Citations

Study Design Retrospective cohort study Objective Substantial variability in both the measurement and classification of subsidence limits the strength of conclusions that can be drawn from previous studies. The purpose of this study was to precisely characterize patterns of cervical cage subsidence utilizing computed tomography (CT) scans, determine risk factors for cervical cage subsidence, and investigate the impact of subsidence on pseudarthrosis rates. Methods We performed a retrospective review of patients who underwent one- to three-levels of anterior cervical discectomy and fusion (ACDF) utilizing titanium interbodies with anterior plating between the years 2018 and 2020. Subsidence measurements were performed by two independent reviewers on CT scans obtained 6 months postoperatively. Subsidence was then classified as mild if subsidence into the inferior and superior endplate were both ≤2 mm, moderate if the worst subsidence into the inferior or superior endplate was between 2 to 4 mm, or severe if the worst subsidence into the inferior or superior endplate was ≥4 mm. Results A total of 51 patients (100 levels) were included in this study. A total of 48 levels demonstrated mild subsidence (≤2 mm), 38 demonstrated moderate subsidence (2-4 mm), and 14 demonstrated severe subsidence (≥4 mm). Risk factors for severe subsidence included male gender, multilevel constructs, greater mean vertebral height loss, increased cage height, lower Taillard index, and lower screw tip to vertebral body height ratio. Severe subsidence was not associated with an increased rate of pseudarthrosis. Conclusion Following ACDF with titanium cervical cages, subsidence is an anticipated postoperative occurrence and is not associated with an increased risk of pseudarthrosis.

Abstract Aims The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems‐level analysis. Methods Imaging‐based cortical structural maps from a large‐scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell‐type deconvolution, differential expression analysis and cell‐type enrichment analyses were used to identify differences in cell‐type distribution. These differences were followed up in post‐mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell‐type‐specific depletion was used in a murine model of acquired epilepsy. Results We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post‐mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non‐spatial memory test seen in epileptic mice not depleted of microglia. Conclusions These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Hyperstimulation of the cholecystokinin 1 receptor (CCK1R), a G protein–coupled receptor (GPCR), in pancreatic acinar cells is commonly used to induce pancreatitis in rodents. Human pancreatic acinar cells lack CCK1R but express cholinergic receptor muscarinic 3 (M3R), another GPCR. To test whether M3R activation is involved in pancreatitis, a mutant M3R was conditionally expressed in pancreatic acinar cells in mice. This mutant receptor loses responsiveness to its native ligand, acetylcholine, but can be activated by an inert small molecule, clozapine- N -oxide (CNO). Intracellular calcium and amylase were elicited by CNO in pancreatic acinar cells isolated from mutant M3R mice but not WT mice. Similarly, acute pancreatitis (AP) could be induced by a single injection of CNO in the transgenic mice but not WT mice. Compared with the cerulein-induced AP, CNO caused more widespread acinar cell death and inflammation. Furthermore, chronic pancreatitis developed at 4 weeks after 3 episodes of CNO-induced AP. In contrast, in mice with 3 recurrent episodes of cerulein-included AP, pancreas histology was restored in 4 weeks. Furthermore, the M3R antagonist ameliorated the severity of cerulein-induced AP in WT mice. We conclude that M3R activation can cause the pathogenesis of pancreatitis. This model may provide an alternative approach for pancreatitis research.

Objective: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. Background: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. Methods: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014–2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. Results: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. Conclusion: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Background The purpose of this study was to investigate the outcomes of surface replacement arthroplasty (SRA) for noninflammatory arthritis of the metacarpophalangeal (MCP) joint. Methods Records from 20 SRAs performed between 1995 and 2017 in 17 patients with noninflammatory arthritis affecting the MCP joint were retrospectively reviewed. The mean follow up was 6.6 years. Results Three arthroplasties (15%) underwent 4 revision operations. The 2-, 5-, 10-, and 15-year rates of survival from surface replacement implant revision were 90%, 90%, 79%, and 79%, respectively. Major complications occurring in revised joints included arthrodesis (n = 1) and amputation (n = 1). The overall reoperation rate was 35%. The 2-, 5-, 10-, and 15-year rates of overall reoperation-free survival were 75%, 69%, 60%, and 60%, respectively. Conclusions Pain ratings and MCP arc of motion significantly improved following arthroplasty. Metacarpophalangeal SRA for noninflammatory arthritis can improve arc of motion and pain. Revision is uncommon; however, 1 in 3 joints requires reoperation.

