The impact of enhanced recovery after surgery (ERAS) on opioid consumption and postoperative pain levels in elective spine surgery.

OBJECTIVE: Enhanced Recovery after Surgery (ERAS) protocols were developed to counteract the adverse effects of the surgical stress response, aiming for quicker postoperative recovery. Initially applied in abdominal surgeries, ERAS principles have extended to orthopedic spine surgery, but research in this area is still in its infancy. The current study investigated the impact of ERAS on postoperative pain and opioid consumption in elective spine surgeries. METHODS: A single-center retrospective study of patients undergoing elective spine surgery from May 2019 to July 2020. Patients were categorized into two groups: those enrolled in the ERAS pathway and those adhering to traditional surgical protocols. Data on demographics, comorbidities, length of stay (LOS), surgical procedures, and postoperative outcomes were collected. Postoperative pain was evaluated using the Numerical Rating Scale (NRS), while opioid utilization was quantified in morphine milligram equivalents (MME). NRS and MME were averaged for each patient across all days under observation. Differences in outcomes between groups (ERAS vs. treatment as usual) were tested using the Wilcoxon rank sum test for continuous variables and Pearson's or Fisher's exact tests for categorical variables. RESULTS: The median of patient's mean daily NRS scores for postoperative pain were not statistically significantly different between groups (median = 5.55 (ERAS) and 5.28 (non-ERAS), p=.2). Additionally, the median of patients' mean daily levels of MME were similar between groups (median = 17.24 (ERAS) and 16.44 (non-ERAS), p=.3) ERAS patients experienced notably shorter LOS (median=2 days) than their non-ERAS counterparts (median=3 days, p=.001). The effect of ERAS was moderated by whether the patient had ACDF surgery. ERAS (vs. non-ERAS) patients who had ACDF surgery had 1.64 lower average NRS (p=.006). ERAS (vs. non-ERAS) patients who had a different surgery had 0.72 higher average NRS (p=.02) but had almost half the length of stay, on average (p<.001). CONCLUSIONS: The current study underscores the dynamic nature of ERAS protocols within the realm of spine surgery. While ERAS demonstrates advantages such as reduced LOS and improved patient-reported outcomes, it requires careful implementation and customization to address the specific demands of each surgical discipline. The potential to expedite recovery, optimize resource utilization, and enhance patient satisfaction cannot be overstated. However, the fine balance between achieving these benefits and ensuring comprehensive patient care, especially in the context of postoperative pain management, must be maintained. As ERAS continues to evolve and find its place in diverse surgical domains, it is crucial for healthcare providers to remain attentive to patient needs, adapting ERAS protocols to suit individual patient populations and surgical contexts.

Conditional deletion of Zeb1 in Csf1r+ cells reduces inflammatory response of the cornea to alkali burn.

ZEB1 is an essential factor in embryonic development. In adults, it is often highly expressed in malignant tumors with low expression in normal tissues. The major biological function of ZEB1 in developing embryos and progressing cancers is to transdifferentiate cells from an epithelial to mesenchymal phenotype; but what roles ZEB1 plays in normal adult tissues are largely unknown. We previously reported that the reduction of Zeb1 in monoallelic global knockout (Zeb1+/-) mice reduced corneal inflammation-associated neovascularization following alkali burn. To uncover the cellular mechanism underlying the Zeb1 regulation of corneal inflammation, we functionally deleted Zeb1 alleles in Csf1r+ myeloid cells using a conditional knockout (cKO) strategy and found that Zeb1 cKO reduced leukocytes in the cornea after alkali burn. The reduction of immune cells was due to their increased apoptotic rate and linked to a Zeb1-downregulated apoptotic pathway. We conclude that Zeb1 facilitates corneal inflammatory response by maintaining Csf1r+ cell viability.

Integration of Chronological Age Does Not Improve the Performance of a Mixed-Effect Model Using Comorbidity Burden and Frailty to Predict 90-Day Readmission After Surgery for Degenerative Scoliosis.

OBJECTIVE: We evaluated the contributions of chronological age, comorbidity burden, and/or frailty in predicting 90-day readmission in patients undergoing degenerative scoliosis surgery. METHODS: Patients were identified through the Healthcare Cost and Utilization Project Nationwide Readmissions Database. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. Comorbidity was assessed using the Elixhauser Comorbidity Index (ECI). Generalized linear mixed-effects models were created to predict readmission using age, frailty, and/or ECI. Area under the curve (AUC) was compared using DeLong's test. RESULTS: A total of 8104 patients were identified. Readmission rate was 9.8%, with infection representing the most common cause (3.5%). Our first model utilized chronological age, ECI, and/or frailty as primary predictors. The combination of ECI + frailty + age performed best, but the inclusion of chronological age did not significantly improve performance compared to ECI + frailty alone (AUC 0.603 vs. 0.599, P = 0.290). A second model using only chronological age and frailty as primary predictors performed better, however the inclusion of chronological age worsened performance when compared to frailty alone (AUC 0.747 vs. 0.743, P = 0.043). CONCLUSIONS: These data support frailty as a predictor of 90-day readmission within a nationally representative sample. Frailty alone performed better than combinations of ECI and age. Interestingly, the integration of chronological age did not dramatically improve the model's performance. Limitations include the use of a national registry and a single frailty index. This provides impetus to explore biological age, rather than chronological age, as a potential tool for surgical risk assessment.

