The Fragility of Statistical Findings in Cervical Disc Arthroplasty: a Systematic Review of Randomized Controlled Trials.

PURPOSE: This study employs both the fragility index (FI) and fragility quotient (FQ) to assess the level of robustness in the cervical disc arthroplasty (CDA) literature. We hypothesize that dichotomous outcomes involving CDA would exhibit statistical vulnerability. METHODS: A PubMed search was conducted to evaluate dichotomous data for randomized controlled trials (RCTs) in CDA literature from 2000 to 2023. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 1561 articles screened, 111 met the search criteria, with 35 RCTs evaluating CDA included for analysis. Six hundred and ninety-three outcome events with 130 significant (P < 0.05) outcomes and 563 nonsignificant (P ≥ 0.05) outcomes were identified. The overall FI and FQ for all 693 outcomes were 5 (IQR 3-7) and 0.019 (IQR 0.011-0.043). Fragility analysis of statistically significant outcomes and nonsignificant outcomes both revealed an FI of 5. All of the studies reported loss to follow-up (LTF) data where 65.7% (23) did not report or reported an LTF greater or equal to 5. CONCLUSIONS: The literature regarding CDA RCTs lacks statistical robustness and may misrepresent the conclusions with the sole use of the P value. By implementing the FI and FQ along with the P value, we believe the interpretation and contextualization of the clinical data surrounding CDA will be better understood.

Interspecialty Variation in Perioperative Health Care Resource Usage for Carpal Tunnel Release.

BACKGROUND: We investigated whether any interspecialty variation exists, regarding perioperative health care resource usage, in carpal tunnel releases (CTRs). METHODS: The 2010 to 2021 PearlDiver Mariner Database, an all-payer claims database, was queried to identify patients undergoing primary CTRs. Physician specialty IDs were used to identify the specialty of the surgeon-orthopedic versus plastic versus general surgery versus neurosurgery. Multivariate logistic regression analysis was used to identify whether there was any interspecialty variation between the use of health care resources. RESULTS: A total of 908 671 patients undergoing CTRs were included, of which 556 339 (61.2%) were by orthopedic surgeons, 297 047 (32.7%) by plastic surgeons, 44 118 (4.9%) by neurosurgeons, and 11 257 (1.2%) by general surgeons. In comparison with orthopedic surgeons, patients treated by plastic surgeons were less likely to have received opioids, nonsteroidal anti-inflammatory drugs, oral steroids, and preoperative antibiotic prophylaxis but were more likely to have received steroid injections and electrodiagnostic studies (EDSs) preoperatively. Patients treated by neurosurgeons were more likely to have received preoperative opioids, gabapentin, oral steroids, preoperative antibiotic prophylaxis, EDSs, and formal preoperative physical/occupational therapy and less likely to have received steroid injections. Patients treated by general surgeons were less likely to receive oral steroids, steroid injections, EDSs, preoperative formal physical therapy, and preoperative antibiotic prophylaxis, but were more likely to be prescribed gabapentin. CONCLUSIONS: There exists significant variation in perioperative health care resource usage for CTRs between specialties. Understanding reasons behind such variation would be paramount in minimizing differences in how care is practiced for elective hand procedures.

PBX1 as a novel master regulator in cancer: Its regulation, molecular biology, and therapeutic applications.

PBX1 is a critical transcription factor at the top of various cell fate-determining pathways. In cancer, PBX1 stands at the crossroads of multiple oncogenic signaling pathways and mediates responses by recruiting a broad repertoire of downstream targets. Research thus far has corroborated the involvement of PBX1 in cancer proliferation, resisting apoptosis, tumor-associated neoangiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, immune evasion, genome instability, and dysregulating cellular metabolism. Recently, our understanding of the functional regulation of the PBX1 protein has advanced, as increasing evidence has depicted a regulatory network consisting of transcriptional, post-transcriptional, and post-translational levels of control mechanisms. Furthermore, accumulating studies have supported the clinical utilization of PBX1 as a prognostic or therapeutic target in cancer. Preliminary results showed that PBX1 entails vast potential as a targetable master regulator in the treatment of cancer, particularly in those with high-risk features and resistance to other therapeutic strategies. In this review, we will explore the regulation, protein-protein interactions, molecular pathways, clinical application, and future challenges of PBX1.

Priority index for critical Covid-19 identifies clinically actionable targets and drugs.

