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Objective: Pedicle screw fixation is a commonly utilized adjunct for lumbar interbody fusion, yet risks include screw malposition, pullout, loosening, neurovascular injury, and stress transfers leading to adjacent segment degeneration. This report describes the preclinical and initial clinical results of a minimally invasive, metal-free cortico-pedicular fixation device used for supplemental posterior fixation in lumbar interbody fusion., Methods: Safety of arcuate tunnel creation was evaluated in cadaveric lumbar (L1-S1) specimens. A finite element analysis study evaluated clinical stability of the device to pedicular screw-rod fixation at L4-L5. Preliminary clinical results were assessed by analysis of Manufacturer and User Facility Device Experience database complications, and 6-month outcomes in 13 patients treated with the device., Results: Among 35 curved drill holes in 5 lumbar specimens, no breaches of the anterior cortex were identified. The mean minimum distance from the anterior surface of the hole to the spinal canal ranged from 5.1 mm at L1-L2 to 9.8 mm at L5-S1. In the finite element analysis study, the polyetheretherketone strap provided comparable clinical stability and reduced anterior stress shielding compared to the conventional screw-rod construct. The Manufacturer and User Facility Device Experience database identified 1 device fracture with no clinical sequelae among 227 procedures. Initial clinical experience showed a 53% decrease in pain severity (P = 0.009), a 50% decrease in Oswestry Disability Index (P < 0.001), and no device-related complications., Conclusions: Cortico-pedicular fixation is a safe and reproducible procedure that may address limitations of pedicle screw fixation. Longer term clinical data in large clinical studies are recommended to confirm these promising early results., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A highly convergent total synthesis of (-)-bastimolide A (1), a polyhydroxy antimalarial macrolide, has been achieved via a longest linear sequence of twenty steps from commercially available glycidyl ethers. Type I Anion Relay Chemistry (ARC) coupling tactics enable rapid construction of the molecule's 1,5-polylol backbone. A late-stage B-alkyl Suzuki-Miyaura union and an Evans-modified Mukaiyama macrolactonization generate the forty-membered Z-α,β-unsaturated macrocyclic lactone., (© 2022 Wiley-VCH GmbH.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity., Competing Interests: The authors have declared that no competing interests exist.

Longeracemine, a member of the Daphniphyllum family of alkaloids contains a novel carbon framework featuring a highly functionalized 2-azabicyclo[2.2.1]heptane core as part of an overall 5/6/5/5/6/5 skeleton. A synthetic intermediate containing the core of longeracemine has been efficiently prepared by employing a stereoselective SmI 2 -mediated cascade reaction to advance a 7-azabicyclo[2.2.1]heptadiene to a 2-azabicyclo[2.2.1]heptene that is functionally poised for conversion to the natural product., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The development of a concise total synthesis of (±)-phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen-oxygen (N-O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early-stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N-O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Prader-Willi syndrome (PWS) is a complex genetic condition, affecting between 1:10,000 and 1:30,000. The prevalence of hip dysplasia in children with PWS is reportedly between 8% and 30%, but the long-term consequences of residual hip dysplasia remain largely unknown in this population. The purpose of this study was to comparatively estimate the number of total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures performed on adults with and without PWS, using a national hospital discharge database, in an effort to elucidate long-term outcomes and guide clinicians treating orthopaedic concerns in younger individuals with PWS., Methods: The National Inpatient Sample of the Healthcare Cost and Utilization Project is the largest all-payer inpatient care database, containing annual data from >7 million hospital stays; sampling weights and stratification variables are provided for producing estimates of >35 million hospitalizations nationwide. THA and TKA procedures were identified, then stratified by whether or not the patient had a diagnosis of PWS. The ages of the 2 groups and sex mix were compared, as was the length of stay for the procedure, and discharge status., Results: From 2004 to 2014, 9.4 million patients nationwide, by weighted estimate, underwent THA (3.1 million) or TKA (6.3 million). Sixty-five patients were identified as having the diagnosis of PWS (39 with THA, 26 with TKA); 7 patients per million having hip or knee arthroplasties had PWS. Sixty-eight percent of those with PWS were younger than 50 years, compared with only 7% of those without PWS (P<0.001). The female:male prevalence was 47:53 for patients with PWS and 60:40 for the total group. The mean length of stay was similar, but patients with PWS were more likely to be transferred to another facility after surgery (77% vs. 36%; P=0.008)., Conclusions: Hip dysplasia prevalence is higher in persons with PWS, but the rate of late treatment with THA is much lower than in the general population. We recommend only active observation for stable and improving hips in young children with PWS, as the consequences of overtreatment can be serious, including further delaying their neuromuscular development, and exposure to possibly unnecessary perioperative risks., Level of Evidence: Nation-wide database analysis, Level IV.

