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Background Context: Robotic spine surgery, utilizing 3D imaging and robotic arms, has been shown to improve the accuracy of pedicle screw placement compared to conventional methods, although its superiority remains under debate. There are few studies evaluating the accuracy of 3D navigated versus robotic-guided screw placement across lumbar levels, addressing anatomical challenges to refine surgical strategies and patient safety., Purpose: This study aims to investigate the pedicle screw placement accuracy between 3D navigation and robotic arm-guided systems across distinct lumbar levels., Study Design: A retrospective review of a prospectively collected registry., Patient Sample: Patients undergoing fusion surgery with pedicle screw placement in the prone position, using either via 3D image navigation only or robotic arm guidance., Outcome Measure: Radiographical screw accuracy was assessed by the postoperative computed tomography (CT) according to the Gertzbein-Robbins classification, particularly focused on accuracy at different lumbar levels., Methods: Accuracy of screw placement in the 3D navigation (Nav group) and robotic arm guidance (Robo group) was compared using Chi-squared test/Fisher's exact test with effect size measured by Cramer's V, both overall and at each specific lumbosacral spinal level., Results: A total of 321 patients were included (Nav, 157; Robo, 189) and evaluated 1210 screws (Nav, 651; Robo 559). The Robo group demonstrated significantly higher overall accuracy (98.6 vs 93.9%; p<.001, V=0.25). This difference of no breach screw rate was signified the most at the L3 level (No breach screw: Robo 91.3 vs 57.8%, p<.001, V=0.35) followed by L4 (89.6 vs 64.7%, p<.001, V=0.28), and L5 (92.0 vs 74.5%, p<.001, V=0.22). However, screw accuracy at S1 was not significant between the groups (81.1 vs 72.0%, V=0.10)., Conclusion: This study highlights the enhanced accuracy of robotic arm-guided systems compared to 3D navigation for pedicle screw placement in lumbar fusion surgeries, especially at the L3, L4, and L5 levels. However, at the S1 level, both systems exhibit similar effectiveness, underscoring the importance of understanding each system's specific advantages for optimization of surgical complications., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024. Published by Elsevier Inc.)

