determine odds ratios (ORs) for approach selection. RESULTS: Significant preoperative differences (p < 0.05) between open and MIS groups were noted for age (61.9 vs 66.7 years), numerical rating scale (NRS) back pain score (7.8 vs 7), CC (36° vs 26.1°), PT (26.4° vs 23°), T1 pelvic angle (TPA; 25.8° vs 21.7°), and pelvic incidence-lumbar lordosis (PI-LL; 19.6° vs 14.9°). No significant differences in BMI (29 vs 28.5 kg/m2), NRS leg pain score (5.2 vs 5.7), Oswestry Disability Index (48.4 vs 47.2), Scoliosis Research Society 22-item questionnaire score (2.7 vs 2.8), PI (58.3° vs 57.1°), LL (38.9° vs 42.3°), or SVA (73.8 mm vs 60.3 mm) were found. Multivariate analysis found that age (OR 1.05, p = 0.002), VAS back pain score (OR 1.21, p = 0.016), CC (OR 1.03, p < 0.001), decompression (OR 4.35, p < 0.001), and TPA (OR 1.09, p = 0.023) were significant factors in approach selection. CONCLUSIONS: Increasing age was the primary driver for selecting MIS surgery. Conversely, increasingly severe deformities and the need for open decompression were the main factors influencing the selection of traditional open surgery. As experience with MIS surgery continues to accumulate, future longitudinal evaluation will reveal if more experience, use of specialized treatment algorithms, refinement of techniques, and technology will expand surgeon adoption of MIS techniques for adult spinal deformity.

Comprehensive genotyping of the C9orf72 hexanucleotide repeat region in 2095 ALS samples from the NINDS collection using a two-mode, long-read PCR assay.

OBJECTIVE: Expansion of the G4C2 repeat tract in the C9orf72 gene is linked to frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we provide comprehensive genotyping of the C9orf72 repeat region for the National Institute of Neurological Disorders and Stroke (NINDS) ALS collection (n = 2095), using a novel bimodal PCR assay capable of amplifying nearly 100% GC-rich sequences. METHODS: A single-tube 3-primer PCR assay mode, resolved using capillary electrophoresis, was used for sizing up to 145 repeats with single-repeat accuracy, for detecting expansions irrespective of their overall size, and for flagging confounding 3' sequence variations (SVs). A modified two-primer PCR mode, resolved via agarose gel electrophoresis, provided further size information for hyper-expanded samples (>145 repeats) up to ∼5.8 kb amplicons (∼950 G4C2 repeats). RESULTS: Within the evaluated cohort, 177 (8.4%) samples were expanded, with 175 (99%) samples being hyper-expanded. 3'-SVs were identified in 64 (3.1%) samples, and were most common in expanded alleles. Genotypes of all 606 (29%) homozygous samples were confirmed using an orthogonal PCR assay. CONCLUSION: This study and PCR method may improve and standardize molecular characterization of the C9orf72 locus, and have the potential to inform phenotype-genotype correlations and therapeutic development in ALS/FTD.

Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department.

STUDY OBJECTIVE: Although validated risk-stratification tools have been used to send low-risk febrile neutropenic patients home from clinic and inpatient settings, there is a dearth of research evaluating these scores in the emergency department (ED). We compare the predictive accuracy of the Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for patients with chemotherapy-induced febrile neutropenia and presenting to the ED. METHODS: We conducted a retrospective cohort study to evaluate all patients with febrile neutropenia (temperature ≥38°C [100.4°F], absolute neutrophil count <1,000 cells/µL) who presented to 2 academic EDs from June 2012 through January 2015. MASCC and CISNE scores were calculated for all subjects, and each visit was evaluated for several outcome variables, including inpatient length of stay, upgrade in level of care, clinical deterioration, positive blood culture results, and death. Descriptive statistics are reported and continuous variables were analyzed with Wilcoxon rank sum. RESULTS: During our study period, 230 patients presented with chemotherapy-induced febrile neutropenia. The CISNE score identified 53 (23%) of these patients as low risk and was highly specific in the identification of a low-risk cohort for all outcome variables (98.3% specific, 95% confidence interval [CI] 89.7% to 99.9%; positive predictive value 98.1%, 95% CI 88.6% to 99.9%). Median length of stay was shorter for low-risk versus high-risk CISNE patients (3-day difference; P<.001). The MASCC score was much less specific (54.2%; 95% CI 40.8% to 67.1%) in the identification of a low-risk cohort. CONCLUSION: Our results suggest that the CISNE score may be the most appropriate febrile neutropenia risk-stratification tool for use in the ED.