The total syntheses of (-)-herquline B (2) and a heretofore-unrecognized congener, (+)-herquline C (3), are described. The syntheses require 14 and 13 steps, respectively, and feature a key oxazoline reduction that sets the stage for piperazine construction.

Object: Venous thromboembolism (VTE) represents a significant complication after spine surgery, with reported rates as high as 2%-4%. Published institutional practices for VTE prophylaxis are highly variable. In 2008, the authors implemented a departmental protocol for early VTE prophylaxis consisting of combined compressive devices and subcutaneous heparin initiated either preoperatively or on the same day of surgery. In this study, the authors compared the incidence of VTE in spine surgery patients before and after implementing this protocol., Methods: An institutional review board-approved retrospective review of outcomes in patients undergoing spine surgery 2 years before protocol implementation (representing the preprotocol group) and of outcomes in patients treated 2 years thereafter (the postprotocol group) was conducted. Inclusion criteria were that patients were 18 years or older and had been admitted for 1 or more days. Before 2008 (preprotocol), VTE prophylaxis was variable and provider dependent without any uniform protocol. Since 2008 (postprotocol), a new VTE-prophylaxis protocol was administered, starting either preoperatively or on the same day of surgery and continuing throughout hospitalization. The new protocol consisted of 5000 U heparin administered subcutaneously 3 times daily, except in patients older than 75 years or weighing less than 50 kg, who received this dose twice daily. All patients also received sequential compression devices (SCDs). The incidence of VTE in the 2 protocol phases was identified by codes of the International Classification of Diseases, Ninth Revision (ICD-9) codes for deep vein thrombosis (DVT) and pulmonary embolus (PE). Bleeding complications arising from anticoagulation treatments were evaluated by the Current Procedural Terminology (CPT) code for postoperative epidural hematoma (EDH) requiring evacuation., Results: In total, 941 patients in the preprotocol group met the inclusion criteria: 25 had DVT (2.7%), 6 had PE (0.6%), and 6 had postoperative EDH (0.6%). In the postprotocol group, 992 patients met the criteria: 10 had DVT (1.0%), 5 had PE (0.5%), and 4 had postoperative EDH (0.4%). This reduction in DVT after the protocol's implementation was statistically significant (p = 0.009). Despite early aggressive prophylaxis, the incidence of postoperative EDH did not increase and compared favorably to the published literature., Conclusions: At a high-volume tertiary center, an aggressive protocol for early VTE prophylaxis after spine surgery decreases VTE incidence without increasing morbidity.

Objective: To identify deficiencies leading to readmissions to the University of Florida Neurosurgery Service by using the Institute for Healthcare Improvement STate Action on Avoidable Rehospitalizations Readmissions diagnostic tool and to report the opinions of patients, their families, and health care providers., Methods: A retrospective review of hospital admission and discharge data was conducted. All patients who met eligibility criteria and who were discharged from the neurosurgery service between January 1 and March 31, 2012, and readmitted within 30 days after discharge (n=74; 66 patients; 7 multiple readmissions) were included. A chart review revealed potential precipitating factors. Health care providers, patients, and family members were also interviewed. Median values and frequencies were used to summarize the data., Results: The 30-day readmission rate on the neurosurgery service was 14%. Problems associated with wound care accounted for 24% of readmissions, neurologic conditions accounted for 50%, and other medical conditions accounted for 26%. Patients and providers agreed on the medical diagnoses resulting in readmission, but providers also often named "patient noncompliance" as a factor leading to readmission, whereas patients often thought they either were "sent home too early" or had a "general decline with no improvement.", Conclusions: Systematic patterns and common themes associated with patient readmissions were identified for a neurosurgical service. These findings are now being used to implement changes in discharge planning., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ossification of the posterior longitudinal ligament (OPLL) is a disease process characterized by progressive growth and calcification resulting in spinal canal compromise and serious neurological sequelae in advanced cases. Historically, OPLL has most commonly been treated with posterior surgical decompression. Although this procedure indirectly decompresses the spinal cord, it does not address the offending pathological entity, and further growth of the lesion may result in delayed neurological deterioration. This fact is particularly relevant because a number of long-term studies have revealed both longitudinal and transverse disease progression in individuals treated both surgically and conservatively. Despite these high rates of radiographically documented progression, however, the rate of neurological decline in patients undergoing posterior surgery with laminoplasty is low. In this article, the authors review the pathophysiology of OPLL, evidence of disease progression, and outcome data addressing conservative and surgical treatments.

