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Background: We set out to investigate prospectively the morbidity rate for gynecological laparoscopy patients at a tertiary care center.Methods: We prospectively recorded data on 743 laparoscopic procedures performed between January 1, 1992 and December 31, 1996. The procedures included 36 diagnostic laparoscopies (4.8%), 115 laparoscopies carried out for minor surgical acts (15.4%), 523 for major surgical acts (70.4%), and 69 for advanced surgical acts (9. 4%). A total of 127 patients had a history of prior laparotomy (17%). All those procedures were performed by young senior surgeons. We defined a complication as an event that had modified the usual course of the procedure or of the postoperative period. For statistical analysis, we used the chi-squared test or Fisher's exact test.Results: Complications occurred in 22 cases; the overall complication rate was 2.9% when all events were considered. One complication (injury of the left primitive iliac artery) was related to insertion of the Veress needle (0.13%). A total of 2,578 trocars were inserted, giving rise to 10 complications (1.3%). Three unintended laparotomies were required for bowel or bladder injuries (0.4%). Finally, the introduction of the laparoscope was responsible for 11 complications (1.4%); this figure represents 50% of all the complications of this series. Eight intraoperative complications (1%) occurred during the laparoscopic surgery (seven severe bleedings and one ureter injury, but no intestinal lesions); laparotomy was required in six of these cases. Three complications occurred during the postoperative stage: one granulomatous peritonitis after intraabdominal rupture of a dermoid cyst, one incisional hernia, and a fast-resolving cardiac arrhythmia.Conclusions: In our experience, operative gynecological laparoscopy is associated with an acceptable morbidity rate. Moreover, about half of the complications occur during the installation of the laparoscopic procedure, underscoring the usefulness of safety rules. [ABSTRACT FROM AUTHOR]

The reasons for unnecessary ED encounters for rabies vaccination were previous ED discharge instructions to return to the ED (n=6), lack of follow-up instructions at previous ED discharge (n=4), and unclear documentation (n=1). Conclusions Approximately 16% to 48% of ED encounters for rabies PEP are solely for delivery of subsequent rabies vaccine, which may unnecessarily strain ED resources and burden healthcare finances. [Extracted from the article]

Competing Interests: Conflicts of interest The authors report no conflicts of interest relevant to this work.