Study Design: Retrospective review of a prospectively collected multisurgeon registry., Objective: To evaluate the outcomes of minimally invasive (MI) decompression in patients with severe degenerative scoliosis (DS) and identify factors associated with poorer outcomes., Summary of Background Context: MI decompression has gained widespread acceptance as a treatment option for patients with lumbar canal stenosis and DS. However, there is a lack of research regarding the clinical outcomes and the impact of MI decompression location in patients with severe DS exhibiting a Cobb angle exceeding 20°., Materials and Methods: Patients who underwent MI decompression alone were included and categorized into the DS or control groups based on Cobb angle (>20°). Decompression location was labeled as "scoliosis-related" when the decompression levels were across or between end vertebrae and "outside" when the operative levels did not include the end vertebrae. The outcomes, including the Oswestry Disability Index (ODI), were compared between the propensity score-matched groups for improvement and minimal clinical importance difference (MCID) achievement at ≥1 year postoperatively. Multivariable regression analysis was conducted to identify factors contributing to the nonachievement of MCID in ODI of the DS group at the ≥1-year time point., Results: A total of 253 patients (41 DS) were included in the study. Following matching for age, sex, osteoporosis status, psoas muscle area, and preoperative ODI, the DS groups exhibited a significantly lower rate of MCID achievement in ODI (DS: 45.5% vs. control 69.0%, P =0.047). The "scoliosis-related" decompression (odds ratio: 9.9, P =0.028) was an independent factor of nonachievement of MCID in ODI within the DS group., Conclusions: In patients with a Cobb angle >20°, lumbar decompression surgery, even in the MI approach, may result in limited improvement of disability and physical function. Caution should be exercised when determining a surgical plan, especially when decompression involves the level between or across the end vertebrae., Level of Evidence: 3., Competing Interests: S.A.Q. has the following disclosures: AMOpportunities: Other financial or material support; Annals of Translational Medicine: Editorial or governing board; Association of Bone and Joint Surgeons: Board or committee member; Cervical Spine Research Society: Board or committee member; Contemporary Spine Surgery: Editorial or governing board; Globus Medical: IP royalties; Paid consultant; Paid presenter or speaker; Hospital Special Surgery Journal: Editorial or governing board; HS2, LLC: Stock or stock Options; International Society for the Advancement of Spine Surgery (ISASS) - Program Committee member: Board or committee member; Lifelink.com: Other financial or material support; Lumbar Spine Research Society: Board or committee member; Minimally Invasive Spine Study Group: Board or committee member; North American Spine Society: Board or committee member; Simplify Medical Inc.: Other financial or material support; Society of Minimally Invasive Spine Surgery (SMISS) - Program Committee member: Board or committee member; Spinal Simplicity: Other financial or material support; SpineGuard Inc.: Paid consultant; Stryker: IP royalties; Paid consultant; Surgalign: Paid consultant; Tissue Differentiation Intelligence: Stock or stock Options; Viseon Inc.: Paid consultant; Research support. S.I. has the following disclosures: Globus Medical: Paid presenter or speaker; Stryker: Paid presenter or speaker; Vertebral Columns/International Society for the Advancement of Spine Surgery (ISASS): Editorial or governing board. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The consumer availability and automated response functions of chat generator pretrained transformer (ChatGPT-4), a large language model, poise this application to be utilized for patient health queries and may have a role in serving as an adjunct to minimize administrative and clinical burden., Purpose: To evaluate the ability of ChatGPT-4 to respond to patient inquiries concerning ulnar collateral ligament (UCL) injuries and compare these results with the performance of Google., Study Design: Cross-sectional study., Methods: Google Web Search was used as a benchmark, as it is the most widely used search engine worldwide and the only search engine that generates frequently asked questions (FAQs) when prompted with a query, allowing comparisons through a systematic approach. The query "ulnar collateral ligament reconstruction" was entered into Google, and the top 10 FAQs, answers, and their sources were recorded. ChatGPT-4 was prompted to perform a Google search of FAQs with the same query and to record the sources of answers for comparison. This process was again replicated to obtain 10 new questions requiring numeric instead of open-ended responses. Finally, responses were graded independently for clinical accuracy (grade 0 = inaccurate, grade 1 = somewhat accurate, grade 2 = accurate) by 2 fellowship-trained sports medicine surgeons (D.W.A, J.S.D.) blinded to the search engine and answer source., Results: ChatGPT-4 used a greater proportion of academic sources than Google to provide answers to the top 10 FAQs, although this was not statistically significant (90% vs 50%; P = .14). In terms of question overlap, 40% of the most common questions on Google and ChatGPT-4 were the same. When comparing FAQs with numeric responses, 20% of answers were completely overlapping, 30% demonstrated partial overlap, and the remaining 50% did not demonstrate any overlap. All sources used by ChatGPT-4 to answer these FAQs were academic, while only 20% of sources used by Google were academic ( P = .0007). The remaining Google sources included social media (40%), medical practices (20%), single-surgeon websites (10%), and commercial websites (10%). The mean (± standard deviation) accuracy for answers given by ChatGPT-4 was significantly greater compared with Google for the top 10 FAQs (1.9 ± 0.2 vs 1.2 ± 0.6; P = .001) and top 10 questions with numeric answers (1.8 ± 0.4 vs 1 ± 0.8; P = .013)., Conclusion: ChatGPT-4 is capable of providing responses with clinically relevant content concerning UCL injuries and reconstruction. ChatGPT-4 utilized a greater proportion of academic websites to provide responses to FAQs representative of patient inquiries compared with Google Web Search and provided significantly more accurate answers. Moving forward, ChatGPT has the potential to be used as a clinical adjunct when answering queries about UCL injuries and reconstruction, but further validation is warranted before integrated or autonomous use in clinical settings., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.S.D. has received consulting fees from Arthrex and Trice Medical; royalties or license payments from Linvatec; nonconsulting fees from Arthrex; education payments from Gotham Surgical Solutions & Devices; and hospitality payments from Horizon Pharma. D.W.A. has received royalties or license payments from Stryker and hospitality payments from Arthrex. R.J.W. has received royalties or license payments from Arthrex; acquisitions from Smith+Nephew; nonconsulting fees from Arthrex; consulting fees from Arthrex; and hospitality payments from Joint Restoration Foundation. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Purpose: To assess the ability of ChatGPT-4, an automated Chatbot powered by artificial intelligence, to answer common patient questions concerning the Latarjet procedure for patients with anterior shoulder instability and compare this performance with Google Search Engine., Methods: Using previously validated methods, a Google search was first performed using the query "Latarjet." Subsequently, the top 10 frequently asked questions (FAQs) and associated sources were extracted. ChatGPT-4 was then prompted to provide the top 10 FAQs and answers concerning the procedure. This process was repeated to identify additional FAQs requiring discrete-numeric answers to allow for a comparison between ChatGPT-4 and Google. Discrete, numeric answers were subsequently assessed for accuracy on the basis of the clinical judgment of 2 fellowship-trained sports medicine surgeons who were blinded to search platform., Results: Mean (± standard deviation) accuracy to numeric-based answers was 2.9 ± 0.9 for ChatGPT-4 versus 2.5 ± 1.4 for Google (P = .65). ChatGPT-4 derived information for answers only from academic sources, which was significantly different from Google Search Engine (P = .003), which used only 30% academic sources and websites from individual surgeons (50%) and larger medical practices (20%). For general FAQs, 40% of FAQs were found to be identical when comparing ChatGPT-4 and Google Search Engine. In terms of sources used to answer these questions, ChatGPT-4 again used 100% academic resources, whereas Google Search Engine used 60% academic resources, 20% surgeon personal websites, and 20% medical practices (P = .087)., Conclusions: ChatGPT-4 demonstrated the ability to provide accurate and reliable information about the Latarjet procedure in response to patient queries, using multiple academic sources in all cases. This was in contrast to Google Search Engine, which more frequently used single-surgeon and large medical practice websites. Despite differences in the resources accessed to perform information retrieval tasks, the clinical relevance and accuracy of information provided did not significantly differ between ChatGPT-4 and Google Search Engine., Clinical Relevance: Commercially available large language models (LLMs), such as ChatGPT-4, can perform diverse information retrieval tasks on-demand. An important medical information retrieval application for LLMs consists of the ability to provide comprehensive, relevant, and accurate information for various use cases such as investigation about a recently diagnosed medical condition or procedure. Understanding the performance and abilities of LLMs for use cases has important implications for deployment within health care settings., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.M.D. reports board or committee member for AAOS and the American Shoulder and Elbow Surgeons; other financial or material support from Biomet; editorial or governing board for Springer: publishing royalties, financial, or material support from Thieme; and paid consultant for Zimmer. J.S.D. reports board or committee member for the American Shoulder and Elbow Surgeons; IP royalties, paid consultant, paid presenter or speaker, and research support, Arthrex; editorial or governing board, Journal of Shoulder and Elbow Surgery; IP royalties from Linvatec; publishing royalties, financial, or material support from Thieme; stock or stock options from ViewFi; and publishing royalties, financial, or material support from Wolters Kluwer Health - Lippincott Williams & Wilkins. M.C.F. reports board or committee member for the American Shoulder and Elbow Surgeons; editorial or governing board for Arthroscopy and HSS Journal; and paid consultant for Stryker. L.V.G. reports paid consultant, paid presenter or speaker, research support from Biomet; IP royalties from and paid presenter or speaker for Exactech; editorial or governing board for HSS Journal; stock or stock options from Imagen and Responsive Arthroscopy; and paid presenter or speaker for Smith & Nephew. R.F.W. reports board or committee member for the American Orthopaedic Partners and IP royalties from Orthobio Therapeutics. K.N.K. reports editorial board for Arthroscopy and HSS Journal. All other authors (S.A.T., A.L., M.M., J.O.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: To provide a proof-of-concept analysis of the appropriateness and performance of ChatGPT-4 to triage, synthesize differential diagnoses, and generate treatment plans concerning common presentations of knee pain., Methods: Twenty knee complaints warranting triage and expanded scenarios were input into ChatGPT-4, with memory cleared prior to each new input to mitigate bias. For the 10 triage complaints, ChatGPT-4 was asked to generate a differential diagnosis that was graded for accuracy and suitability in comparison to a differential created by 2 orthopaedic sports medicine physicians. For the 10 clinical scenarios, ChatGPT-4 was prompted to provide treatment guidance for the patient, which was again graded. To test the higher-order capabilities of ChatGPT-4, further inquiry into these specific management recommendations was performed and graded., Results: All ChatGPT-4 diagnoses were deemed appropriate within the spectrum of potential pathologies on a differential. The top diagnosis on the differential was identical between surgeons and ChatGPT-4 for 70% of scenarios, and the top diagnosis provided by the surgeon appeared as either the first or second diagnosis in 90% of scenarios. Overall, 16 of 30 diagnoses (53.3%) in the differential were identical. When provided with 10 expanded vignettes with a single diagnosis, the accuracy of ChatGPT-4 increased to 100%, with the suitability of management graded as appropriate in 90% of cases. Specific information pertaining to conservative management, surgical approaches, and related treatments was appropriate and accurate in 100% of cases., Conclusions: ChatGPT-4 provided clinically reasonable diagnoses to triage patient complaints of knee pain due to various underlying conditions that were generally consistent with differentials provided by sports medicine physicians. Diagnostic performance was enhanced when providing additional information, allowing ChatGPT-4 to reach high predictive accuracy for recommendations concerning management and treatment options. However, ChatGPT-4 may show clinically important error rates for diagnosis depending on prompting strategy and information provided; therefore, further refinements are necessary prior to implementation into clinical workflows., Clinical Relevance: Although ChatGPT-4 is increasingly being used by patients for health information, the potential for ChatGPT-4 to serve as a clinical support tool is unclear. In this study, we found that ChatGPT-4 was frequently able to diagnose and triage knee complaints appropriately as rated by sports medicine surgeons, suggesting that it may eventually be a useful clinical support tool., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K.N.K. is on the editorial board of Arthroscopy and HSSJournal. J.C. is a board or committee member of American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, and International Society of Arthroscopy, Knee Surgery & Orthopaedic Sports Medicine (ISAKOS); is a paid consultant for Arthrex, ConMed Linvatec, Ossur, and Smith & Nephew; and is a paid presenter or speaker for Smith & Nephew. R.K.M. is a board or committee member of ISAKOS and is an unpaid consultant for Smith & Nephew. A.S.R. is a board or committee member of American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, and Eastern Orthopaedic Association; is on the editorial or governing board of American Journal of Sports Medicine, Current Trends in Musculoskeletal Medicine, Journal of Arthroplasty, Saunders/Mosby-Elsevier, and Springer; is a paid consultant for Anika, Bodycad, Cervos, ConMed Linvatec, Moximed, NewClip, Ranfac, and Smith & Nephew; receives research support from DePuy Mitek Synthes; receives intellectual property royalties from DePuy (A Johnson & Johnson Company); and owns stock or stock options in Enhatch. A.D.P. is a paid consultant for DePuy (A Johnson & Johnson Company), Smith & Nephew, and Zimmer; is a board or committee member of ISAKOS; and owns stock or stock options in LinkX, myGemini, myHealthTrack, Ostesys, and Vent Creativity. R.J.W. receives intellectual property royalties from Arthrex; is a paid consultant for Arthrex, JRF Ortho, and Lipogems; owns stock or stock options in BICMD, Cymedica, Engage Surgical, Gramercy Extremity Orthopedics, and Pristine Surgical, and RecoverX; and receives research support from Histogenics. All other authors (N.H.V., M.M., A.Z.L.