A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers.

Stress exposure during early development is known to produce long-term mental health deficits. Stress promotes poor lifestyle choices such as poor diet. Early life adversity and diets high in fat and sugar (HFHS) are known to affect anxiety and memory. However additive effects of HFHS and stress during early development are less explored. Here, we examined whether early life stress (ELS) simulated by limited nesting (LN) induces anxiety-like behaviour and cognitive deficits that are modulated by HFHS diet. We examined key hippocampal markers involved in anxiety and cognition, testing the hypothesis that post-weaning HFHS following ELS would ameliorate anxiety-like behaviour but worsen memory and associated hippocampal changes. Sprague-Dawley rats were exposed to LN, postnatal days 2-9, and at weaning, male siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, LN-HFHS, n=11-15/group). Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM) at 10 weeks and spatial and object recognition tested at 11 weeks of age. Rats were culled at 13 weeks. Hippocampal mRNA expression was measured using TaqMan(®) Array Micro Fluidic cards (Life Technologies). As expected HFHS diet increased body weight; LN and control rats had similar weights at 13 weeks, energy intake was also similar across groups. LN-Chow rats showed increased anxiety-like behaviour relative to control rats, but this was reversed by HFHS diet. Spatial and object recognition memory were unaltered by LN exposure or consumption of HFHS diet. Hippocampal glucocorticoid receptor (GR) protein was not affected by LN exposure in chow rats, but was increased by 45% in HFHS rats relative to controls. Hippocampal genes involved in plasticity and mood regulation, GSKα and GSKß were affected, with reductions in GSKß under both diet conditions, and reduced GSKα only in LN-HFHS versus Con-HFHS. Interestingly, HFHS diet and LN exposure independently reduced expression of Akt3 mRNA, a key gene involved post-natal brain development. In summary, while an energy rich diet ameliorated anxiety-like behaviour induced by LN exposure, it significantly altered key genes that are essential for hippocampal development.

Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization.

Biofilm-protected microbial infections in skin are a serious health risk that remains to be adequately addressed. The lack of progress in developing effective treatment strategies is largely due to the transport barriers posed by the stratum corneum of the skin and the biofilm. In this work, we report on the use of Ionic Liquids (ILs) for biofilm disruption and enhanced antibiotic delivery across skin layers. We outline the syntheses of ILs, analysis of relevant physicochemical properties, and subsequent neutralization effects on two biofilm-forming pathogens: Pseudomonas aeruginosa and Salmonella enterica. Further, the ILs were also examined for cytotoxicity, skin irritation, delivery of antibiotics through the skin, and treatment of biofilms in a wound model. Of the materials examined, choline-geranate emerged as a multipurpose IL with excellent antimicrobial activity, minimal toxicity to epithelial cells as well as skin, and effective permeation enhancement for drug delivery. Specifically, choline-geranate was comparable with, or more effective than, bleach treatment against established biofilms of S. enterica and P. aeruginosa, respectively. In addition, choline-geranate increased delivery of cefadroxil, an antibiotic, by >16-fold into the deep tissue layers of the skin without inducing skin irritation. The in vivo efficacy of choline-geranate was validated using a biofilm-infected wound model (>95% bacterial death after 2-h treatment). This work establishes the use of ILs for simultaneous enhancement of topical drug delivery and antibiotic activity.