While genome-wide studies have identified genomic loci in hosts associated with life-threatening Covid-19 (critical Covid-19), the challenge of resolving these loci hinders further identification of clinically actionable targets and drugs. Building upon our previous success, we here present a priority index solution designed to address this challenge, generating the target and drug resource that consists of two indexes: the target index and the drug index. The primary purpose of the target index is to identify clinically actionable targets by prioritising genes associated with Covid-19. We illustrate the validity of the target index by demonstrating its ability to identify pre-existing Covid-19 phase-III drug targets, with the majority of these targets being found at the leading prioritisation (leading targets). These leading targets have their evolutionary origins in Amniota ('four-leg vertebrates') and are predominantly involved in cytokine-cytokine receptor interactions and JAK-STAT signaling. The drug index highlights opportunities for repurposing clinically approved JAK-STAT inhibitors, either individually or in combination. This proposed strategic focus on the JAK-STAT pathway is supported by the active pursuit of therapeutic agents targeting this pathway in ongoing phase-II/III clinical trials for Covid-19.

A Cost-Effectiveness Analysis of Pegcetacoplan for the Treatment of Geographic Atrophy.

PURPOSE: To evaluate the cost-effectiveness of the treatment of geography atrophy (GA) with intravitreal pegcetacoplan and to identify utility-measurement surrogates. DESIGN: Cost analysis based on data from a published study. SUBJECTS: None; based on data from published sham control compared with 2 treatment groups in the index study. METHODS: Costs were based on 2022 Medicare reimbursement data. Specific outcomes were extrapolated from the DERBY and OAKS trials. Assumptions were made for the lifetime analysis based on a theoretical logistic growth model of the atrophy. OUTCOME MEASURES: Cost, cost utility, cost per quality-adjusted life-year, and cost per area of GA (in US$). RESULTS: The costs to treat GA in every month (EM) and every-other-month (EOM) treatment groups over the 2 years as reported were $70 000 and $34 600, respectively. The costs per area of delaying GA for 2 years in all patients were $87 300/mm2 (EM) and $49 200/mm2 (EOM), and in initially extrafoveal patients, $53 900/mm2 (EM) and $32 100/mm2 (EOM). The costs per day of delaying GA for 2 years were $295 (EM) and $170 (EOM); the marginal cost (EM vs. EOM) per retinal pigment epithelium cell saved was $30. The modeled lifetime costs were $350 000 (EM) and $172 000 (EOM), or $309 000/mm2 (EM) and $180 000 (EOM) /mm2. The modeled time to 95% atrophy at 13 years was delayed by 2.5 years (EM) and 2.1 years (EOM). The costs/quality-adjusted life-year gained based on modeled visual loss with 95% atrophy were $706 000 (EM) and $397 000 (EOM). CONCLUSION: Treatment of GA with intravitreal pegcetacoplan EOM was more cost effective than EM. Treatment of extrafoveal lesions yielded greater utility than the treatment of the entire group. As atrophy progression approaches an upper limit, the marginal cost/benefit ratios increase. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating the Educational Value of Cancer Registries - a Systematic Review and Thematic Analysis.

Cancer registries encompass a broad array of functions that underpin cancer control efforts. Despite education being fundamental to improving patient outcomes, little is known regarding the educational value of cancer registries. This review will evaluate the educational value of cancer registries for key stakeholders as reported within published literature and identify opportunities for enhancing their educational value. Four databases (Ovid Medline, Embase, CINAHL and Web of Science) were searched using a predefined search strategy in keeping with the PRISMA statement. Data was extracted and synthesised in narrative format. Themes and frequency of discussion of educational content were explored using thematic content analysis. From 952 titles, ten eligible studies were identified, highlighting six stakeholder groups. Educational outcomes were identified relating to clinicians (6/10), researchers (5/10), patients (4/10), public health organisations (3/10), medical students (1/10) and the public (1/10). Cancer registries were found to educationally benefit key stakeholders despite educational value not being a key focus of any study. Deliberate efforts to harness the educational value of cancer registries should be considered to enable data-driven quality improvement, with the vast amount of data promising ample educational benefit.

Endoscopic Evaluation of PET/CT Abnormalities in the Gastrointestinal Tract: Yield and Approach.