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objective: (1) To develop a reliable grading system to assess the severity of posterior intervertebral osteophytes and (2) to investigate the impact of posterior intervertebral osteophytes on clinical outcomes after L5-S1 decompression and fusion through anterior lumbar interbody fusion (ALIF) and minimally-invasive transforaminal lumbar interbody fusion (MIS-TLIF)., Background: There is limited evidence regarding the clinical implications of posterior lumbar vertebral body osteophytes for ALIF and MIS-TLIF surgeries and there are no established grading systems that define the severity of these posterior lumbar intervertebral osteophytes., Patients and Methods: A retrospective analysis of patients undergoing L5-S1 ALIF or MIS-TLIF was performed. Preoperative and postoperative patient-reported outcome measures of the Oswestry Disability Index (ODI) and leg Visual Analog Scale (VAS) at 2-week, 6-week, 12-week, and 6-month follow-up time points were assessed. Minimal clinically important difference (MCID) for ODI of 14.9 and VAS leg of 2.8 were utilized. Osteophyte grade was based on the ratio of osteophyte length to foraminal width. "High-grade" osteophytes were defined as a maximal osteophyte length >50% of the total foraminal width., Results: A total of 70 consecutive patients (32 ALIF and 38 MIS-TLIF) were included in the study. There were no significant differences between the two cohorts in patient-reported outcome measures or achievement of MCID for Leg VAS or ODI preoperatively or at any follow-ups. On multivariate analysis, neither the surgical approach nor the presence of high-grade foraminal osteophytes was associated with leg VAS or ODI scores at any follow-up time point. In addition, neither the surgical approach nor the presence of high-grade foraminal osteophytes was associated with the achievement of MCID for leg VAS or ODI at 6 months., Conclusion: ALIF and MIS-TLIF are both valid options for treating degenerative spine conditions and lumbar radiculopathy, even in the presence of high-grade osteophytes that significantly occupy the intervertebral foramen., Level of Evidence: 3., Competing Interests: M.S.F has the following disclosures: Johnson & Johnson: Paid consultant. S.Q. has the following disclosures: AMOpportunities: Other financial or material support; Annals of Translational Medicine: Editorial or governing board; Association of Bone and Joint Surgeons: Board or committee member; Cervical Spine Research Society: Board or committee member; Contemporary Spine Surgery: Editorial or governing board; Globus Medical: IP royalties; Paid consultant; Paid presenter or speaker; Hospital Special Surgery Journal: Editorial or governing board; HS2, LLC: Stock or stock Options; International Society for the Advancement of Spine Surgery (ISASS) - Program Committee member: Board or committee member; Lifelink.com: Other financial or material support; Lumbar Spine Research Society: Board or committee member; Minimally Invasive Spine Study Group: Board or committee member; North American Spine Society: Board or committee member; Simplify Medical, Inc.: Other financial or material support; Society of Minimally Invasive Spine Surgery (SMISS) - Program Committee member: Board or committee member; Spinal Simplicity: Other financial or material support; SpineGuard, Inc.: Paid consultant; Stryker: IP royalties; Paid consultant; Surgalign: Paid consultant; Tissue Differentiation Intelligence: Stock or stock Options; Viseon, Inc.: Paid consultant; Research support. S.I. has the following disclosures: Globus Medical: Paid presenter or speaker; Stryker: Paid presenter or speaker; Vertebral Columns/International Society for the Advancement of Spine Surgery (ISASS): Editorial or governing board. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Cross-sectional survey and retrospective review of prospectively collected data., Objective: To explore how patients perceive their decision to pursue spine surgery for degenerative conditions and evaluate factors correlated with decisional regret., Summary of Background Data: Prior research shows that one-in-five older adults regret their decision to undergo spinal deformity surgery. However, no studies have investigated decisional regret in patients with degenerative conditions., Methods: Patients who underwent cervical or lumbar spine surgery for degenerative conditions (decompression, fusion, or disk replacement) between April 2017 and December 2020 were included. The Ottawa Decisional Regret Questionnaire was implemented to assess prevalence of decisional regret. Questionnaire scores were used to categorize patients into low (<40) or medium/high (≥40) decisional regret cohorts. Patient-reported outcome measures (PROMs) included the Oswestry Disability Index, Patient-reported Outcomes Measurement Information System, Visual Analog Scale (VAS) Back/Leg/Arm, and Neck Disability Index at preoperative, early postoperative (<6 mo), and late postoperative (≥6 mo) timepoints. Differences in demographics, operative variables, and PROMs between low and medium/high decisional regret groups were evaluated., Results: A total of 295 patients were included (mean follow-up: 18.2 mo). Overall, 92% of patients agreed that having surgery was the right decision, and 90% would make the same decision again. In contrast, 6% of patients regretted the decision to undergo surgery, and 7% noted that surgery caused them harm. In-hospital complications (P=0.02) and revision fusion (P=0.026) were significantly associated with higher regret. The medium/high decisional regret group also exhibited significantly worse PROMs at long-term follow-up for all metrics except VAS-Arm, and worse achievement of minimum clinically important difference for Oswestry Disability Index (P=0.007), Patient-Reported Outcomes Measurement Information System (P<0.0001), and VAS-Leg (P<0.0001)., Conclusions: Higher decisional regret was encountered in the setting of need for revision fusion, increased in-hospital complications, and worse PROMs. However, 90% of patients overall were satisfied with their decision to undergo spine surgery for degenerative conditions. Current tools for assessing patient improvement postoperatively may not adequately capture the psychosocial values and patient expectations implicated in decisional regret., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The ankle is one of the anatomic sites most frequently injured in National Football League (NFL) players. Ankle injuries have previously been shown to have long-lasting negative impacts, and have been associated with impaired athletic performance. The aim of this study was to use fantasy football points as a metric to evaluate the impact of ankle injuries on NFL offensive skill player performance., Methods: An open-access online database was used to identify NFL players who sustained ankle injuries from 2009 to 2020. Another public online database was used to determine fantasy points and other performance metrics for injured offensive skill players in the seasons before and after their ankle injury. Injured players were matched to a healthy control by position, age, and BMI. Paired T-tests were performed to evaluate performance metrics before and after the ankle injury. An ANCOVA was performed to assess the effect of return to play (RTP) time and injury type on fantasy performance., Results: 303 players with ankle injuries were included. Fantasy output, including average points per game (PPG) and total fantasy points accrued in one season, significantly decreased in the season following a player's ankle injury (p < 0.0001). In running backs, tight ends, and wide receivers, performance significantly decreased in every metric evaluated (p < 0.0001). In quarterbacks, there was no significant change in performance, except for a decrease in the number of games played (p = 0.0033) and in the number of interceptions thrown (p = 0.029)., Conclusion: Assessing fantasy football output revealed a decrease in player performance in the season following an ankle injury, especially in route-running players. These results can be used to inform injury prevention and rehabilitation practices in the NFL., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Study Design: Retrospective review of prospectively collected data., Objective: To identify the risk factors associated with failure to respond to erector spinae plane (ESP) block following minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)., Summary of Background Data: ESP block is an emerging opioid-sparing regional anesthetic that has been shown to reduce immediate postoperative pain and opioid demand following MI-TLIF-however, not all patients who receive ESP blocks perioperatively experience a reduction in immediate postoperative pain., Methods: This was a retrospective review of consecutive patients undergoing 1-level MI-TLIF who received ESP blocks by a single anesthesiologist perioperatively at a single institution. ESP blocks were administered in the OR following induction. Failure to respond to ESP block was defined as patients with a first numerical rating scale (NRS) score post-surgery of >5.7 (mean immediate postoperative NRS score of control cohort undergoing MI TLIF without ESP block). Multivariable logistic regressions were performed to identify predictors for failure to respond to ESP block., Results: A total of 134 patients were included (mean age 60.6 years, 43.3% females). The median and interquartile range (IQR) first pain score post-surgery was 2.5 (0.0-7.5). Forty-nine (36.6%) of patients failed to respond to ESP block. In the multivariable regression analysis, several independent predictors for failure to respond to ESP block following MI TLIF were identified: female sex (OR 2.33, 95% CI 1.04-5.98, P=0.040), preoperative opioid use (OR 2.75, 95% CI 1.03- 7.30, P=0.043), anxiety requiring medication (OR 3.83, 95% CI 1.27-11.49, P=0.017), and hyperlipidemia (OR 3.15, 95% CI 1.31-7.55, P=0.010)., Conclusions: Our study identified several predictors for failure to respond to ESP block following MI TLIF including female sex, preoperative opioid pain medication use, anxiety, and hyperlipidemia. These findings may help inform the approach to counseling patients on perioperative outcomes and pain expectations following MI-TLIF with ESP block., Level of Evidence: III., Competing Interests: Conflicts of Interest: Sheeraz Qureshi has the following disclosures: AMOpportunities: Other financial or material support; Annals of Translational Medicine: Editorial or governing board; Association of Bone and Joint Surgeons: Board or committee member; Cervical Spine Research Society: Board or committee member; Contemporary Spine Surgery: Editorial or governing board; Globus Medical: IP royalties; Paid consultant; Paid presenter or speaker; Hospital Special Surgery Journal: Editorial or governing board; HS2, LLC: Stock or stock Options; International Society for the Advancement of Spine Surgery (ISASS) - Program Committee member: Board or committee member; Lifelink.com: Other financial or material support; Lumbar Spine Research Society: Board or committee member; Minimally Invasive Spine Study Group: Board or committee member; North American Spine Society: Board or committee member; Simplify Medical, Inc.: Other financial or material support; Society of Minimally Invasive Spine Surgery (SMISS) - Program Committee member: Board or committee member; Spinal Simplicity: Other financial or material support; SpineGuard, Inc.: Paid consultant; Stryker: IP royalties; Paid consultant; Surgalign: Paid consultant; Tissue Differentiation Intelligence: Stock or stock Options; Viseon, Inc.: Paid consultant; Research support; Clinical Spine Surgery: Editorial or governing board., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Interpreting clinical relevance of randomized clinical trials (RCTs) is challenging when P-values are marginally above or below the P = .05 threshold. This study examined the robustness of statistically insignificant mortality events from RCTs comparing hemiarthroplasty femoral fixation for displaced intracapsular hip fractures through the reverse fragility index (RFI)., Methods: RCTs were identified using Pubmed, OVID/Medline, and Cochrane databases. Mortality endpoints were stratified into 3 categories: (1) within 30-days, (2) within 90-days, and (3) at latest follow-up. The RFI was derived by manipulating reported mortality events utilizing a contingency table while maintaining a constant number of participants. The reverse fragility quotient (RFQ) was quantified by dividing the RFI by the study sample., Results: Eight RCTs (2,494 participants) were included. The median RFI and RFQ within 30-days was 3.0 (interquartile range [IQR]: 3.0 to 6.0) and 0.016 (IQR: 0.015 to 0.021), suggesting nonsignificant findings were contingent on 1.6 mortality events/100 participants. The median RFI and RFQ within 90-days was 6.0 (IQR: 4.0 to 7.0) and 0.028 (IQR: 0.024 to 0.038), suggesting nonsignificant findings were contingent on 2.8 mortality events/100 participants. At latest follow-up, the median RFI and RFQ was 7.0 (IQR: 6.0 to 12.0) and 0.038 (IQR: 0.029 to 0.054), suggesting nonsignificant findings were contingent on only 3.8 mortality events/100 participants. Median loss to follow-up was 16.0 (IQR: 11.0 to 58.0; 228% greater than RFI), and exceeded the RFI in 6/7(85.7%) studies., Conclusions: A small number of events (median of 7) was required to convert a statistically nonsignificant finding to one that is significant for the endpoint of mortality. The median loss to follow-up exceeded the median RFI by greater than 200%, suggesting methodological limitations such as patient allocation could alter conclusions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background Context: Navigation and robotic technologies have emerged as an alternative option to conventional freehand techniques for pedicle screw insertion. However, the effectiveness of these technologies in reducing the perioperative complications of spinal fusion surgery remains limited due to the small cohort size in the existing literature., Purpose: To investigate whether utilization of robotically navigated pedicle screw insertion can reduce the perioperative complications of spinal fusion surgery-including reoperations-with a sizeable cohort., Study Design: Retrospective study., Patient Sample: Patients who underwent primary lumbar fusion surgery between 2019 and 2022., Outcome Measures: Perioperative complications including readmission, reoperation, its reasons, estimated blood loss, operative time, and length of hospital stay., Methods: Patients' data were collected including age, sex, race, body mass index, upper-instrumented vertebra, lower-instrumented vertebra, number of screws inserted, and primary procedure name. Patients were classified into the following two groups: freehand group and robot group. The variable-ratio greedy matching was utilized to create the matched cohorts by propensity score and compared the outcomes between the two group., Results: A total of 1,633 patients who underwent primary instrumented spinal lumbar fusion surgery were initially identified (freehand 1,286; robot 347). After variable ratio matching was performed with age, sex, body mass index, fused levels, and upper instrumented vertebrae level, 694 patients in the freehand group and 347 patients in robot groups were selected. The robot group showed less estimated blood loss (418.9±398.9 vs 199.2±239.6 ml; p<.001), shorter LOS (4.1±3.1 vs 3.2±3.0 days; p<.001) and similar operative time (212.5 vs 222.0 minutes; p=.151). Otherwise, there was no significant difference in readmission rate (3.6% vs 2.6%; p=.498), reoperation rate (3.2% vs 2.6%; p=.498), and screw malposition requiring reoperation (five cases, 0.7% vs one case, 0.3%; p=1.000)., Conclusions: Perioperative complications requiring readmission and reoperation were similar between fluoroscopy guided freehand and robotic surgery. Robot-guided pedicle screw insertion can enhance surgical efficiency by reducing intraoperative blood loss and length of hospital stay without extending operative time., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.