Primary central nervous system post-transplantation lymphoproliferative disorder: A case report and systematic review of imaging findings.

Primary central nervous system post-transplant lymphoproliferative disease (PCNS-PTLD) is a rare subset of post-transplant lymphoproliferative disorder (PTLD) isolated to the CNS without nodal or extra-nodal organ involvement [1,2]. PCNS-PTLD occurs primarily in patients following either solid organ transplants or hematopoietic stem cell transplants and tends to be monomorphic DLBCL. The development of PCNS-PTLD is commonly associated with EBV infection [3]. Many intracranial pathologies can resemble the imaging appearance of PCNS-PTLD, including primary CNS lymphoma, glial tumors, metastatic disease, and intracranial abscesses. The purpose of this systematic review is to identify the most common imaging characteristics of PCNS-PTLD. Our review included 97 sources that describe the imaging appearance of PCNS-PTLD. Based on our review, PCNS-PTLD lesions are typically multifocal, ring-enhancing and diffusion-restricting. PCNS-PTLD lesions typically demonstrate focal FDG avidity. Despite advancement in medical imaging, PCNS-PTLD remains a diagnostic challenge due to its rare incidence. Limited data is available on advanced imaging with regards to PTLD, but techniques including DCE-MRI and fMRI demonstrate promising results that may help further delineate PCNS-PTLD.

Top 25 Most Cited Articles on Intraoperative Computer Tomography-Guided Navigation in Spine Surgery.

BACKGROUND: In recent years, the use of intraoperative computer tomography-guided (CT-guided) navigation has gained significant popularity among health care providers who perform minimally invasive spine surgery. This review aims to identify and analyze trends in the literature related to the widespread adoption of CT-guided navigation in spine surgery, emphasizing the shift from conventional fluoroscopy-based techniques to CT-guided navigation. METHODS: Articles pertaining to this study were identified via a database review and were hierarchically organized based on the number of citations. An "advanced document search" was performed on September 28th, 2022, utilizing Boolean search operator terms. The 25 most referenced articles were combined into a primary list after sorting results in descending order based on the total number of citations. RESULTS: The "Top 25" list for intraoperative CT-guided navigation in spine surgery cumulatively received a total of 2742 citations, with an average of 12 new citations annually. The number of citations ranged from 246 for the most cited article to 60 for the 25th most cited article. The most cited article was a paper by Siewerdsen et al., with 246 total citations, averaging 15 new citations per year. CONCLUSIONS: Intraoperative CT-guided navigation is 1 of many technological advances that is used to increase surgical accuracy, and it has become an increasingly popular alternative to conventional fluoroscopy-based techniques. Given the increasing adoption of intraoperative CT-guided navigation in spine surgery, this review provides impactful evidence for its utility in spine surgery.

A Case Presentation of a Rare Pelvic Interdigitating Dendritic Cell Sarcoma.

Sarcoma is a rare type of cancer that arises from connective tissue. Interdigitating dendritic cell sarcoma (IDCS) is a rare neoplasm of dendritic cell origin. IDCS arises from interdigitating dendritic cells found in the T-cell regions of secondary lymphoid tissues. Due to the rare nature of IDCS diagnosis, management can be difficult. Often, the diagnosis is delayed due to a lack of symptoms and signs. Here, we describe a case of a 34-year-old female patient who presented with an incidental finding of a left sidewall pelvic mass later to be confirmed on biopsy as an IDCS.

Simulated outcomes for durotomy repair in minimally invasive spine surgery.

Minimally invasive spine surgery (MISS) is increasingly performed using endoscopic and microscopic visualization, and the captured video can be used for surgical education and development of predictive artificial intelligence (AI) models. Video datasets depicting adverse event management are also valuable, as predictive models not exposed to adverse events may exhibit poor performance when these occur. Given that no dedicated spine surgery video datasets for AI model development are publicly available, we introduce Simulated Outcomes for Durotomy Repair in Minimally Invasive Spine Surgery (SOSpine). A validated MISS cadaveric dural repair simulator was used to educate neurosurgery residents, and surgical microscope video recordings were paired with outcome data. Objects including durotomy, needle, grasper, needle driver, and nerve hook were then annotated. Altogether, SOSpine contains 15,698 frames with 53,238 annotations and associated durotomy repair outcomes. For validation, an AI model was fine-tuned on SOSpine video and detected surgical instruments with a mean average precision of 0.77. In summary, SOSpine depicts spine surgeons managing a common complication, providing opportunities to develop surgical AI models.

Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials.

INTRODUCTION: Immune-mediated inflammatory diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on patients and their quality of life. Upadacitinib is an orally administered, selective, and reversible Janus kinase inhibitor indicated for seven conditions, but data on its safety versus other active treatments are limited. A systematic literature review of indirect and direct treatment comparisons of randomized controlled trials (RCTs) was conducted to assess the safety profile of upadacitinib. METHODS: MEDLINE, Embase, and Cochrane Library databases were searched for indirect and direct treatment comparisons of RCTs that (1) included licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) reported any adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, major adverse cardiovascular event, venous thromboembolism, malignancies, infections or serious infections, and death; and (4) were published between January 2018 and August 2022. RESULTS: A total of 25 studies were eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were commonly studied. RA was the most studied condition, followed by AD and UC. Most studies (16/25, 64%) reported no statistically significant difference in the studied safety outcomes between upadacitinib and other active treatments (e.g., tumor necrosis factor blockers, interleukin receptor antagonists, integrin receptor antagonists, T cell co-stimulation modulator), or placebo (placebo ± methotrexate or topical corticosteroids). Other studies (9/25, 36%) reported mixed results of no statistically significant difference and either statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib. CONCLUSION: Most studies suggested that upadacitinib has no statistically significant difference in the studied safety outcomes compared to active treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies reported higher rates, but findings were inconsistent with limited interpretation.

Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: Analysis of the 3-Year Phase 3 Rising Up Study.

INTRODUCTION: Upadacitinib is an oral Janus kinase inhibitor approved in multiple countries for moderate-to-severe atopic dermatitis (AD). Here we present long-term data for up to 3 years of continuous upadacitinib treatment in Japanese patients with AD. METHODS: Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upadacitinib in patients with moderate-to-severe AD. Patients aged 12-75 years (weight ≥ 40 kg if < 18 years) were randomized 1:1:1 to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo through week 16 (all in combination with topical corticosteroids). At week 16, patients who received placebo were rerandomized 1:1 to upadacitinib 15 mg or 30 mg; topical corticosteroids were optional per investigator discretion from weeks 16-160. Safety was assessed by monitoring adverse events (AEs). Efficacy assessments included patients who achieved ≥ 75%/≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), clear/almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), or a ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (WP-NRS). RESULTS: Of 272 patients enrolled, 230 completed the study. Through week 160, the long-term incidence rate of overall AEs was numerically higher with upadacitinib 30 mg than 15 mg; rates of serious AEs, AEs considered possibly related to study drug, AEs leading to discontinuation, and AEs of special interest were generally low and similar between dose groups. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were generally greater with upadacitinib 30 mg than 15 mg and maintained through week 160 with either dose. CONCLUSION: For up to 3 years of continuous treatment, upadacitinib was well tolerated in Japanese patients, with a similar safety profile to that of short-term studies and durable long-term response rates for skin clearance and itch improvement. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03661138.

Quantifying plasma dacarbazine levels in advanced melanoma patients: a liquid chromatography-tandem mass spectrometry performance analysis.

The aim of this study was to develop a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying dacarbazine levels in the plasma of advanced melanoma patients, followed by an assessment of its analytical capabilities. The research encompassed the design of a high-performance liquid chromatography (HPLC) system, with the quantitative analysis performed using the multiple reaction monitoring (MRM) techniques and specific ion transition: 181.0 > 152.5 for dacarbazine and 187.1 > 158.6 for the internal standard (IS), dacarbazine-D6. The validation of the method involved an evaluation of parameters including linearity, detection limit, precision, and accuracy. Notably, the linear range extended from 10 to 1,000 µg/L for dacarbazine, and the method exhibited a detection limit of 10 µg/L. The method's precision, indicated by within-run and between-run coefficients of variation (CV), both being ≤4.2% and ≤8.3%, respectively. Furthermore, the accuracy of measurements, ranging from 86.1% to 99.4%, underscored the method's reliability. In clinical application, the dacarbazine levels of healthy control (n = 20) were 0.6 ± 0.02 µg/L; 770.9 ± 203.2 µg/mL in early-stage-melanoma patients (n = 22), and 588.7 ± 153.2 µg/mL in advanced melanoma patients (n = 25). The results serve as clinical evidence showing that long-term dacarbazine treatment affects the metabolism of dacarbazine.