Purpose: Central venous catheters (CVCs) provide a direct route to the venous circulation but are prone to catheter-related thrombosis (CRT). A known CRT risk factor is a high catheter-to-vein ratio (CVR), or a large catheter diameter with respect to the indwelling vein size. In this study, the CVR's effect on CVC hemodynamics and its impact on CRT is investigated with in vitro and in silico experiments., Methods: An in vitro flow loop is used to characterize the hemodynamics around CVCs using particle image velocimetry. In addition, CRT is investigated using an in vitro flow loop with human blood and clinical catheters. The wall shear rate of flow around the CVC is computed numerically. CVRs of 0.20, 0.33, and 0.49 and Reynolds numbers of 200, 800, and 1300 are evaluated. No flow is used through CVC lumens to model chronic indwelling catheters., Results: Results show CVR ≥ 0.33 promotes platelet-rich clot growth at the device tip and at an increased rate compared to lower CVR cases. A high wall shear rate gradient on the CVC tip and an extended wake distal to the tip exists for higher CVR cases, promoting the aggregation of platelets and subsequent stagnation for clot formation. Further, the combination of the CVR and Reynolds number are crucial to CRT potential, not the CVR alone. Specifically, thrombosis risk is increased with low (stasis driven) and/or high (platelet activation driven) flow conditions, with the CVR and CVC's geometry playing an additional role in promoting fluid mechanic driven thrombus development. A high CVR (≥ 0.33) and high flow condition (≥ 1300) results in the highest risk for clot growth at the tip of the device; other locations of the device are at risk for thrombus development in lower flow conditions, regardless of the CVR. The importance of the device geometry and flow in promoting thrombus and fibrin sheath formation is also shown for the device investigated., Conclusions: This work demonstrates that the CVR, flow, and device geometry affect CRT. For clinical cases with CVR ≥ 0.33 and/or Re ≥ 1300, the device tip may be monitored more consistently for clot formation. Thrombosis risks remain on the entire catheter, regardless of the flow condition, for a CVR = 0.49. Device placement should be chosen carefully with respect to the combination of the Reynolds number and CVR. Further study is needed on the effect of catheterization to confirm these findings., Competing Interests: Declarations. Ethical Approval and Consent to Participate: This study was approved by the Pennsylvania State University Institutional Review Board (Study 00019955). All participants provided written informed consent prior to enrolment in the study. Consent for Publication: All authors approve publication of this work. Competing Interests: KBM has a financial interest in Cranial Devices, Inc, a company which could potentially benefit from the results of this research. The interest has been reviewed and is being managed by the University in accordance with its individual Conflict of Interest policy, for the purpose of maintaining the objectivity of research at The Pennsylvania State University., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Activated partial thromboplastin time (aPTT) and unfractionated heparin (UFH) level via the anti-factor Xa activity assay (anti-Xa) are commonly used assays for UFH monitoring. While discordance between the two assays is common, its impact on critically ill patient outcomes is unclear. This study aimed to compare the incidence of major bleeding events among critically ill patients with discordant aPTT and anti-Xa activity while on UFH, to patients with no discordance. This was a single-center, retrospective cohort study of critically ill adult patients who had simultaneous anti-Xa and aPTT levels while receiving continuous UFH infusion. The primary outcome was the incidence of a major bleeding event up to 24 h after UFH discontinuation. Secondary outcomes included incidence of 30-day thrombosis and hospital length of stay (LOS). Among 264 included patients, 156 patients (59%) had at least one discordant paired level. Patients with discordance had an increased risk of major bleeding events (14% versus 5%; unadjusted risk ratio, 3.0; 95% CI 1.2-7.8; p = 0.01), and increased risk of thrombotic events (4% versus 0%; p = 0.04). Hospital LOS was similar between the two groups (13.8 days versus 11.4 days; p = 0.08). In this cohort of critically ill patients receiving continuous UFH, discordance in aPTT and anti-Xa activity was frequently observed and was associated with an increased risk of major bleeding events. While both assays remain viable monitoring options, evaluating simultaneous levels may aid in the management of critically ill patients. In patients with discordance, an individualized approach balancing bleeding and thrombotic risks should be considered., Competing Interests: Declarations. Competing interests: All authors declare that they have no conflicts of interest to disclose related to this research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The role of beta-blockers in severe, traumatic brain injury (TBI) management is debated. Severe TBI may elicit a surge of catecholamines, which has been associated with increased morbidity and mortality. We hypothesize administering propranolol, a non-selective beta-blocker, within 48 h of TBI will reduce patient mortality within 30 days of injury. The TriNetX database was leveraged to determine if administering a propranolol within 48 h of severe TBI improves outcomes within 30 days of injury., Methods: The TriNetX Research Network was used to form two cohorts using retrospective data from 106,294,356 patient profiles from 9/10/2022, which included patients from years 2022 to 2022. The propranolol-receiving cohort included all patients who received the first-instance diagnosis of severe TBI (defined by a Glascow coma scale score of 3-8) and propranolol within 48 h of injury. The non-propranolol-receiving cohort included all patients with the same diagnosis of severe TBI but did not receive beta-blockers. The primary outcome of interest was mortality at 30 days. Secondary outcomes included gastrostomy tube placement, neurosurgical intervention in the form of craniotomy, craniectomy, burr hole drainage, seizure, and cardiac arrest., Results: After propensity score-matching, 381 patients were identified for both cohorts. At 30 days post-severe TBI, 22.7% (84) of patients from the cohort that received propranolol, and 30.77% (116) from the cohort that did not, were deceased (OR 0.66), 95% CI [0.48, 0.92]), (p 0.01). TBI patients who received propranolol also had lower odds of requiring neurosurgical intervention, experience seizures, and cardiac arrest., Conclusion: The results of this study demonstrate significantly reduced mortality within 30 days of injury and fewer neurosurgical interventions, seizures, and episodes of cardiac arrest in severe TBI patients who received propranolol within 48 h of injury., Competing Interests: Declarations. Ethical approval: We confirm this study adhered to the ethical guidelines of this journal. This study includes data from the TriNetX database. The information in this database is updated daily and includes information regarding patient demographics, diagnoses, medications, and outcomes. This study utilized the TriNetX United States (U.S.) Collaborative Network, which contains information on 86,401,400 patients from 69 academic institutions. The database is federated. Thus, an Institutional Review Board approval for this study has been waived. Consent to participate: This declaration is not applicable. Consent for publication: Authorship requirements have been met and the final manuscript was approved by all authors. Competing interests: The authors declare no competing interests. Submission: This manuscript has not been published elsewhere and is not under consideration by another journal., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: An efficient procedure was reported for the synthesis of novel hybrid dithiazoles 7 and thiazoles 15, in good yields, by applying hydrazonyl chlorides 4 with thiocarbohydrazone derivatives 3 and 12., Methods: The thiazole derivatives were evaluated for their antimicrobial and antioxidant activities., Results: According to the results, thiazoles revealed marked potency as antimicrobial and antioxidant agents. Thus, 7a's DPPH radical scavenging activity was excellent (38.19±0.33 and 14.37±0.4) at concentrations of 2.0 and 1.0 mg/mL, respectively. In addition, compound 3 exhibited activity against all bacterial strains tested, as evidenced by inhibition zones measuring that ranged from 8.5±0.43 mm for E. faecalis to 16.5±0.43 mm for S. mutans., Conclusion: The MIC results showed that compound 3 was effective against E. coli, S. aureus, E. faecalis, P. aeruginosa, and S. mutans at concentrations of 1.0, 1.0, 2.0, 1.0, and 1.0 mg/mL, respectively. Furthermore, molecular docking has shown lower binding energy with different types of interactions at the active sites of Dihydropteroate synthase, Sortase A, LasR, and penicillin-binding protein pockets, indicating that these compounds could inhibit the enzyme and cause promising antimicrobial effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Gliosarcoma is a rare histopathological variant of glioblastoma, but it is unclear whether distinct clinical or molecular features distinguish it from other glioblastomas. The purpose of this study was to characterize common genomic alterations of gliosarcoma, compare them to that of glioblastoma, and correlate them with prognosis., Methods: This was a single-institution, retrospective cohort study of patients seen between 11/1/2017 to 1/28/2024. Clinical and genomic data were obtained from the medical record. Results were validated using data from AACR Project GENIE (v15.1-public)., Results: We identified 87 gliosarcoma patients in the institutional cohort. Compared to a contemporary cohort of 492 glioblastoma, there was no difference in overall survival, though progression free survival was inferior for patients with gliosarcoma (p = 0.01). Several of the most-commonly altered genes in gliosarcoma were more frequently altered than in glioblastoma (NF1, PTEN, TP53), while others were less frequently altered than in glioblastoma (EGFR). CDKN2A/CDKN2B/MTAP alterations were associated with inferior survival on univariate Cox (HR = 5.4, p = 0.023). When pooled with 93 patients from the GENIE cohort, CDKN2A/B (HR = 1.75, p = 0.039), RB1 (HR = 0.51, p = 0.016), LRP1B (p = 0.050, HR = 2.0), and TSC2 (HR = 0.31, p = 0.048) alterations or loss were significantly associated with survival. These effects remained when controlled for age, sex, and cohort of origin with multivariate Cox., Conclusion: Gliosarcoma has a similar overall survival but worse response to treatment and different mutational profile than glioblastoma. CDKN2A/B loss and LRP1B alterations were associated with inferior prognosis, while RB1 or TSC2 alterations were associated with improved outcomes. These findings may have implications for clinical management and therapeutic selection in this patient population., Competing Interests: Declarations. Ethics approval: This study was approved by the Johns Hopkins Institutional Review Board (IRB00442172) on 4/29/2024. Consent to participate: A waiver of the HIPAA Privacy Authorization requirement was granted by the Johns Hopkins Institutional Review Board as part of the study approval process. Consent to Publish: Consent to publish was not obtained from participants. All identifying information has been removed. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: The objectives of this study were to identify the most performed surgical procedures associated with the highest rates of discharge opioid overprescribing and to implement an electronic health record (EHR) alert to reduce discharge opioid overprescribing., Methods: This quality improvement, before-and-after study included patients undergoing one of the identified target procedures-laparoscopic cholecystectomy, unilateral open inguinal hernia repair, and laparoscopic appendectomy-at an academic medical center. The alert notified providers when the prescribed opioid quantity exceeded guideline recommendations. The preimplementation cohort included surgical encounters from January 2020 to December 2021. The EHR alert was implemented in May 2022 following provider education via email and in-person presentations. The postimplementation cohort included surgical encounters from May to August 2022. The primary outcome was the proportion of patients with a discharge opioid supply exceeding guideline recommendations (overprescribing)., Results: A total of 1,478 patients were included in the preimplementation cohort, and 141 patients were included in the postimplementation cohort. The proportion of patients with discharge opioid overprescribing decreased from 48% in the preimplementation cohort to 3% in the postimplementation cohort, with an unadjusted absolute reduction of 45% (95% confidence interval, 41% to 49%; P < 0.001) and an adjusted odds ratio of 0.03 (95% confidence interval, 0.01 to 0.08; P < 0.001). Among patients who received opioids, the mean (SD) opioid supply at discharge decreased from 92 (43) oral morphine milligram equivalents (MME) (before implementation) to 57 (20) MME (after implementation) (P < 0.001). The proportion of patients who received additional opioid prescriptions within 1 to 14 days following hospital discharge did not change (P = 0.76)., Conclusion: Implementation of an EHR alert along with provider education can reduce discharge opioid overprescribing following general surgery., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Tissue biofabrication mimicking organ-specific architecture and function requires physiologically-relevant cell densities. Bioprinting using spheroids can achieve this, but is limited due to the lack of practical, scalable techniques. This study presents HITS-Bio (High-throughput Integrated Tissue Fabrication System for Bioprinting), a multiarray bioprinting technique for rapidly positioning multiple spheroids simultaneously using a digitally-controlled nozzle array (DCNA). HITS-Bio achieves an unprecedented speed, ten times faster compared to existing techniques while maintaining high cell viability ( > 90%). The utility of HITS-Bio was exemplified in multiple applications, including intraoperative bioprinting with microRNA transfected human adipose-derived stem cell spheroids for calvarial bone regeneration ( ~ 30 mm 3 ) in a rat model achieving a near-complete defect closure (bone coverage area of ~ 91% in 3 weeks and ~96% in 6 weeks). Additionally, the successful fabrication of scalable cartilage constructs (1 cm 3 ) containing ~600 chondrogenic spheroids highlights its high-throughput efficiency (under 40 min per construct) and potential for repairing volumetric defects., Competing Interests: Competing interests: I.T.O. has an equity stake in Biolife4D and is a member of the scientific advisory board for Biolife4D and Healshape. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Background: Opioids are important medications that are used to control postoperative pain. The enhanced recovery after surgery (ERAS) program has reduced opioid use after surgery. In a surgical practice with a robust ERAS program, we wanted to determine if there was a relationship between in-hospital opioid use and postoperative complications., Methods: We performed a retrospective nested case-control study of patients who underwent thoracic surgical intervention at the Houston Methodist Hospital (HMH) between 11/2020 and 11/2021 from the thoracic surgery database with hospital morphine milligram equivalent (MME) information, comparing patients who did and did not experience postoperative complications. We determined the total MME and average daily MME patients received during their hospitalization. We performed receiver operating characteristic (ROC) curve analysis with the Youden index to determine the optimal cutoff points for total MME and daily MME. We performed univariable and multivariable logistic regression analyses of the factors associated with postoperative complications., Results: A total of 419 patients were included who were mostly female (59%) and white (75%). Most patients underwent either foregut surgery (52%) or lung surgery (25%). Of the patients, 160 (38%) were on home pain medication before surgery, and 52 (12.4%) were on opioid pain medication before surgery. The median total MME during hospitalization was 73 mg, with a median average daily MME of 30 mg. There were 37 patients (8.8%) who experienced postoperative complications. Patients who had complications had a significantly higher median total MME of 135 [interquartile range (IQR) 73.0, 743.0] vs. 70 (IQR 45, 108) mg; P<0.001. Patients with a total MME ≥241 mg were more than four times more likely to have postoperative complications than those with an MME <241 mg (31.0% vs. 5.3%; P<0.001). Patients who received daily MME ≥60 mg had significantly more postoperative complications (20.0% vs. 6.8%; P=0.001). Multivariate logistic regression analysis showed that Hispanic ethnicity [odds ratio (OR) 4.33; 95% confidence interval (CI): 1.63, 11.51; P=0.003], operation duration (OR 1.01; 95% CI: 1.00, 1.01; P=0.01), and total MME (OR 1.001; 95% CI: 1.00, 1.002; P<0.001) were associated with postoperative complications., Conclusions: Hospital opioid use was associated with complications after thoracic surgical procedures. The amount of opioid medication received during hospitalization was an independent risk factor for postoperative complications in our patient population. Efforts to decrease the amount of opioid medication used with multimodal non-opioid medications may help improve surgical outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-825/coif). M.P.K. serves as an unpaid editorial board member of Journal of Thoracic Disease from September 2022 to August 2024. M.P.K. received royalties or licenses for VATS lobectomy video from Medtronic, honoria for teaching other surgeons on the use of technology from Medtronic and Intuitive Surgical. He has also consulted for Olympus. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Introduction: The goal of surgical management in pediatric low-grade gliomas (pLGGs) is gross total resection (GTR), as it is considered curative with favorable long-term outcomes. Achieving GTR can be challenging in the setting of eloquent-region gliomas, in which resection may increase risk of neurological deficits. Awake craniotomy (AC) with intraoperative neurofunctional mapping (IONM) offers a promising approach to achieve maximal resection while preserving neurological function. However, its adoption in pediatric cases has been hindered, and barriers to its adoption have not previously been elucidated., Findings: This review includes two complementary investigations. First, a survey study was conducted querying pediatric neurosurgeons on their perceived barriers to the procedure in children with pLGG. Next, these critical barriers were analyzed in the context of existing literature. These barriers included the lack of standardized IONM techniques for children, inadequate surgical and anesthesia experience, concerns regarding increased complication risks, doubts about children's ability to tolerate the procedure, and perceived non-indications due to alternative monitoring tools., Conclusion: Efforts to overcome these barriers include standardizing IONM protocols, refining anesthesia management, enhancing patient preparation strategies, and challenging entrenched beliefs about pediatric AC. Collaborative interdisciplinary efforts and further studies are needed to establish safety guidelines and broaden the application of AC, ultimately improving outcomes for children with pLGG., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Perioperative management of antithrombotic therapy is a necessary preprocedural consideration for patients prescribed direct oral anticoagulants (DOACs), vitamin K antagonists, or antiplatelet medications. There is a lack of evidence-based guidelines to help inform decision-making in managing antiplatelet and anticoagulation medications in the perioperative period around brain tumor resection. The objective of this study was to provide an example of the heterogeneity in practice and raise awareness for the need to create standardized guidelines for managing these medications., Methods: A survey was sent to a list of over 800 international neurosurgeons who are members of the Neurosurgery Research Listserv. The survey comprised 70 questions assessing individual practices for managing thromboprophylaxis, antiplatelet medications, and anticoagulation in the perioperative period. The survey was sent via e-mail invitation between March 2021 and June 2021., Results: A total of 72 surgeons responded to the survey. There was no difference in medication management preoperatively or postoperatively when comparing intra- and extra-axial tumor resections. Cessation of antiplatelet medications varied between 3 and 11 days while restart varied between 1 and 14 days. Preoperative management of vitamin K antagonists varied between indication for use (P < 0.001) while DOAC management did not. In our group of respondents, 90% started heparin products within 5 days of surgery, while the same fraction restarted DOAC within 14 days., Conclusions: Respondents demonstrated significant heterogeneity in their perioperative management of antiplatelet and anticoagulation medication in brain tumor resection. This may lead to an unacceptable level of heterogeneity in practice that has the potential to cause patient harm due to errors in medication management., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Astrocytoma is the most common adult brain tumor, with glioblastoma being the deadliest neuro-related malignancy. Despite advances in oncology, the prognosis for astrocytoma, especially glioblastoma, remains poor, and tracking disease progression is challenging due to a lack of robust biomarkers. Genetic biomarkers, including microRNAs, cell-free DNA, circulating tumor DNA, circular RNA, and long noncoding RNA, can serve as potential diagnostic and therapeutic targets. In this review, we examine the existing literature, analyzing the various less established liquid and tumor genetic biomarkers and their potential to act as diagnostic, prognostic, and therapeutic targets. We highlight the clinical challenges and limitations in implementing liquid biopsy strategies in clinical practice. The article discusses the potential of liquid biopsies as valuable tools for personalized astrocytoma management while emphasizing the need for standardized protocols and further advancements to establish their clinical utility and therapeutic application., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Common peroneal (fibular) neuropathy is the most common mononeuropathy of the lower extremity. Despite this, there are surprisingly few studies on the topic, and a knowledge gap remains in the literature. As one attempts to address this knowledge gap, a core outcome set (COS) is needed to guide the planning phases of future studies to allow synthesis and comparability of these studies. The objective of this study was to develop the COS-common peroneal neuropathy (CoPe) using a modified Delphi approach., Methods: A 5-stage approach was used to develop the COS-CoPe: 1) stage 1, consortium development; 2) stage 2, a literature review to identify potential outcome measures; 3) stage 3, a Delphi survey to develop consensus on outcomes for inclusion; 4) stage 4, a Delphi survey to develop definitions; and 5) stage 5, a consensus meeting to finalize COS and definitions. The study followed the COS-STAndards for Development (COS-STAD) recommendations., Results: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-CoPe consisted of 31 data points/outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months. The consensus optimal time points for assessment were preoperatively and 3, 6, 12, and 24 months postoperatively., Conclusions: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-CoPe should serve as a minimum set of data that should be collected in all future neurosurgical studies on common peroneal neuropathy. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Purpose: Tethered spinal cord syndrome (TCS) is characterized by cutaneous attachments on the filum terminale that stretch the spinal cord, leading to musculoskeletal and urogenital sequelae. While the neurocutaneous associations with TCS remain undefined, a recent study reports a high incidence of TCS among a pediatric neurofibromatosis (NF) cohort. This present study utilizes a population-level database to estimate TCS incidence among pediatric patients with neurofibromatosis types 1 and 2 (NF1, NF2)., Methods: The TriNetX Research Network was queried to identify patients diagnosed with NF and/or TCS before the age of 21. Symptomatic TCS requiring surgical intervention was identified using corresponding procedural codes within 12 months following TCS diagnosis. Odds ratios (OR) were calculated to measure the associations of NF1/NF2 with TCS., Results: 19,426 pediatric NF patients were evaluated (NF1: 18,383, NF2: 1042). The average ages of TCS diagnosis among NF1, NF2, and non-NF patients were 12, 16, and 9 years, respectively. The incidence of TCS was 1.2% in NF1 patients and 7.3% in NF2 patients, compared to 0.074% in the general population. The associations of NF incidence with TCS were significantly increased in both NF1 (OR 16.42; 14.38-18.76) and NF2 (OR 105.58; 83.56-133.40) patients compared to the general population. Symptomatic TCS requiring surgical intervention was not significantly associated with NF1/NF2 patients compared to the general TCS population., Conclusion: This analysis demonstrates a high incidence of TCS but delayed intervention in pediatric NF patients. Considering TCS counseling, spinal MRI, and earlier intervention may be warranted for NF patients experiencing musculoskeletal symptomatology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Traumatic brain injury (TBI) can cause rapid brain inflammation. There is debate over the safety and efficacy of anti-inflammatory agents in its treatment. With a particular focus on cyclooxygenase 2 (COX2) selective inhibition, we sought to determine the impact of celecoxib versus no celecoxib treatment on outcomes in patients with TBI and compare these with outcomes associated with nonselective COX inhibition (ibuprofen) and corticosteroid (dexamethasone) treatment., Methods: This retrospective cohort study used TriNetX, a large publicly available global health research network, to gather clinical data extracted from the electronic medical records. Using International Classification of Diseases, Tenth Revision and pharmacy codes, we identified patients with TBI who were and were not treated with celecoxib, ibuprofen, and dexamethasone. Analysis was performed on propensity-matched and unmatched cohorts, which were matched on demographics, comorbidities, and neurological injuries. Our primary end point was 1-year survival. Secondary end points were ventilator and tracheostomy dependence, gastrostomy tube placement, seizures, and craniotomy., Results: After propensity score matching, a total of 1443 patients were identified in both the celecoxib and no celecoxib cohorts. Ninety-two (6.4%) patients in the celecoxib cohort died within 1 year following TBI versus 145 (10.0%) in the no celecoxib cohort (odds ratio 0.61; 95% confidence interval 0.46-0.80; p = 0.0003). The 1-year survival rate was 96.1% in the celecoxib cohort versus 93.1% in the no celecoxib cohort (p < 0.0001). At the end of the 1-year period, celecoxib was associated with significantly lower gastrostomy tube dependence (p = 0.017), seizure activity (p = 0.027), and myocardial infarction (p = 0.021) compared with the control cohort. Ibuprofen was also associated with higher 1-year survival probability and lower rates of post-TBI complications. Dexamethasone was broadly associated with higher morbidity but was associated with higher 1-year survival probability compared with the no dexamethasone cohort., Conclusions: Early celecoxib and ibuprofen use within 5 days post TBI was associated with higher 1-year survival probabilities and fewer complications. With emerging yet controversial preclinical evidence to suggest that COX inhibition improves TBI outcomes, this population-level study offers suggestive support for these drugs' clinical benefit, which should be pursued in prospective clinical studies., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