BACKGROUND: Unexpected hypermetabolic activity is often encountered in the gastrointestinal tract when PET/CT is performed for various indications, prompting endoscopic evaluation. Our aim was to characterize the types of lesions seen in segments of the gastrointestinal tract with unexpected PET/CT abnormalities as well as clinically significant lesions seen on endoscopy which did not produce a PET/CT abnormality to guide the endoscopist tasked with evaluating these imaging findings. METHODS: We retrospectively reviewed a database of endoscopies performed at City of Hope Comprehensive Cancer Center between January 1, 2016 and September 30, 2021 for an indication of "abnormal PET." We divided the gastrointestinal tract into segments and defined categories of endoscopic/histologic findings for each segment. We counted the number of segments with an abnormal PET/CT finding and corresponding endoscopic/histologic abnormality as well as the number of segments with an endoscopic/histologic abnormality but normal PET/CT. RESULTS: PET/CT identified 209 segments with hypermetabolic activity, 109 of which had corresponding endoscopic/histologic abnormalities. In the jejunum and ileum, all corresponding lesions were malignant. Seventy-three percent of corresponding lesions in the stomach were H. pylori positive. PET/CT failed to detect 34.7% of clinically significant lesions diagnosed endoscopically, including 1 malignancy in the transverse colon and many inflammatory or low-risk premalignant lesions. CONCLUSION: PET/CT abnormalities seen in the small bowel should be evaluated urgently as nearly all correlates were malignant, while abnormalities in the stomach should prompt workup for H. pylori. Most lesions missed by PET/CT were inflammatory or low-risk premalignant yet clinically significant, confirming the need to inspect the entirety of the upper or lower gastrointestinal tract during endoscopy.

The iliac kickstand screw: anatomic CT analysis of screw trajectory and osseous corridor for screw placement.

INTRODUCTION: The 'kickstand screw-rod' technique has been recently described for correction of coronal malalignment. This technique utilizes powerful 'construct-to-ilium' distraction between a fixed multi-screw thoracic construct and the ilium, facilitated by a novel 'iliac kickstand screw'. The 'iliac kickstand screw' traverses a previously undescribed osseous corridor in the ilium. OBJECTIVE: Using a radiographic CT study, the objective is to describe a large osseous corridor within the ilium to accommodate the novel iliac kickstand screw. METHODS: 50 consecutive patients with pelvic CTs at an academic medical center were queried. Simulated iliac kickstand screw trajectories for the left and right hemipelvis were analyzed with 3D visualization software. Maximal screw lengths and dimensions, and trajectories in the osseous corridor were measured. RESULTS: 50 patients' (31 female, 19 male) pelvic CTs were measured with a total of 100 simulated screws. The mean age was 52.4 years and BMI 28.1 ± 7.9. The average length is 119.7 ± 6.6 mm (range 98.7 - 135.3). The narrowest width (maximum potential screw diameter) is 17.8 ± 2.9 mm (coronal) and 20.8 ± 5.3 mm (sagittal). The starting point to the top of the iliac crest is 66.4 mm lateral to midline, and 15.9° caudal in the sagittal and 6.1° lateral in the coronal planes. CONCLUSIONS: The novel iliac kickstand screw traverses a consistent and large osseous corridor within the ilium. The average simulated screw length is 119.7 mm and maximum potential diameter of 17.8 mm. Starting points relative to the iliac crest are identified.

Financial model for a transitional pain service at a large tertiary academic center in the USA.

Approximately 1 in 10 patients undergoing surgery is considered at high risk for poor pain and opioid-related outcomes due to chronic pain or persistent opioid use prior to surgery, leading to increased hospital lengths of stay, emergency department visits, hospital readmissions, and worse long-term outcomes. Multidisciplinary transitional pain services (TPSs) have been shown to effectively identify and optimize high-risk patients before surgery, leading to a reduction in healthcare utilization. We conducted a series of semistructured interviews, a literature search, and a financial analysis to develop a reproducible business case for establishing a TPS. These interviews involved discussions with clinicians and administrators at Michigan Medicine, as well as leaders of TPS initiatives at peer institutions across the USA and Canada. The aim was to understand possible operational structures and potential sources of revenue and cost savings that needed inclusion in our model. Subsequently, the authors developed a modifiable financial modeling tool, which is freely available for download and adaptable to any healthcare institution. The model suggests that the primary source of cost savings can be attributed to a reduction in length of stay. Furthermore, several operational options exist for incorporating a TPS that performs at breakeven or positive net profit. This tool and these findings are important for informing health systems of operational and financial considerations when implementing a TPS program. Future research should evaluate this financial tool's reproducibility in community health system contexts.