Background: Vascular anomalies and tumors are common in the head, neck, and craniofacial areas and are associated with abnormalities in the angiomatous architecture. However, the etiology and molecular basis for the pathogenesis of most vascular lesions are still unknown. Pericytes are mural cells that surround endothelial cells. Besides angiogenesis and other physiological functions, pericytes play an important role in vascularized tissue repair and as resident mesenchymal stem/progenitor cells. Perivascular cells demonstrate a distinct immunohistochemical profile, including expression of alpha-smooth muscle actin (α-SMA), CD146, CD105, and PDGFRβ, without endothelial differentiation (absence of CD31 and CD34 immunoreactivity). These pericyte markers have been shown to be expressed in soft tissue hemangiomas. However, they have not been fully examined in intraosseous hemangiomas., Methods: In this study, we compared mesenchymal stem cell (MSC) expression of CD146 and α-SMA markers in pericytes from hemangiomas from different tissues and malignant vascular tumors., Results: The results demonstrated an increased expression of pericyte markers in perivascular cells of benign hemangiomas, especially intraosseous hemangiomas and a significantly reduced expression of pericyte markers in malignant angiosarcomas., Conclusion: The evidence provides insight into the function of pericytes in vascular tumors and suggests their role in vascular tumor disease types., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to assess the outcomes of patients with predominant back pain (pBP) undergoing minimally invasive decompression surgery compared with patients with nonpredominant back pain (npBP)., Methods: This was a retrospective cohort study. Patients were divided into two groups based on the presenting complaint: 1) pBP, defined as visual analog scale (VAS) back pain score > VAS leg pain score; and 2) npBP. Changes in patient-reported outcome measures (PROMs) were compared at the early (< 6 months) and late (≥ 6 months) postoperative time points. Outcomes measures were: 1) PROMs (Oswestry Disability Index [ODI], VAS back and leg pain scores, 12-Item Short-Form Health Survey Physical Component Score [SF-12 PCS], and Patient-Reported Outcomes Measurement Information System Physical Function [PROMIS PF]), and 2) minimal clinically important difference (MCID) achievement rate and time. For the late MCID achievement point, a second analysis was conducted restricting VAS back and leg pain scores only to patients with preoperative scores ≥ 5., Results: Three hundred ninety patients were included (126 with pBP and 264 with npBP). There were no differences in patient demographics and operated levels. There were no differences in preoperative ODI, SF-12 PCS, and PROMIS PF scores. The pBP cohort had a significantly greater preoperative VAS back pain score than the npBP cohort, whereas the npBP cohort had a significantly greater preoperative VAS leg pain score than the pBP cohort. There were no differences in the absolute values or changes in ODI, VAS back pain, SF-12 PCS, and PROMIS PF scores at any time point. There was a significant difference in the early VAS leg pain scores (greater in npBP) that disappeared by the late postoperative time point. There was no difference in the MCID achievement rate in the ODI, SF-12 PCS, or PROMIS PF scores. By the late postoperative time point, 51.2% and 55.3% achieved an MCID on the ODI, 58.1% and 62.7% on the SF-12 PCS, 60% and 67.6% on the PROMIS PF, 81.1% and 73.2% on VAS back pain scores for those with preoperative scores ≥ 5, and 72% and 83.6% on VAS leg pain scores for those with preoperative scores ≥ 5 for the pBP and npBP cohorts, respectively. Additionally, there were no differences in time to MCID achievement for any PROMs., Conclusions: The pBP and npBP cohorts showed similar improvement in PROMs and MCID achievement rates. This result shows that minimally invasive laminectomy is equally effective for patients presenting with pBP or npBP.

Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.

Background: Neurologic injury is a rare and potentially devastating complication of shoulder arthroplasty. Patients typically present with a mixed plexopathy or mononeuropathy, most commonly affecting the axillary and radial nerves. Given the paucity of studies available on the topic, our goal was to elucidate the prevalence of nerve injury after shoulder arthroplasty and to describe the treatment course and outcomes of neurologic injuries., Methods: This is a retrospective case-control study performed at a single, urban, academic institution. Consecutive patients who underwent anatomic total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (RSA) by a single surgeon from 2014 to 2020 were reviewed, and patients with a documented nerve injury were identified. A control group of patients without nerve injury were selected in a 2:1 ratio controlling for age and procedure type (TSA vs. RSA; primary vs. revision). Data collected included demographics, comorbidities as per the Charlson Comorbidity Index, radiographic evaluations, surgical and implant details, patient-reported outcome measures, and perioperative complications., Results: Of 923 patients, 33 (3.6%) sustained an iatrogenic nerve injury: 10 (2.1%) after TSA, 23 (5.0%) after RSA, and 3 (7.8%) after revision arthroplasty. Axillary mononeuropathy was most common (42%), followed by brachial plexopathies (18%). There was no significant difference in age, sex, race, body mass index, and preoperative diagnoses between groups. Patients with nerve injury had fewer comorbidities (Charlson Comorbidity Index <3, 33 vs. 65%, P <.001). Patients with nerve injury had higher rates of cervical spine pathology (15 vs. 6%; P  = .15) and increased postoperative lateralization (8.9 mm [7.2] vs. 5.5 mm [7.3]; P <.06). The majority (91%) were managed with observation alone. Three (9%) underwent an additional procedure: carpal tunnel release (1, 3%), ulnar nerve decompression (1, 3%), and ulnar nerve transposition (1, 3%) for peripheral compressive neuropathies. At the final follow-up, 19 (57%) nerves fully recovered, and 14 (43%) showed mild residual sensorimotor dysfunction. The mean time to first sign of recovery and ultimate recovery were 11 (7.2) and 36 (23.5) weeks, respectively. At the final follow-up, patients with nerve injury performed worse on patient-reported outcomes, including visual analog score pain (2.2 vs. 1.0, P <.001), American Shoulder and Elbow Surgeons score (67.8 vs. 84.8, P <.001), and Single Assessment Numeric Evaluation scores (62 vs. 77, P  = .009)., Discussion: Nerve injury after shoulder arthroplasty is rare, occurring in 3.6% of our patient population. Axillary mononeuropathy and brachial plexopathies are the most common. Most patients can be managed expectantly with observation and will recover at least partial nerve function, although clinical outcomes remain inferior to those without nerve complication., (© 2022 Published by Elsevier Inc. on behalf of American Shoulder & Elbow Surgeons.)