An in silico study is performed to investigate fluid dynamic effects of central venous catheter (CVC) placement within patient-specific cavo-atrial junctions. Prior studies show the CVC infusing a liquid, but this study focuses on the placement without any liquid emerging from the CVC. A 7 or 15-French double-lumen CVC is placed virtually in two patient-specific models; the CVC tip location is altered to understand its effect on the venous flow field. Results show that the CVC impact is trivial on flow in the superior vena cava when the catheter-to-vein ratio ranges from 0.15 to 0.33. Results further demonstrate that when the CVC tip is directly in the right atrium, flow vortices in the right atrium result in elevated wall shear stress near the tip hole. A recirculation region characterizes a spatially variable flow field inside the CVC side hole. Furthermore, flow stagnation is present near the internal side hole corners but an elevated wall shear stress near the curvature of the side hole's exit. These results suggest that optimal CVC tip location is within the superior vena cava, so as to lower the potential for platelet activation due to elevated shear stresses and that CVC geometry and location depth in the central vein significantly influences the local CVC fluid dynamics. A thrombosis model also shows thrombus formation at the side hole and tip hole. After modifying the catheter design, the hemodynamics change, which alter thrombus formation. Future studies are warranted to study CVC design and placement location in an effort to minimize CVC-induced thrombosis incidence., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objective Spinal fusions are gaining popularity as a means of treating spinal deformity and instability from a range of pathologies. The prevalence of glucocorticoid use has also increased in recent decades, and their systemic effects are well-documented. Although commonly used in the preoperative period, the effects of steroids on outcomes among patients undergoing spinal fusions are inadequately described. This study compares the odds of developing complications among patients who underwent single-level lumbar fusions with and without preoperative glucocorticoid use in hopes of establishing more evidence-based parameters for guiding preoperative steroid use. Methods The TriNetX multi-institutional electronic health record database was used to perform a retrospective, propensity score-matched analysis of clinical outcomes of two cohorts of patients who underwent posterior or posterolateral single-level lumbar fusions with and without interbody fusion, those who used glucocorticoids for at least one week within a year of fusion and those who did not. The outcomes of interest were examined within 30 days of the operation and included death, reoperation, deep or superficial surgical site infection (SSI), pneumonia, reintubation, ventilator dependence, tracheostomy, acute kidney injury (AKI), renal insufficiency, pulmonary embolism (PE) or deep venous thrombosis (DVT), urinary tract infection (UTI), emergency department (ED) visit, sepsis, and myocardial infarction (MI). Results The odds of developing pneumonia within 30 days of spinal fusion in the cohort that used glucocorticoids within one year of operation compared to the cohort without glucocorticoid use was 0.67 (p≤0.001, 95% CI: 0.59-0.69). The odds of requiring a tracheostomy within 30 days of spinal fusion in the cohort that used glucocorticoids within one year of operation compared to the cohort without glucocorticoid use was 0.39 (p≤0.001, 95% CI: 0.26-0.60). The odds of reoperation, deep and superficial SSI, and ED visits within 30 days of operation were significantly higher for the same glucocorticoid-receiving cohort, with odds ratios of 1.4 (p=0.003, 95% CI: 1.11-1.65), 1.86 (p≤0.001, 95% CI: 1.31-2.63), 2.28 (p≤0.001, 95% CI: 1.57-3.31), and 1.25 (p≤0.001, 95% CI: 1.17-1.33), respectively. After propensity score-matching, there was no significant difference between the odds of death, DVT, PE, MI, UTI, AKI, sepsis, reintubation, and ventilator dependence between the two cohorts. Conclusion In support of much of the current literature regarding preoperative glucocorticoid use and rates of complications, patients who underwent a single-level lumbar fusion and have used glucocorticoids for at least a week within a year of operation experienced significantly higher odds of reoperation, deep and superficial SSI, and ED visits. However, these patients using glucocorticoids were also found to have lower odds of developing pneumonia, renal insufficiency, and tracheostomy requirement than those who did not use steroids within a year of surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Stoltzfus et al.)