As physician burnout and wellness become increasingly recognized as vital themes for the medical community to address, the topic of chronic work-related conditions in surgeons must be further evaluated. While improving ergonomics and occupational health have been long emphasized in the executive and business worlds, particularly in relation to company morale and productivity, information within the surgical community remains relatively scarce. Chronic peripheral nerve compression syndromes, hand osteoarthritis, cervicalgia and back pain, as well as other repetitive musculoskeletal ailments affect many spinal surgeons. The use of ergonomic training programs, an operating microscope or exoscope, powered instruments for pedicle screw placement, pneumatic Kerrison punches and ultrasonic osteotomes, as well as utilizing multiple surgeons or microbreaks for larger cases comprise several methods by which spinal surgeons can potentially improve workspace health. As such, it is worthwhile exploring these areas to potentially improve operating room ergonomics and overall surgeon longevity.

Abstract Context Elevated concentrations of branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes mellitus (T2DM). Their association with cardiovascular disease (CVD) remains uncertain, particularly in youth. Objective We investigated the role of BCAA and aromatic amino acids (AAA) in obesity, their relationships with novel biomarkers of CVD, and response to a physical activity-based lifestyle intervention (PAL-I) in a randomized controlled study in youth with normal weight (NW) and obesity (OB). Methods Age (14-18 years) and Tanner stage (≥IV) matched youth (OB, n = 15 and NW, n = 6) were studied; the 15 participants with OB underwent a 3-month randomized controlled PAL-I. Circulating amino acid profile, glucose, insulin, lipids, adiponectin, retinol binding protein-4, fibrinogen, high-sensitivity C-reactive protein, interleukin-6, and 25-hydroxy vitamin-D, along with body composition, were measured at baseline and after PAL-I. Independent t tests, analysis of covariance, and mixed-effect models were used for analysis of the data. Results Compared with NW, the concentration of various amino acids, including BCAA and AAA, were altered in OB (P < 0.05). BCAA and AAA showed baseline correlations with body composition and novel biomarkers of CVD, particularly inflammatory factors (all P < 0.05). The PAL-I produced only negligible effects (P > 0.05) on BCAA and AAA. Glutamine, glycine, and aspartic acid decreased with PAL-I (all P < 0.05). Conclusion The novel finding of the BCAA–inflammation relationship, along with strong correlations with nontraditional biomarkers of CVD, may raise the prospect of BCAA as a biomarker of CVD and evoke a potential link between obesity, T2DM, and CVD.

Background: Existing data on the epidemiology of shoulder arthroplasty are limited to future projections of incidence. However, the prevalence of shoulder arthroplasty (the number of individuals with a shoulder arthroplasty alive at a certain time and its implications for the burden of revision procedures) remains undetermined for the United States. Hence, the purpose of this study was to estimate the prevalence of shoulder arthroplasty in the United States. Methods: The National Inpatient Sample (NIS) was queried to count all patients who underwent total shoulder arthroplasty (TSA), including both anatomic and reverse TSA, and hemiarthroplasty between 1988 and 2017. The counting method was used to calculate the current prevalence of TSA and hemiarthroplasty using age and sex-specific population and mortality data from the U.S. Census Bureau. Results: In 2017, an estimated 823,361 patients (95% confidence interval [CI], 809,267 to 837,129 patients) were living in the United States with a shoulder replacement. This represents a prevalence of 0.258%, increasing markedly from 1995 (0.031%) and 2005 (0.083%). Female patients had a higher prevalence at 0.294% than male patients at 0.221%. Over 2% of people who were ≥80 years of age in the United States were living with a shoulder replacement. Furthermore, approximately 60% of patients living with a shoulder replacement had undergone the operation between 2013 and 2017. The incidence of revision shoulder arthroplasty is increasing on an annual basis, with 10,290 revision procedures performed in 2017, costing the U.S. health-care system $205 million. Conclusions: The prevalence of shoulder arthroplasty in the United States has markedly increased over time. This trend will likely continue given increasing life expectancies and exponentially increasing shoulder arthroplasty incidence rates. Most patients do not have long-term follow-up, and revision shoulder arthroplasty rates are increasing, a trend that is projected to continue. The data from our study highlight the enormous public health impact of shoulder replacement and shed light on a potentially increasing revision burden.

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131 I or alternative radionuclides, such as 188 Re and 211 At. Over the past two decades, significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery towards promising new applications in disseminated disease, in particular through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination – critically important issues for preclinical development and clinical translation.