The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2 (GESS v2 https://shiny.ph.iu.edu/GESS&#95;v2/) is an updated version of GESS, which has offered a handy query platform to analyze single-nucleotide variants (SNVs) on millions of high coverages and high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes provided by the Global Initiative on Sharing Avian Influenza Data (GISAID). Including the tools in the first version, the GESS v2 is embedded with new functions, which allow users to search SNVs, given the viral nucleotide or amino acid sequence. The GESS v2 helps users to identify SNVs or SARS-CoV-2 lineages enriched in countries of user's interest and show the migration path of a selected lineage on a world map during specific time periods chosen by the users. In addition, the GESS v2 can recognize the dynamic variations of newly emerging SNVs in each month to help users monitor SNVs, which will potentially become dominant soon. More importantly, multiple sets of analyzed results about SNVs can be downloaded directly from the GESS v2 by which users can conduct their own independent research. With these significant updates, the GESS v2 will continue to serve as a public open platform for researchers to explore SARS-CoV-2 evolutionary patterns from the perspectives of the prevalence and impact of SNVs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Liu, Fang, Lu, Shen, Yang, Hu, Yang and Wan.)

By analyzing newly collected SARS-CoV-2 genomes and comparing them with our previous study about SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality-related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion., (© 2021 Wiley Periodicals LLC.)

PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function. Here, we identify PARP7 as a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 restores type I interferon (IFN) signaling responses to nucleic acids in tumor models. Restored signaling can directly inhibit cell proliferation and activate the immune system, both of which contribute to tumor regression. Oral dosing of the PARP7 small-molecule inhibitor, RBN-2397, results in complete tumor regression in a lung cancer xenograft and induces tumor-specific adaptive immune memory in an immunocompetent mouse cancer model, dependent on inducing type I IFN signaling in tumor cells. PARP7 is a therapeutic target whose inhibition induces both cancer cell-autonomous and immune stimulatory effects via enhanced IFN signaling. These data support the targeting of a monoPARP in cancer and introduce a potent and selective PARP7 inhibitor to enter clinical development., Competing Interests: Declaration of interests J.M.G., M.M.V., R.P.A., K.K., K.G.K.-B., B.G., A.Z.L., J.R. Molina, E.M., K.K.S., T.J.W., D.J.B., C.R.M., Y.R., M.N., Z.A.V., S.P.N., E.B., J.-R. Mo, W.D.C., A.S.A.M., J.S., L.U., K.W.K., V.M.R., and H.K. are all employees and shareholders of Ribon Therapeutics at the time of data collection. P.E.R. served as a consultant to Ribon Therapeutics, and T.J.M. is a founder and shareholder in Ribon Therapeutics. M.M.V., K.K.S., and K.W.K. are inventors on US Patent Nos. 10550105, 10870641, and 11014913, which are related to RBN-2397 and assigned to Ribon Therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

PARP14 has been implicated by genetic knockout studies to promote protumor macrophage polarization and suppress the antitumor inflammatory response due to its role in modulating interleukin-4 (IL-4) and interferon-γ signaling pathways. Here, we describe structure-based design efforts leading to the discovery of a potent and highly selective PARP14 chemical probe. RBN012759 inhibits PARP14 with a biochemical half-maximal inhibitory concentration of 0.003 μM, exhibits >300-fold selectivity over all PARP family members, and its profile enables further study of PARP14 biology and disease association both in vitro and in vivo. Inhibition of PARP14 with RBN012759 reverses IL-4-driven protumor gene expression in macrophages and induces an inflammatory mRNA signature similar to that induced by immune checkpoint inhibitor therapy in primary human tumor explants. These data support an immune suppressive role of PARP14 in tumors and suggest potential utility of PARP14 inhibitors in the treatment of cancer., Competing Interests: Declaration of interests L.B.S., K.K.S., M.M.V., and K.W.K. are co-inventors on pending patent application WO 2019/126443 and issued U.S. Pat. No. 10,562,891, both of which relate to quinazolinone inhibitors of PARP14 for the treatment of cancer and other diseases and are assigned to Ribon Therapeutics, Inc., of Cambridge, MA, USA., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

PARP14 is an interferon-stimulated gene that is overexpressed in multiple tumor types, influencing pro-tumor macrophage polarization as well as suppressing the antitumor inflammation response by modulating IFN-γ and IL-4 signaling. PARP14 is a 203 kDa protein that possesses a catalytic domain responsible for the transfer of mono-ADP-ribose to its substrates. PARP14 also contains three macrodomains and a WWE domain which are binding modules for mono-ADP-ribose and poly-ADP-ribose, respectively, in addition to two RNA recognition motifs. Catalytic inhibitors of PARP14 have been shown to reverse IL-4 driven pro-tumor gene expression in macrophages, however it is not clear what roles the non-enzymatic biomolecular recognition motifs play in PARP14-driven immunology and inflammation. To further understand this, we have discovered a heterobifunctional small molecule designed based on a catalytic inhibitor of PARP14 that binds in the enzyme's NAD + -binding site and recruits cereblon to ubiquitinate it and selectively target it for degradation., (© 2021 Wiley-VCH GmbH.)