This review article examines the synthetic pathways for triazolothiadiazine derivatives, such as triazolo[3,4- b ]thiadiazines, triazolo[5,1- b ]thiadiazines, and triazolo[4,3- c ]thiadiazines, originating from triazole derivatives, thiadiazine derivatives, or thiocarbohydrazide. The triazolothiadiazine derivatives exhibit several biological actions, including antibacterial, anticancer, antiviral, antiproliferative, analgesic, anti-inflammatory, and antioxidant properties. The review article aims to assist researchers in creating new biologically active compounds for designing target-oriented triazolothiadiazine-based medicines to treat multifunctional disorders.

Objective: When considering traumatic brachial plexus and upper extremity nerve injuries, iatrogenic nerve injuries, and nontraumatic nerve injuries, brachial plexus and upper extremity nerve injuries are commonly encountered in clinical practice. Despite this, data synthesis and comparison of available studies are difficult. This is at least in part due to the lack of standardization in reporting and a lack of a core outcome set (COS). Thus, there is a need for a COS for adult brachial plexus and upper extremity nerve injuries (COS-BPUE). The objective of this study was to develop a COS-BPUE using a modified Delphi approach., Methods: A 5-stage approach was used to develop the COS-BPUE: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations., Results: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-BPUE consisted of 36 data points/outcomes covering demographic, diagnostic, patient-reported outcome, motor/sensory outcome, and complication domains. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, 12, and 24 months postoperatively., Conclusions: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-BPUE should serve as a minimum set of data that should be collected in all future neurosurgical studies on adult brachial plexus and upper extremity nerve injuries. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Hay-holes are a design feature in many traditionally built barns that serve as a portal through which stored hay is passed to the lower level where animals are fed. Unfortunately, children sometimes fall through the hay-hole to the concrete or packed earth below. Available data on the frequency and types of hay-hole injuries is limited. The purpose of this study was to better characterize the resultant injuries and identify prognostic factors that predict outcomes from them. We performed a retrospective review of 53 children admitted to the Penn State Hershey Children's Hospital at the Penn State Hershey Medical Center with injuries due to a fall through a hay-hole over 15 years. Compared to urban trauma, hay-hole falls more frequently involve younger children and craniofacial injuries. Although they may result in significant injuries, they are rarely fatal. Greater fall height is associated with longer length of stay (LOS) but not with a greater frequency of intubation, intracranial hemorrhage, or skull fracture. A re-examination of barn design may help to reduce the frequency of this injury type., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yang et al.)

Background: Delays or failure to complete a dermatologic referral may affect health care outcomes. Factors associated with these delays remain understudied., Objective: This study investigated socioeconomic and demographic factors associated with delays or failure to complete dermatology referrals and potential impact on surgical outcomes., Methods: A retrospective chart review was performed for 400 patients internally referred to an academic dermatology center from 19 primary-care clinics from July 2018 to June 2019. Only patients referred after an in-person primary-care visit in which the provider documented a specific concerning lesion were included. Multivariate analyses were performed to explore variables associated with delays or failure to complete dermatology referrals., Results: Patients were more likely to complete their referral if they had a personal history (adjusted odds ratio [aOR] = 7.843, 95% CI 1.383-14.304) or family history (aOR = 11.307, 95% CI 2.344-20.27) of skin cancer. Patients were more likely to delay referral completion past 30 days if they were ages 18 to 34 (aOR = 6.665, 95% CI 1.285-12.044) and less likely to delay referral past 30 days if they had a previous history of skin cancer (aOR = 0.531, 95% CI 0.181-0.882)., Limitations: Single institution, retrospective study, limited surgical patients., Conclusion: Understanding factors associated with delays in dermatology referral completion can help identify at-risk patient populations., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Congenital hydrocephalus is a significant challenge in neurosurgery, particularly in resource-limited settings. This study focuses on the congenital hydrocephalus in Brazil, a developing country, over the past 13 years., Methods: This study is a retrospective analysis of congenital hydrocephalus treatment and outcomes using data records on DATASUS from January 2008 to July 2021. Demographics, cost of hospitalizations, amount paid to professionals, mortality, and mean length of stay (LOS) were analyzed. Statistical analysis was conducted to determine significant associations between these indicators and pediatric hydrocephalus., Results: DATASUS recorded 8493 cases of congenital hydrocephalus in the studied period, with a prevalence of 24.28 per 100,000 newborns, mostly linked to spina bifida. Congenital hydrocephalus caused 60.83 ± 13.98 neonatal deaths per year, with the highest rate among 32-36 weeks gestational age. Acquired hydrocephalus led to 1063 infant deaths, whereas congenital hydrocephalus resulted in 3122 deaths, with no clear trend by the years. White infants had the highest mortality. A total of 33,184 shunt procedures were performed, with an average cost of $715.37 per procedure. The mortality model showed no significant effects of cost or professionals' salary, but a significant effect of LOS on hospitalization costs was observed., Conclusions: Pediatric hydrocephalus in Brazil's public health system is a significant burden. Congenital hydrocephalus prevalence and mortality emphasize the need for early diagnosis and treatment. Early diagnosis, prenatal care, and adequate resources are crucial. This study offers insights into congenital hydrocephalus, highlighting challenges and future directions for improved care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown., Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model., Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.3 SEM1-DLX5-DLX6 locus, and their combination conferred over 7-fold increased risk of cNCS. The top variants were replicated in an independent cohort and showed pleiotropic effects on brain and facial morphology and bone mineral density. Fine mapping of 7q21.3 identified a craniofacial transcriptional enhancer (eDlx36) within the linkage region of the top variant (rs4727341; odds ratio [95% confidence interval], 0.48[0.39-0.59]; P = 1.2E-12) that was located in SEM1 intron and enriched in 4 rare risk variants. In zebrafish, the activity of the transfected human eDlx36 enhancer was observed in the frontonasal prominence and calvaria during skull development and was reduced when the 4 rare risk variants were introduced into the sequence., Conclusion: Our findings support a polygenic nature of cNCS risk and functional role of craniofacial enhancers in cNCS susceptibility with potential broader implications for bone health., Competing Interests: Conflict of Interest The authors declare no competing interests in relation to the work described.