GiftBTE: an efficient deterministic solver for non-gray phonon Boltzmann transport equation.

Advances in nanotechnology have facilitated the exploration of submicron thermal transport. At this scale, Fourier's law is no longer applicable, and the governing equation for thermal transport is the phonon Boltzmann transport equation (BTE). However, the availability of open-source solvers for the phonon BTE is limited, impeding progress in this field. This study introduces an open-source package, GiftBTE, for numerically solving the non-gray phonon BTE. GiftBTE employs deterministic solutions and provides both steady-state and transient solvers. For the steady-state solver, GiftBTE employs the implicit discrete ordinates method (DOM) with second-order spatial accuracy and the synthetic iterative scheme. For the transient solver, GiftBTE employs the explicit DOM with second-order spatial accuracy. This package demonstrates excellent computational efficiency, enabling realistic three-dimensional simulations of devices and materials. By interfacing with first-principles calculations, this solver enables parameter-free computation of submicron thermal transport. The application of GiftBTE includes, but is not limited to, computing the thermal conductivity of nanostructures, predicting temperature rises in transistors, and simulating laser heating processes.

Da Vinci Meets Globus Excelsius GPS: A Totally Robotic Minimally Invasive Anterior and Posterior Lumbar Fusion.

BACKGROUND: Minimally invasive approaches to the spine via anterior and posterior approaches have been increasing in popularity, culminating in the development of robot-assisted spinal fusions. The da Vinci surgical robot has been used for anterior lumbar interbody fusion (ALIF), with promising results. Similarly, multiple spinal robots have been developed to assist placement of posterior pedicle screws. However, no previous cases have reported on using robots for both anterior and posterior fixation in a single surgery. We present a technical note on the first reported case of a totally robotic minimally invasive anterior and posterior lumbar fusion and instrumentation. METHODS: A 65-year-old man with chronic low back pain and left greater than right lower extremity radiculopathy was found to have grade 1 spondylolisthesis at L5/S1 that worsened on standing upright. He underwent ALIF using a da Vinci robotic approach, followed by percutaneous posterior instrumented fusion with the Globus Excelsius GPS robot. RESULTS: The patient did well postoperatively, with improvement of back and leg pain at 3 months follow-up. Radiography confirmed appropriate placement of the interbody cage and pedicle screws. CONCLUSIONS: All-robotic placement of both ALIF and posterior lumbar pedicle fixation may be safe, feasible, and efficacious.

Cancer incidence and outcomes registries in an Australian context: a systematic review.

BACKGROUND: Multiple cancer registries in Australia are used to track the incidence of cancer and the outcomes of their treatment. These registries can be broadly classed into a few types with an increasing number of registries comes a greater potential for collaboration and linkage. This article aims to critically review cancer registry types in Australia and evaluate the Australian Cancer registry landscape to identify these areas. METHODS: A systematic review was performed through MEDLINE, EMBASE and Cochrane Library, updated to September 2022 using a predefined search strategy. Inclusion criteria were those that only analysed Australian and/or New Zealand based cancer registries, appraised the utility of cancer outcomes and/or incidence registries, and explored the utility of linked databases using cancer outcomes and/or incidence registries. The grey literature was searched for all operating cancer registries in Australia. Details of registry infrastructure was extracted for analysis and comparison. RESULTS: Three thousand two hundred and sixteen articles identified from the three databases. Twelve met the inclusion criteria. Twenty-eight registries were identified using the grey literature. Strengths and weaknesses of Cancer Outcome Registries(COR) and Cancer Incidence Registries(CIR) were compared. Data linkage between registries or with other healthcare databases show great benefits in improving evidence for cancer research but are challenging to implement. Both registry types utilize differing modes of administration, influencing their accuracy and completeness. CONCLUSION: Outcome registries provide detailed data but their weakness lies in incomplete data coverage. Incidence registries record a large dataset which contain inaccuracies. Improving coverage of quality outcome registries, and quality assurance of data in incidence registries is required to ensure collection of accurate, meaningful data. Areas for collaboration identified included establishment of defined definitions and outcomes, data linkage between registry types or with healthcare databases, and collaboration in logistical planning to improve clinical utility of cancer registries.