Poly(ADP-ribose) polymerase (PARP) enzymes use nicotinamide adenine dinucleotide (NAD + ) to modify up to seven different amino acids with a single mono(ADP-ribose) unit (MARylation deposited by PARP monoenzymes) or branched poly(ADP-ribose) polymers (PARylation deposited by PARP polyenzymes). To enable the development of tool compounds for PARP monoenzymes and polyenzymes, we have developed active site probes for use in in vitro and cellular biophysical assays to characterize active site-directed inhibitors that compete for NAD + binding. These assays are agnostic of the protein substrate for each PARP, overcoming a general lack of knowledge around the substrates for these enzymes. The in vitro assays use less enzyme than previously described activity assays, enabling discrimination of inhibitor potencies in the single-digit nanomolar range, and the cell-based assays can differentiate compounds with sub-nanomolar potencies and measure inhibitor residence time in live cells., Competing Interests: Declaration of Interests All authors are employees and shareholders of Ribon Therapeutics and a patent on this work has been granted (WO/2019/212946)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Poly-ADP-ribose polymerases (PARPs) are a family of enzymes responsible for transferring individual or chains of ADP-ribose subunits to substrate targets as a type of post-translational modification. PARPs regulate a wide variety of important cellular processes, ranging from DNA damage repair to antiviral response. However, most research to date has focused primarily on the polyPARPs, which catalyze the formation of ADP-ribose polymer chains, while the monoPARPs, which transfer individual ADP-ribose monomers, have not been studied as thoroughly. This is partially due to the lack of robust assays to measure mono-ADP-ribosylation in the cell. In this study, the recently developed MAR/PAR antibody has been shown to detect mono-ADP-ribosylation in cells, enabling the field to investigate the function and therapeutic potential of monoPARPs. In this study, the antibody was used in conjunction with engineered cell lines that overexpress various PARPs to establish a panel of assays to evaluate the potencies of literature-reported PARP inhibitors. These assays should be generally applicable to other PARP family members for future compound screening efforts. A convenient and generalizable workflow to identify and validate PARP substrates has been established. As an initial demonstration, aryl hydrocarbon receptor was verified as a direct PARP7 substrate and other novel substrates for this enzyme were also identified and validated. This workflow takes advantage of commercially available detection reagents and conventional mass spectrometry instrumentation and methods. Ultimately, these assays and methods will help drive research in the PARP field and benefit future therapeutics development., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited data are available in relation to the clinical features of PIBO undergoing prolonged nebulization treatment with budesonide, terbutaline and ipratropium bromide. This retrospective study aimed to outline the features of clinical, high-resolution computed tomography (HRCT) and pulmonary function test (PFT) of PIBO, undergoing maintenance therapy utilizing a triple nebulization treatment and to determine the factors associated with prognosis., Methods: Children diagnosed with PIBO were followed up between April 2014 and March 2017. The clinical features after maintenance nebulization treatment for 12 months were thereafter summarized., Results: Thirty patients, 21 boys and 9 girls, were enrolled in the study. The median age of patients was 17.4 months, with a range between 3.0 and 33 months. Persistent coughing and wheezing were detected whilst wheezing and crackles were the common manifestations presented. HRCT scans revealed patchy ground and glass opacity, while PFT showed fixed airway obstruction in all patients. Four patients were lost during follow-up. After treatment, the clinical symptoms were improved greatly in all patients (P < 0.01). The mean increase in the percentage of TPEF%TE and VPEF%VE were improved greatly (P < 0.01). Images of the HRCT scan indicated marked improvements in 18 patients (81.8%) in comparison with scans obtained pre-treatment., Conclusions: Our data suggest a potential role of long-term nebulization treatment of budesonide, terbutaline, ipratropium bromide on PIBO, due to its efficacy as indicated in the improved clinical symptoms, pulmonary functions and CT manifestations identified in the children. New prospective and controlled studies are required to confirm this proposition.

Background: The accuracy of nasopharyngeal aspirate (NPA) specimens in detecting lower respiratory pathogens remains controversial. The objective of this study was to evaluate the diagnostic accuracy of aspirates (NPAs) specimen in lower respiratory tract infections (LRTIs) in children., Methods: The prospective study was designed to collect the data of paired NPAs and bronchoalveolar lavage fluids from children with acute LRTIs from January 2013 to December 2015. All specimens were subjected to pathogen detection: bacterial detection by culture, Mycoplasma pneumoniae (Mp) detection by polymerase chain reaction assay and virus (influenza A and B viruses, parainfluenza virus [PIV] Types 1 and 3, respiratory syncytial virus, and adenovirus) detection by immunofluorescence assay. The diagnostic accuracy analysis of NPAs was stratified by age ≤3 years (n = 194) and >3 years (n = 294)., Results: We collected paired specimens from 488 children. The positive rate of pathogen was 61.6%. For Streptococcus pneumoniae, NPA culture had the specificity of 89.9% and negative predictive value of 100% in age ≤3 years, the specificity of 97.2% and negative predictive value of 98.9% in age >3 years. For Mp, the positive predictive values of NPA was 77.4% in children ≤3 years, and 89.1% in children >3 years. For PIV III, NPA specimen had the specificity of 99.8% and negative predictive value of 96.5% in children ≤3 years. For adenovirus, NPA had the specificity of 97.8% and negative predictive value of 98.4% in age ≤3 years, the specificity of 98.9% and negative predictive value of 99.3% in age >3 years., Conclusions: NPAs are less invasive diagnostic respiratory specimens, a negative NPA result is helpful in "rule out" lower airway infection; however, a positive result does not reliably "rule in" the presence of pathogens.