Objective: Carpal tunnel syndrome (CTS) presents bilaterally in nearly 60%-70% of affected patients. Bilateral carpal tunnel release (CTR) can be performed in a staged or simultaneous fashion. There remains a limited understanding of the optimal preoperative factors to use for patient selection when determining simultaneous versus staged bilateral CTR. Moreover, it is unclear how these factors influence postoperative outcomes. In this study, the authors aimed to identify and compare preoperative comorbidities and postoperative outcomes in patients who had undergone simultaneous versus staged open and endoscopic bilateral CTR., Methods: The authors performed a retrospective analysis of data collected from the TriNetX database. Patients with bilateral CTS who had been treated from February 1, 2002, to February 1, 2022, were dichotomized by their bilateral release approach: simultaneous or staged within 3 months. The resulting groups were analyzed separately by open versus endoscopic techniques. Next, cohorts were analyzed for preoperative comorbidities to identify possible factors for surgical determination. Then, they were propensity score matched on demographics and comorbidities. Postoperative outcomes within 6 months of surgery were measured with and without matching., Results: After matching, 9286 and 3709 patients remained in the open and endoscopic groups, respectively. Those who had undergone staged surgeries via an open or endoscopic approach had more preoperative comorbidities. After matching, staged open release was associated with significantly higher rates of postprocedural care, hand/joint pain, limb pain, trigger finger, and upper respiratory tract infections. Simultaneous open release was associated with higher rates of emergency room visits. Staged endoscopic release was associated with significantly higher rates of postprocedural care, limb pain, and trigger finger. No significant outcomes were favored in the simultaneous endoscopic group., Conclusions: Before matching, patients who had undergone staged CTR had significantly higher rates of preoperative medical comorbidities compared with patients in the simultaneous CTR group. Moreover, staged CTR was significantly associated with higher rates of postoperative complications. After matching on demographics and comorbidities, staged CTR was still associated with higher rates of postoperative complications, suggesting that preoperative comorbidities do not influence postoperative outcome. Further prospective studies could be used to validate these results and provide new findings for the management and treatment of these groups.

Background: Despite the importance of patient satisfaction in ensuring high-quality care, studies investigating patient satisfaction in Mohs micrographic surgery (MMS) are limited., Objective: We investigated the factors associated with patient satisfaction in MMS for nonmelanoma skin cancer and how patient satisfaction changes in the postoperative period., Methods: In this prospective cohort study including 100 patients, patient satisfaction surveys were administered at the time of surgery and at 3 months postsurgery. Sociodemographic characteristics, medical history, and surgical parameters were collected by chart review. Univariate linear and logistic regression models were created to examine these relationships., Results: Decreased satisfaction was observed in patients requiring 3 or more MMS stages both at the time of surgery (P = .047) and at 3 months post-surgery (P = .0244). Patients with morning procedures ending after 1:00 pm had decreased satisfaction at the time of surgery (P = .019). A decrease in patient satisfaction between the time of surgery and 3 months postsurgery was observed in patients with surgical sites on the extremities (P = .036), larger preoperative lesion sizes (P = .012), and larger defect sizes (P = .033)., Limitations: Single-institution data, self-selection bias, and recall bias., Conclusion: Patient satisfaction with MMS is impacted by numerous factors and remains dynamic over time., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) used for osteoarthritis (OA) in primary care may cause gastrointestinal or renal injury. This study estimated adherence to two quality indicators (QIs) to optimize NSAID safety: add proton pump inhibitors (PPI) to NSAIDs for patients with gastrointestinal (GI) risk (QI #1 NSAID-PPI) and avoid oral NSAIDs in chronic kidney disease (CKD) stage G4 or G5 (QI #2 NSAID-CKD)., Methods: This retrospective study included index primary care clinic visits for knee OA at our health system in 2019. The validation cohort consisted of a random sample of 60 patients. The remainder were included in the expanded cohort. Analysis of structured data extracts was validated against chart review of clinic visit notes (validation cohort) and estimated QI adherence (expanded cohort)., Results: Among 60 patients in the validation cohort, analysis of data extracts was validated against chart review for QI #1 NSAID-PPI (100% sensitivity and 91% specificity) and QI #2 NSAID-CKD (100% accuracy). Among 335 patients in the expanded cohort, 44% used NSAIDs, 27% used PPIs, 73% had elevated GI risk, and only 2% had CKD stage 4 or 5. Twenty-one percent used NSAIDs and had elevated GI risk but were not using PPIs. Therefore, adherence to QI #1 NSAID-PPI was 79% (95% CI, 74-83%). No patients with CKD stage 4 or 5 used NSAIDs. Therefore, adherence to QI #2 NSAID-CKD was 100%., Conclusion: A substantial proportion of knee OA patients with GI risk factors did not receive PPI with NSAID therapy during primary care visits., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: An epidural steroid injection (ESI) is used to treat a number of morbid central nervous system pathologies and is considered a reasonably safe procedure. This study aimed to determine the relative infection risk after spinal surgery by comparing outcomes in spinal surgery patients who received an ESI shortly prior to the surgery against those who did not receive an ESI shortly prior to the surgery., Methods: The present study is a retrospective cohort study using a multi-institutional healthcare database, TriNetX, to collect data on patients who received spinal surgery with and without having had ESIs six months before surgery. Two cohorts were generated: Cohort 1 included patients who had received an ESI in the six months prior to spinal surgery, and cohort 2 included patients who did not have an ESI in the six months prior to spinal surgery. The patients in cohort 2 had propensity scores matched 1:1 to those in cohort 1 using common baseline demographics, comorbidities and spinal procedure indications. The spinal procedures and surgeries considered for the analysis included open procedures for any purpose, including exploration, decompression, resection, revision or biopsy. Multiple outcomes were compared across these two cohorts in the three months following the spinal procedure/surgery, including the occurrence of death, surgical site infection, epidural and/or spinal abscess, and dural tear., Results: An ESI in the six months prior to spinal surgery was associated with a significant decrease in the likelihood epidural/spinal abscess in the three months after surgery. There was no change in mortality, wound infection or identification of dural tear in the three months after spinal surgery for those who received an ESI six months before spinal surgery., Conclusion: This data suggests that epidural steroid injections' anti-inflammatory effects provide benefits before surgery beyond symptomatic relief. Given that the degeneration of spinal pathologies is typically advanced rather than corrected by the body's inflammatory response, it is likely that preventing hyperactivation of the body's immune system in the months preceding surgical intervention, a traumatic insult, is protective compared to no intervention and, importantly, without major adverse effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kozak et al.)

Objective: Ulnar neuropathy at the elbow (UNE) is common, affecting 1%-6% of the population. Despite this, there remains a lack of consensus regarding optimal treatment. This is primarily due to the difficulty one encounters when trying to assess the literature. Outcomes are inconsistently reported, which makes comparing studies or developing meta-analyses difficult or even impossible. Thus, there is a need for a core outcome set (COS) for UNE (COS-UNE) to help address this problem. The objective of this study was to utilize a modified Delphi method to develop COS-UNE., Methods: A 5-stage approach was utilized to develop COS-UNE: stage 1, consortium development; 2, literature review to identify potential outcome measures; 3, Delphi survey to develop consensus on outcomes for inclusion; 4, Delphi survey to develop definitions; and 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations., Results: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 21 participants, all neurological surgeons representing 11 countries. The final COS-UNE consisted of 22 data points/outcomes covering the domains of demographic characteristics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 6 months, with the consensus optimal timepoints for assessment identified as preoperatively and 3, 6, and 12 months postoperatively., Conclusions: The authors identified consensus data points/outcomes and also provided definitions and specific scales to be utilized to help ensure that clinicians are consistent in their reporting across studies on UNE. This COS should serve as a minimum set of data to be collected in all future neurosurgical studies on UNE. The authors hope that clinicians evaluating ulnar neuropathy will incorporate this COS into routine practice and that future studies will consider this COS in the design phase.