Challenges in Nerve Repair and Reconstruction.

Peripheral nerve injuries may substantially impair a patient's function and quality of life. Despite appropriate treatment, outcomes often remain poor. Direct repair remains the standard of care when repair is possible without excessive tension. For larger nerve defects, nerve autografting is the gold standard. However, a considerable challenge is donor site morbidity. Processed nerve allografts and conduits are other options, but evidence supporting their use is limited to smaller nerves and shorter gaps. Nerve transfer is another technique that has seen increasing popularity. The future of care may include novel biologics and pharmacologic therapy to enhance regeneration.

A New Objective Radiographic Criteria for Diagnosis of Adult Idiopathic Scoliosis: Apical Pedicle Diameter Asymmetry.

OBJECTIVE: We sought to test the hypothesis that a difference of ≥1 mm in pedicle diameter between the convex and concave pedicles at the apex of a lumbar curve is a sensitive and/or specific criteria for adult idiopathic scoliosis (AdIS). METHODS: Thirty-nine operative patients with adult deformity and lumbar major curves were identified. A chart review was performed. Radiographic measurements included lumbar Cobb, curve apex, and Cobb levels involved. Apical pedicle diameter at the concavity and convexity of the curve apex were measured. RESULTS: Among these 39 patients, the average Cobb angle was 48.3 degrees. Curve apex averaged at L1/2 (range L1-L3). The curves spanned 4.7 levels (range 3-7). Twenty-five curves had the apex to the left, while 14 had the apex to the right. The average pedicle diameter at the apex was 6.1 mm. Fourteen patients had apical pedicle diameter asymmetry (APDA) >1 mm. Most (7 of 8, or 87.5%) of the patients with a history of adult idiopathic scoliosis had APDA >1 mm. A minority (7 of 31, 22.5%) of patients without known history of adult idiopathic scoliosis had APDA >1 mm (P < 0.01). CONCLUSIONS: Apical pedicle diameter asymmetry is among the sensitive diagnostic criteria for AdIS and may be useful for differentiating lumbar major AdIS from degenerative lumbar scoliosis. The sensitivity of APDA >1 mm is 87.5%, with specificity of 77.4%. We propose a new, sensitive radiographic criterion for adult idiopathic scoliosis. A difference of ≥1 mm in pedicle diameter between the convex and concave pedicles at that apex of a lumbar curve has a sensitivity of 87.5% and specificity of 77.4% for patient-reported history of adolescent scoliosis. It can be a useful tool as exclusion criteria for studies on AdIS.

Structure-activity relationship study of central pyridine-derived TYK2 JH2 inhibitors: Optimization of the PK profile through C4' and C6 variations.

Efforts directed at improving potency and preparing structurally different TYK2 JH2 inhibitors from the first generation of compounds such as 1a led to the SAR study of new central pyridyl based analogs 2-4. The current SAR study resulted in the identification of 4h as a potent and selective TYK2 JH2 inhibitor with distinct structural differences from 1a. In this manuscript, the in vitro and in vivo profiles of 4h are described. The hWB IC50 of 4h was shown as 41 nM with 94% bioavailability in the mouse PK study.

OpenXGR: a web-server update for genomic summary data interpretation.

How to effectively convert genomic summary data into downstream knowledge discovery represents a major challenge in human genomics research. To address this challenge, we have developed efficient and effective approaches and tools. Extending our previously established software tools, we here introduce OpenXGR (http://www.openxgr.com), a newly designed web server that offers almost real-time enrichment and subnetwork analyses for a user-input list of genes, SNPs or genomic regions. It achieves so through leveraging ontologies, networks, and functional genomic datasets (such as promoter capture Hi-C, e/pQTL and enhancer-gene maps for linking SNPs or genomic regions to candidate genes). Six analysers are provided, each doing specific interpretations tailored to genomic summary data at various levels. Three enrichment analysers are designed to identify ontology terms enriched for input genes, as well as genes linked from input SNPs or genomic regions. Three subnetwork analysers allow users to identify gene subnetworks from input gene-, SNP- or genomic region-level summary data. With a step-by-step user manual, OpenXGR provides a user-friendly and all-in-one platform for interpreting summary data on the human genome, enabling more integrated and effective knowledge discovery.