Interleukin-6 (IL-6) participates in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch homolog 2 (Sbno2) as an IL-6-stimulated gene in murine astrocytes. Sbno2 is a mouse homolog of the sno gene in Drosophila but little is known about the regulation or function of the mammalian gene. Here we examined the regulation of the Sbno2 gene in astrocytes in vitro and in the murine CNS following systemic endotoxin administration. In murine and human cultured astrocytes, Sbno2 gene expression was significantly upregulated in a dose- and time-dependent fashion by hyper-IL-6 (IL-6 + soluble IL-6 receptor). The level of Sbno2 mRNA was also upregulated significantly in murine astrocytes by other glycoprotein130 cytokine-family members and the pro-inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha. These changes were reflected by corresponding alterations in the level of the SBNO2 protein. Inhibiting protein synthesis resulted in higher Sbno2 mRNA and did not abolish the upregulation of Sbno2 mRNA mediated by hyper-IL-6. Inhibition of transcription led to a rapid reduction in hyper-IL-6-induced Sbno2 mRNA in astrocytes suggesting that the Sbno2 mRNA is quite unstable. Following intra-peritoneal lipopolysaccharide injection in mice, Sbno2 mRNA levels in the brain were significantly increased. Cellular localization studies revealed that this increase in Sbno2 mRNA occurred predominantly in astrocytes and in the choroid plexus and in some microglia, endothelial cells, and neurons. These findings are consistent with SBNO2 functioning as an acute inflammatory response gene in astrocytes as well as other cells in the CNS., (© 2015 The Authors. Glia Published by Wiley Periodicals, Inc.)

Nerve cell injury associated with apoptosis plays an important role in the development of diabetic peripheral neuropathy (DPN). However, it remains unclear whether preexisting or potential neurocyte damage induced by hyperglycemia increases sensitivity to local anesthetics. SH-SY5Y cells were pretreated with a high concentration of glucose in vitro, to imitate DPN prior to administration of bupivacaine or placebo. Cell viability and apoptosis were investigated with a CCK-8 assay and flow cytometry, respectively. In addition, mitochondrial membrane potential, reactive oxygen species (ROS), mitochondrially generated ROS, and activity of mitochondrial complexes I and III were studied to explore the molecular mechanism of bupivacaine-induced mitochondrial injury. Grp78 and caspase-12 expression were measured by qRT-PCR and Western blot, representing endoplasmic reticulum (ER) stress. Cell structure was also assessed via transmission electron microscopy. Incubation with bupivacaine decreased the activity of mitochondrial complexes I and III; increased ROS production at cell and mitochondrial levels, mitochondrial potential depolarization, and Grp78 and caspase-12 expression at both transcription and translation levels; and affected cell structure, which could be enhanced by glucose pretreatment. These findings indicate that mitochondrial dysfunction and ER stress related to ROS are involved in bupivacaine-induced apoptosis and may be enhanced by glucose administration., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: To study the effects of prolonged 75% oxygen exposure on the expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) in the neonatal rat lungs and to elucidate the effects of prolonged exposure of high concentration of oxygen on lung vascular development and its relationship with bronchopulmonary dysplasia (BPD)., Methods: Forty eight Sprague-Dawley rat pups were randomly exposed to air (control group) and 75% oxygen (experimental group) 12 hrs after birth. The rats were sacrificed 7, 14 and 21 days after exposure and their lungs were sampled. The lung sections were stained with hematoxylin and eosin for histological evaluation. Expression of VEGF, VEGFR1 and VEGFR2 protein and mRNA was detected by immunohistochemistry and RT-PCR., Results: After being exposed to 75% oxygen for 21 days, lung tissues had pathological changes as 'new' BPD. Expressions of VEGF protein (10.9 + or - 2.7 vs 30.8 + or - 6.4), VEGFR1 protein (5.4 + or - 1.4 vs 15.6 + or - 3.4) and VEGFR2 protein (11.3 + or - 2.6 vs 21.7 + or - 4.5) on day 21 in the experimental group decreased significantly as compared with the control group (p<0.05). The expression of VEGF mRNA (1.6 vs 3.3), VEGFR1 mRNA (0.4 vs 6.6) and VEGFR2 mRNA (0.5 vs 4.9) on day 21 in the experimental group also decreased significantly as compared with the control group (p<0.05)., Conclusions: Prolonged exposure of high concentration of oxygen may cause BPD possibly by inhibiting lung vascular development in neonatal rats.

Objective: Mycoplasma pneumoniae (Mp) infection is one of major causes of community-acquired pneumonia. Isolation and culture of Mp are very difficult, fluorescent quantitative PCR is a new technique to detect Mp. The aim of this study was to explore the diagnostic value of fluorescent quantitation PCR for Mp infection., Method: Mp-DNA from the deep respiratory tract secretion of children suffering from pneumonia was tested by a fluorescent quantitative PCR. Totally 256 cases who were positive for Mp DNA were enrolled into this study, 164 (64.1%) were male, 92 (35.9%) were female; the age ranged from 9 days to 16 years. All the patients also had results of Mp-IgM test. These patients were divided into 2 groups according to the result of Mp-IgM detection, namely, Mp-IgM positive and negative groups. Area under the roc curve (Az) was used as the index to evaluate the diagnostic value of fluorescent quantitation PCR for Mp detection. The number of Mp-DNA copies, age and course of disease of the 2 groups were also compared., Results: (1) Diagnostic accuracy of fluorescent quantitative PCR for detecting Mp infection was that Az = 0.641. (2) The number of copies of the cases in Mp-IgM positive group was 5.42 +/- 1.26 [log(Mp-DNA copy/ml)], while that of Mp-IgM-negative group was 4.87 +/- 1.29 [log(Mp-DNA copy/ml), t = 3.43, P < 0.05]. (3) The age of Mp-IgM positive group was dramatically younger than Mp-IgM negative group (P < 0.001)., Conclusion: The diagnostic accuracy of fluorescent quantitative PCR for mycoplasma pneumoniae (Mp) infection is low; however for children whose immunologic systems are not fully developed, this technique has some diagnostic value, and higher number of Mp-DNA copies may support diagnosis of Mp infection.

Objective: To explore the association of interleukin 8 (IL-8)-251T/A and 781 C/T single nucleotide polymorphisms (SNPs) with the susceptibility of infants and young children to respiratory syncytial virus (RSV) infection., Method: This study included 101 hospitalized patients under 2 years of age who suffered from RSV pneumonia, 108 hospitalized patients under 2 years of age with non-RSV pneumonia and 35 core families with a child hospitalized for RSV pneumonia. Genotypes of 2 SNP loci in all enrolled persons were defined by allele specific polymerase chain reaction (AS-PCR), and confirmed by gene sequencing. The allele's frequencies of SNPs were analyzed with case-control study and transmission disequilibrium test (TDT), linkage of 2 loci and haplotypes composed of the 2 loci were also studied., Results: (1) The frequency of IL-8-251T in cases was dramatically high (OR = 2.08, P = 0.0002, case-control study; LRT = 14.31, P = 0.0008, TDT). (2) IL-8-251T and 781C was linkaged (D' = 0.607 +/- 0.03, r(2) = 0.2861, P = 0.0000). (3) Haplotype of TC was significantly high in cases (P = 0.01)., Conclusion: These findings support that haplotype of TC composed of IL-8-251T and 781C is associated with the susceptibility to RSV, namely, some RSV predisposing genes are located in the gene fragment including TC haplotype or linked tightly with this gene fragment.