Objective Lumbar puncture (LP) is a diagnostic procedure that accesses the spinal subarachnoid space to measure the opening pressure of the cerebrospinal fluid (CSF) and obtain samples of CSF for analysis. Although commonly performed, LPs are associated with the risk of morbidity and mortality. In addition, thrombocytopenia is thought to increase the risk of LP complications, particularly spinal bleeds. This study compares rates of complications among patients who received LPs with and without thrombocytopenia in hopes of establishing more evidence-based platelet thresholds for an LP. Methods The TriNetX multi-institutional electronic health record database was used to perform a retrospective propensity score-matched analysis of clinical outcomes of two cohorts of patients who underwent LPs - those with thrombocytopenia (defined as a platelet level of 10,000-50,000 platelets {plts}/μL) and those without thrombocytopenia. The outcomes of interest were the new occurrence of subdural hematoma, epidural hematoma, subarachnoid hemorrhage, receipt of a blood patch, new onset of paralysis, and requirement of spinal decompression. Results The risk of developing a spinal bleed following an LP was 1.496% (42 of 2,808) for the cohort with thrombocytopenia versus 1.09% (31 of 2,843) for the cohort without thrombocytopenia. The risk difference, risk ratio, and odds ratio of patients from these two cohorts experiencing a spinal bleed following an LP were insignificant at 0.05. The risk of receiving a blood patch following an LP was 7.844% for those with thrombocytopenia compared to 1.421% for those without thrombocytopenia. The odds ratio of receiving a blood patch between the two cohorts was 5.906, significant to the 0.05 level (95% CI: 4.213-8.279). There was no significant difference in the cohorts' risk of developing paralysis or requiring spinal decompression following an LP. Conclusion In support of recent findings against conventional platelet count thresholds prior to LP, it was observed in the present study that the incidence of post-LP spinal bleeding in the 30 days after LP is not associated with platelet counts below the guideline threshold of 50,000 plts/μL. Patients with thrombocytopenia are also not significantly more likely to require spinal decompression or develop new onset paralysis. However, thrombocytopenia is associated with a significantly increased likelihood of receiving a blood patch following an LP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kozak et al.)

Objective: To evaluate the impact of a quality improvement bundle on opioid discharge prescribing following thyroidectomy and parathyroidectomy., Methods: This before-and-after study included patients undergoing thyroidectomy or parathyroidectomy at an academic medical center. The quality improvement bundle included a patient education flyer, electronic health record order sets with multimodal analgesia regimens, and provider education. The preimplementation cohort included patients treated from January 2018 to December 2019. The postimplementation cohort included patients treated from June 2021 to August 2021. The primary outcome was the proportion of patients who received new opioid discharge prescriptions., Results: A total of 160 patients were included in the preimplementation cohort, and the first 80 patients treated after bundle implementation were included in the postimplementation cohort. Patients receiving new opioid discharge prescriptions decreased from 80% (128/160) in the preimplementation cohort to 35% (28/80) in the postimplementation cohort with an unadjusted absolute reduction of 45% (95% CI, 33%-57%; P < .001; number needed to treat = 3) and an adjusted odds ratio (OR) of 0.08 (95% CI, 0.04-0.19; P < .001). The bundle was associated with reductions in opioid discharge prescriptions that exceeded 112.5 oral morphine milligram equivalents (33% pre- vs 10% postimplementation; adjusted OR, 0.20; P = .001) or 5 days of therapy (17% pre- vs 6% postimplementation; adjusted OR, 0.34; P = .049)., Discussion: Implementation of a pain management quality improvement bundle reduced opioid discharge prescribing following thyroidectomy and parathyroidectomy., Implications for Practice: Unnecessary opioid prescriptions generate unused opioids in patients' homes that can lead to opioid misuse. We believe that this bundle reduced the risk for opioid misuse in our community., Registration: The study was registered at ClinicalTrials.gov (NCT04955444) before implementation., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Development of valid and feasible quality indicators (QIs) is needed to track quality initiatives for osteoarthritis pain management in primary care settings., Methods: Literature search identified published guidelines that were reviewed for QI extraction. A panel of 14 experts was assembled, including primary care physicians, rheumatologists, orthopedic surgeons, pain specialists, and outcomes research pharmacists. A screening survey excluded QIs that cannot be reliably extracted from the electronic health record or that are irrelevant for osteoarthritis in primary care settings. A validity screening survey used a 9-point Likert scale to rate the validity of each QI based on predefined criteria. During expert panel discussions, stakeholders revised QI wording, added new QIs, and voted to include or exclude each QI. A priority survey used a 9-point Likert scale to prioritize the included QIs., Results: Literature search identified 520 references published from January 2015 to March 2021 and 4 additional guidelines from professional/governmental websites. The study included 41 guidelines. Extraction of 741 recommendations yielded 115 candidate QIs. Feasibility screening excluded 28 QIs. Validity screening and expert panel discussion excluded 73 QIs and added 1 QI. The final set of 15 prioritized QIs focused on pain management safety, education, weight-management, psychological wellbeing, optimizing first-line medications, referral, and imaging., Conclusion: This multi-disciplinary expert panel established consensus on QIs for osteoarthritis pain management in primary care settings by combining scientific evidence with expert opinion. The resulting list of 15 prioritized, valid, and feasible QIs can be used to track quality initiatives for osteoarthritis pain management., (© 2023. The Author(s).)

There are a variety of surgical approaches to lesions around the sciatic notch. Historically, peripheral nerve surgeons prefer an infragluteal approach involving a large incision with reflection of the gluteus maximus to better visualize the operative field. This approach was imperative when lesion localization was imprecise. Comparatively, orthopedic surgeons prefer a muscle-splitting, transgluteal approach to operate on the static structures of the posterior hip. The transgluteal approach is significantly less morbid, allowing for same-day discharge and less extensive rehab given preservation of the gluteal muscle. In this article we describe the use of dynamic ultrasound imaging to localize and aid in the resection of three unique tumors around the sciatic notch using a minimally invasive, tissue-sparing, transgluteal technique. We offer a comprehensive description of the benefits, anatomic considerations, and nuances of using a transgluteal approach for the resection of lesions at the sciatic notch., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bailey et al.)

There is a pressing clinical need for minimally invasive liquid biopsies to supplement imaging in the treatment of glioblastoma. Diagnostic imaging is often difficult to interpret and the medical community is divided on distinguishing among complete response, partial response, stable disease, and progressive disease. A minimally invasive liquid biopsy would supplement imaging and clinical findings and has the capacity to be helpful in several ways: 1) diagnosis, 2) selection of patients for specific treatments, 3) tracking of treatment response, and 4) prognostic value. The liquid biome is the combination of biological fluids including blood, urine, and cerebrospinal fluid that contain small amounts of tumor cells, DNA/RNA coding material, peptides, and metabolites. Within the liquid biome, 2 broad categories of biomarkers can exist: tumor-derived, which can be directly traced to the tumor, and tumor-associated, which can be traced back to the response of the body to disease. Although tumor-associated biomarkers are promising liquid biopsy candidates, recent advances in biomarker enrichment and detection have allowed concentration on a new class of biomarker: tumor-derived biomarkers. This review focuses on making the distinction between the 2 biomarker categories and highlights promising new direction., (Copyright © 2022 Elsevier Inc. All rights reserved.)

While embryonic mammalian central nervous system (CNS) axons readily grow and differentiate, only a minority of fully differentiated mature CNS neurons are able to regenerate injured axons, leading to stunted functional recovery after injury and disease. To delineate DNA methylation changes specifically associated with axon regeneration, we used a Fluorescent-Activated Cell Sorting (FACS)-based methodology in a rat optic nerve transection model to segregate the injured retinal ganglion cells (RGCs) into regenerating and non-regenerating cell populations. Whole-genome DNA methylation profiling of these purified neurons revealed genes and pathways linked to mammalian RGC regeneration. Moreover, whole-methylome sequencing of purified uninjured adult and embryonic RGCs identified embryonic molecular profiles reactivated after injury in mature neurons, and others that correlate specifically with embryonic or adult axon growth, but not both. The results highlight the contribution to both embryonic growth and adult axon regeneration of subunits encoding the Na + /K + -ATPase. In turn, both biochemical and genetic inhibition of the Na + /K + -ATPase pump significantly reduced RGC axon regeneration. These data provide critical molecular insights into mammalian CNS axon regeneration, pinpoint the Na + /K + -ATPase as a key regulator of regeneration of injured mature CNS axons, and suggest that successful regeneration requires, in part, reactivation of embryonic signals., (© 2023. The Author(s).)

Human epidemiological studies reveal that dietary and environmental alterations influence the health of the offspring and that the effect is not limited to the F1 or F2 generations. Non-Mendelian transgenerational inheritance of traits in response to environmental stimuli has been confirmed in non-mammalian organisms including plants and worms and are shown to be epigenetically mediated. However, transgenerational inheritance beyond the F2 generation remains controversial in mammals. Our lab previously discovered that the treatment of rodents (rats and mice) with folic acid significantly enhances the regeneration of injured axons following spinal cord injury in vivo and in vitro , and the effect is mediated by DNA methylation. The potential heritability of DNA methylation prompted us to investigate the following question: Is the enhanced axonal regeneration phenotype inherited transgenerationally without exposure to folic acid supplementation in the intervening generations? In the present review, we condense our findings showing that a beneficial trait (i.e., enhanced axonal regeneration after spinal cord injury) and accompanying molecular alterations (i.e., DNA methylation), triggered by an environmental exposure (i.e., folic acid supplementation) to F0 animals only, are inherited transgenerationally and beyond the F3 generation., (© The Author(s) 2023. Published by Oxford University Press.)