Background: Radiographic response of brain metastasis to stereotactic radiosurgery (SRS) over time has not been well characterized. Being able to predict SRS-induced changes in tumor size over time may allow improved counseling of patients and potentially earlier recognition of poor response to SRS., Objective: To quantify the rate of change in size of metastatic brain tumors after treatment with a linear accelerator (LINAC) SRS., Methods: We performed a retrospective analysis of patients with single metastatic brain tumors treated with LINAC SRS at the University of Florida between 1992 and 2009 who had at least one MRI after treatment. A total of 218 patients with 406 follow-up MRI scans were included in the study. Tumor area was calculated by measuring the largest tumor area on axial imaging and using the equation for area of an ellipse. Primary outcome was percent change in tumor size. The contribution of several factors including gender, primary tumor histology, synchronous or asynchronous presentation, prior treatment, primary tumor control, and SRS dose were examined using multivariate analysis., Results: Mean patient age was 58.3 years (range 4-86), and 48.6% of patients were female. Sixty-three percent of patients had primary tumor control and 70.6% had asynchronous presentation of their brain metastases. SRS peripheral dose range was 1,000-2,250 cGy with a median of 1,750 cGy. The mean percent size change was -22.6% with a mean rate of change of -7.0% per month. The median percent change was -49.7% with a median rate of change of -8.8% per month. The median follow-up was 4.8 months (range 0.3-52.5). Female gender and melanoma histology were found to be significant predictors of an increase in tumor size. Lack of previous surgical resection was a significant predictor of a decrease in tumor size after SRS. Other factors tested with multivariate analysis, including age, synchronicity of presentation, dose, dose volume, Karnofsky performance score, and primary tumor control, were not significant in predicting tumor size change after SRS., Conclusion: In this study, brain metastases decreased in size by a median of 50% for a median follow-up of 4.8 months after SRS. The overall rate of decrease was 9% per month after treatment with SRS. Melanoma histology was a predictor of poor tumor control., (Copyright © 2012 S. Karger AG, Basel.)

Background/aims: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is responsible for multiple different signaling processes including positive effects on bone formation and fusion. In 2002, rhBMP-2 was approved for use in anterior lumbar spinal fusion by the Food and Drug Administration. Since that time, rhBMP-2 use for spinal fusion has become widespread. The use of rh-BMP2 for pediatric spinal fusion, however, has not been widely reported. We report the experience of the use of rhBMP-2 for pediatric spinal fusion at the University of Florida., Methods: Data on patients under the age of 18 years who underwent spinal fusion with rhBMP-2 as an adjunct were retrospectively collected. Of these, 17 met the inclusion criteria and were reviewed. Two patients did not have adequate postoperative imaging. Fifteen patients were included in the final review., Results: All 15 patients showed osseous fusion. Complications included one CSF leak and one wound infection, one misplaced screw requiring revision, and one case of adjacent segment kyphosis requiring extension of the original construct., Conclusion: rhBMP-2 is a successful adjunct for fusion in pediatric patients. Many of these patients had congenital defects that historically decrease fusion rates. rhBMP-2 appears safe and has an associated high rate of osseous fusion., (Copyright © 2012 S. Karger AG, Basel.)

Allergic triggers remain vitally important for a large proportion of asthmatics. Increasing evidence indicates that allergic sensitivity may not only cause ongoing asthmatic symptoms with bronchial hyperreactivity and airway inflammation but may also serve as an inducer of the asthmatic condition. Patients with a history and clinical setting suggestive of allergic sensitivity should be evaluated carefully. Whenever possible, allergen avoidance should be encouraged strongly in allergen-sensitive patients with a strong emphasis on patient education. In those patients who continue to be symptomatic with good avoidance measures and appropriate pharmacotherapy, allergy immunotherapy should be considered as an additional treatment measure.