The use of midline catheters has increased to reduce excessive use of central venous access devices, and additional data on midline catheter complications are needed. This study aimed to describe midline catheter complications among hospitalized patients. This retrospective study included a random sample of 300 hospitalized patients with a midline catheter insertion in 2019. The primary outcome was a composite end point of 8 complications: occlusion, bleeding at insertion site, infiltration/extravasation, catheter-related thrombosis, accidental removal, phlebitis, hematoma, and catheter-related infection. Midline catheter failure was defined as removal prior to the end of therapy due to complications. Among 300 midline catheters, the incidence of the composite end point of 1 or more midline complications was 38% (95% confidence interval, 33%-44%). Complications included occlusion (17.0%), bleeding at insertion site (12.0%), infiltration/extravasation (10.0%), catheter-related thrombosis (4.0%), accidental removal (3.0%), phlebitis (0.3%), hematoma (0.3%), and catheter-related infection (0.3%). Midline catheter failure occurred in 16% of midline catheters (n = 48) due to infiltration/extravasation (n = 27), accidental removal (n = 10), catheter-related thrombosis (n = 9), occlusion (n = 4), and catheter-related infection (n = 1). Three catheters had 2 types of failure. The most common complications of occlusion and bleeding rarely resulted in midline catheter failure. The most common causes of midline catheter failure were infiltration/extravasation, accidental removal, and catheter-related thrombosis., (Copyright © 2023 Infusion Nurses Society.)

Background: Solid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment., Methods: In this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients., Results: The study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04-2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46-0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72-2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53-1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36-1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64-2.08, P = 0.64)., Conclusions: Hospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Swan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Testing and vaccination have been major components of the strategy for combating the ongoing COVID-19 pandemic. In this study, we have developed a quantitative anti-SARS-CoV-2 spike (S1) IgG antibody assay using a fingerstick dried blood sample. We evaluated the feasibility of using this high-throughput and quantitative anti-SARS-CoV-2 spike (S1) IgG antibody testing assay in vaccinated individuals. Fingerstick blood samples were collected and analyzed from 137 volunteers before and after receiving the Moderna or Pfizer mRNA vaccine. Anti-SARS-CoV-2 S1 IgG antibody could not be detected within the first 7 days after receiving the first vaccine dose, however, the assay reliably detected antibodies from day 14 onwards. In addition, no anti-SARS-CoV-2 nucleocapsid (N) protein IgG antibody was detected in any of the vaccinated or healthy participants, indicating that the anti-SARS-CoV-2 S1 IgG assay is specific for the mRNA vaccine-induced antibodies. The S1 IgG levels detected in fingerstick samples correlated with the levels found in venous blood plasma samples and with the efficacy of venous blood plasma samples in the plaque reduction neutralization test (PRNT). The assay displayed a limit of quantification (LOQ) of 0.59 μg/mL and was found to be linear in the range of 0.51-1000 μg/mL. Finally, its clinical performance displayed a Positive Percent Agreement (PPA) of 100% (95% CI: 0.89-1.00) and a Negative Percent Agreement (NPA) of 100% (95% CI: 0.93-1.00). In summary, the assay described here represents a sensitive, precise, accurate, and simple method for the quantitative detection and monitoring of post-vaccination anti-SARS-CoV-2 spike IgG responses.

Background: Pharmacy residency programs provide research training experiences to residents, and publication is considered an indicator of high-quality research experiences., Objective: This study described attributes of pharmacy residents, residency programs, and residency major research projects and their associations with the outcome of publication in a peer-reviewed journal., Methods: Pharmacy residents who graduated from one academic medical center between 2001 and 2012 were invited to participate via an electronic survey distributed in February 2014. The survey collected attributes of the resident, residency program, and research project. The outcome of publication was self-reported by residents in 2014 and updated in July 2019 using a validated search strategy., Results: This study included 53 resident graduates representing 66 major pharmacy residency projects. Eighteen (27%) projects were published, occurring at an average of 13.8 months after residency graduation. The outcome of publication was more likely for residents with human subjects research experience prior to PGY1 training, residency programs that cultivated resident expertise in Institutional Review Board submission and statistical analysis, and projects with Institutional Review Board approval, a larger number of co-investigators, non-pharmacy co-investigators, and a larger sample size., Conclusion: This cohort of residents, programs, and projects at an academic medical center identified many modifiable attributes that were associated with successful publication of resident research projects. Unfortunately, residency projects rarely used study design features that attenuate bias. Residents and preceptors were perceived as having limited expertise with statistical analysis and database management, which underscores the need to develop research infrastructure to enhance research training for pharmacy students, residents, and preceptors.

Objective: This study described characteristics of wounds caused by animal exposures and evaluated patient factors and wound factors associated with wound infiltration of human rabies immune globulin (HRIG)., Materials and Methods: This retrospective cohort study evaluated wound characteristics among patients who had visible wounds and received HRIG or rabies vaccine for rabies postexposure prophylaxis (PEP) at 15 emergency departments from May 2016 to June 2018., Results: Of 110 included patients (9 children, 82 adults, and 19 older adults), 21% (n = 23) had ≥2 wounds, and 10% (n = 11) had infected wounds. Twenty-eight (25%) patients had severe wounds, defined as receiving sutures (n = 20) or reaching subcutaneous tissue or bone (n = 20). Wounds were present on upper extremities for 42% (n = 46) of patients, lower extremities for 35% (n = 38), head/face for 3% (n = 3), and in multiple locations for 21% (n = 23). Wounds were < 3 cm in length for 64% (n = 70) of patients. Puncture wounds were present in 60% (n = 66) of patients, abrasions in 45% (n = 49), and lacerations in 38% (n = 42). Among 108 wounds from 82 patients with documented HRIG administration sites, 57% (n = 62) of wounds received HRIG infiltration. Infiltration occurred less frequently for wounds on the face/head/torso (adjusted odds ratio [aOR] = 0.07, 95% confidence interval [CI] = 0.01 to 0.49), wounds on hands/fingers (aOR = 0.20, 95% CI = 0.06 to 0.65), and abrasion-only wounds (aOR = 0.26, 95% CI = 0.08 to 0.80) after adjusting for age., Conclusions: Upon presentation for rabies PEP, most patients did not have severe wounds and did not require emergency services or complex wound management. Wounds on the face, head, torso, hands, or fingers and abrasions were less likely to receive HRIG infiltration., Competing Interests: Declaration of Competing Interest JTS received an advisory board stipend that was paid to his employer by Kedrion Biopharma Inc. and investigator-initiated research funding that was paid to his employer by Grifols Shared Services North America, Inc. and Kedrion Biopharma Inc. (both are manufacturers of rabies immune globulin). TI, FY, ER, ATT, RBS, PRB, NAN, and DE report no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Gene therapeutic applications combined with bio- and nano-materials have been used to address current shortcomings in bone tissue engineering due to their feasibility, safety and potential capability for clinical translation. Delivery of non-viral vectors can be altered using gene-activated matrices to improve their efficacy to repair bone defects. Ex-situ and in-situ delivery strategies are the most used methods for bone therapy, which have never been directly compared for their potency to repair critical-sized bone defects. In this regard, we first time explore the delivery of polyethylenimine (PEI) complexed plasmid DNA encoding bone morphogenetic protein-2 (PEI-pBMP-2) using the two delivery strategies, ex-situ and in-situ delivery. To realize these gene delivery strategies, we employed intraoperative bioprinting (IOB), enabling us to 3D bioprint bone tissue constructs directly into defect sites in a surgical setting. Here, we demonstrated IOB of an osteogenic bioink loaded with PEI-pBMP-2 for the in-situ delivery approach, and PEI-pBMP-2 transfected rat bone marrow mesenchymal stem cells laden bioink for the ex-situ delivery approach as alternative delivery strategies. We found that in-situ delivery of PEI-pBMP-2 significantly improved bone tissue formation compared to ex-situ delivery. Despite debates amongst individual advantages and disadvantages of ex-situ and in-situ delivery strategies, our results ruled in favor of the in-situ delivery strategy, which could be desirable to use for future clinical applications., (© 2022 IOP Publishing Ltd.)

Background Idiopathic intracranial hypertension affects many women of childbearing age. However, the literature is sparse regarding pregnancy outcomes for these women. The goal of this study is to investigate the relationship between pregnancy outcomes in patients with a diagnosis of idiopathic intracranial hypertension. Methodology The TriNetX Research Network database was used to query 57 healthcare organizations for patients with idiopathic intracranial hypertension while pregnant (cohort 1) versus those who were pregnant without idiopathic intracranial hypertension (cohort 2). Cohorts were propensity-score matched for confounders related to pregnancy outcomes. The primary outcomes of interest were ectopic or molar pregnancy, cesarean section, abortion, preterm labor, depression, pre-eclampsia or eclampsia, and mortality. Chi-square analysis and logistic analysis were used on categorical variables. Results Ectopic/molar pregnancy was seen in 106 (1.75%) versus 117 (1.93%) (odds ratio (OR) 0.904, 95% confidence interval (CI) (0.694, 1.179), p = 0.4572) patients in cohorts 1 and 2, respectively. Cesarean section was seen in 785 (12.94%) versus 886 (14.59%) (OR 0.869, 95% CI (0.784, 0.964), p = 0.0078) patients, abortion in 536 (8.83%) versus 682 (11.24%) (OR 0.765, 95% CI (0.679, 0.862), p < 0.0001), preterm labor in 498 (8.206%) versus 668 (11.01%) (OR 0.723, 95% CI (0.640, 0.816), p < 0.0001), depression in 1,057 (17.42%) versus 1,061 (17.48%) (OR 0.995, 95% CI (0.906, 1.093), p = 0.9238), and pre-eclampsia/eclampsia in 501 (8.26%) versus 492 (8.11%) (OR 0.1.02, 95% CI (0.896, 1.161), p = 0.7657). Mortality was seen in 68 patients in cohort 1 versus 13 patients in cohort 2 (OR 5.279, 95% CI (2.913, 9.564), p < 0.0001). Conclusions This retrospective study examined pregnancy outcomes for pregnant women with a diagnosis of idiopathic intracranial hypertension. Women with idiopathic intracranial hypertension do not have an increase in rates of abortion, ectopic/molar pregnancy, cesarean section, preterm labor, or depression when compared to women without idiopathic intracranial hypertension. The mortality rate was higher in the idiopathic intracranial hypertension cohort, but still very low. This study demonstrates that pregnancy is generally well tolerated in the idiopathic intracranial hypertension population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hallan et al.)

Background Ion channels play a role in the development and progression of glioblastoma multiforme. This study investigates the association between the risk of developing glioblastoma multiforme in patients taking these medications. Methods A retrospective propensity score-matched analysis was performed using the TriNetX multinational electronic health record database for patients taking verapamil, digoxin, amiodarone, or diltiazem versus those not taking these medications. The outcome of interest was the incidence of glioblastoma multiforme. Results Verapamil users had an OR of 0.494 (p < 0.0001) of developing glioblastoma versus verapamil non-users. Patients on digoxin had an OR of 0.793 (p = 0.2393), patients on amiodarone had an OR of 0.600 (p = 0.0035), patients on diltiazem had an OR of 0.584 (p < 0.0001), and patients on verapamil, digoxin, amiodarone, or diltiazem had an OR of 0.641 (p < 0.0001) of developing glioblastoma versus patients not taking these medications. Conclusion In patients taking the ion channel blockers diltiazem, amiodarone, or verapamil, the odds of developing glioblastoma multiforme were lower than in patients not taking these medications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hallan et al.)

The posterior femoral cutaneous nerve (PFCN) is an extensive nerve with numerous collateral branches which provide cutaneous innervation to 2/3 rds of the posterior thigh, the infragluteal fold, as well as the lateral anal region, scrotum, and labia majora through its inferior cluneal and pudendal nerve branches. It has been noted in multiple studies that patients can experience persistent PFCN neuropathy after surgery for decompression of known collateral branches. In this study, we used 17 formaldehyde (7 male and 10 female) perfused cadavers obtained from Hershey Medical Center's donor program to study the branching patterns of the PFCN. As a result, we found that 41% of individuals have an unidentified proximal branch of PFCN that recurs over the inferolateral border of the gluteus maximus, suggesting other areas of potential compression or nerve entrapment that could lead to persistent PFCN neuropathy that's not improved after treatment for sciatic, pudendal, or inferior cluneal neuralgia. We hope these findings allow clinicians to modify current surgical techniques and improve patients' post-operative quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jennette et al.)

Background Ten percent of women of childbearing age have histologically confirmed meningioma. To date, little is known regarding pregnancy-related outcomes for women with meningioma. Methods We used a de-identified database network (TriNetX's Research Network, https://trinetx.com/) to gather information on pregnant patients with meningioma (cohort 1) versus pregnant patients without meningioma (cohort 2). The primary outcome of interest included the impact of meningioma on mortality at one year. Secondary endpoints included ectopic or molar pregnancy, cesarean section, abortion, preterm labor, depression, pre-eclampsia/eclampsia, and craniotomy. Odds ratios (OR) with 95% confidence intervals (CI) were used to measure levels of association between each cohort and the outcomes of interest. Results A total of 1,739 patients were identified in each cohort following propensity-score matching. Mortality was seen in 23 patients (1.32%) in cohort 1 versus 26 patients (1.41%) in cohort 2 (OR 0.88, 95% CI {0.50, 1.55}, p=0.66). Ectopic/ molar pregnancy was seen in 31 (1.78%) versus 42 (2.42%) patients in cohorts 1 and 2, respectively (OR 0.73, 95% CI {0.046,1.17}, p=0.19). Cesarean section was seen in 126 (7.25%) versus 164 (9.43%) patients, respectively (OR 0.75, 95% CI {0.59,0.97}, p=0.020). Abortion was seen in 128 (7.36%) versus 183 (10.52%) patients, respectively (OR 0.68, 95% CI {0.53,0.86}, p=0.0011). Preterm labor was seen in 75 (4.31%) versus 119 (6.84%) patients, respectively (OR 0.61, 95% CI {0.46,0.83}, p=0.0012). Depression was seen in 258 (14.84%) versus 270 (15.53%) patients, respectively (OR 0.95, 95% CI {0.79,1.14}, p=0.57). Pre-eclampsia/eclampsia was seen in 3.11% versus 5.52% patients, respectively (OR 0.55, 95% CI {0.39,0.77}, p=0.0005). Craniotomy was seen in 74 (4.26%) versus 0 (0%) patients in cohort 1 and cohort 2, respectively. Conclusion Patients with meningioma were not at higher risk for pregnancy complications, including ectopic/molar pregnancy, cesarean section, abortion, preterm labor, pre-eclampsia/eclampsia, and mortality, compared to their non-meningioma counterparts. Still, coordinated care by neurosurgical and obstetrical providers may benefit women with meningiomas who are planning for pregnancy or are currently pregnant., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hallan et al.)

Background: Despite the increasing popularity of midline catheters, data on the use of alteplase for restoring midline catheter patency is scarce., Aims: This study aimed to evaluate off-label use of alteplase for midline catheter occlusions., Method: Adults who received alteplase into a midline catheter between January 2015 and May 2018 within a multi-hospital health system were included in this study. The primary outcome was restoration of infusion or withdrawal function from at least one lumen of a treated midline catheter., Findings: Following alteplase administration, withdrawal function was restored in 47% (25/53) of occlusion events, infusion function was restored in 65% (11/17) of complete occlusion events, and infusion or withdrawal function was restored in 58% (31/53) of occlusion events. Only 34% (17/50) of catheters were replaced because of malfunction. Local bleeding was documented in 9% ( n =5) of occlusion events after alteplase administration., Conclusion: Most midline catheter occlusions treated with alteplase demonstrated restoration of infusion or withdrawal function.

Introduction: COVID-19 patients frequently experience headaches, malaise, and fatigue. For patients with shunted hydrocephalus, these signs and symptoms can often be indicative of shunt failure. Thus, it can be challenging to determine if shunt failure has occurred in this patient population. Therefore, we explored the question of how a diagnosis of COVID-19 in shunted hydrocephalus patients influences the rate of shunt revision., Methods: We used a deidentified database network (TriNetX) to gather information on patients with shunted hydrocephalus and COVID-19 versus no COVID-19 from January 20, 2020, through September 26, 2021. Our primary outcome of interest was shunt revision at 90 days, with secondary outcomes of mortality, hospitalization, ICU admission, mechanical ventilation, tracheostomy, PEG tube placement, fall, seizure, acute kidney injury (AKI), venous thromboembolism (VTE), ischemic stroke (I.S.), myocardial infarction (MI), and sepsis. Cohorts were propensity score-matched for common comorbidities and demographics., Results: After propensity score matching, 10,600 patients with shunted hydrocephalus and COVID-19 (cohort 1) and 10,600 patients with shunted hydrocephalus and no COVID-19 (cohort 2) were identified. Average age was 38.5 years. Eight hundred and thirty-four patients (7.869%) in cohort 1 and 180 (1.698%) patients in cohort 2 underwent shunt revision (p=<0.0001, OR 4.978, 95% CI 4.198, 5.821). Mortality was 4.642% vs. 2.113% (p<0.0001, OR 2.255, 95% CI 1.921, 2.647). Hospitalization rates were 27.72% vs. 10.303% (p<0.0001), and ICU admission rates 11.567% vs. 3.463% (p<0.0001). Ventilator dependence was 3.529% vs. 0.953% (p<0.0001), tracheostomy 1.142% vs. 0.236% (p<0.0001), PEG tube insertion 2.472% vs. 0.585% (p<0.0001), falls 2.321% vs. 1.076% (p<0.0001), seizure 11.369% vs. 5.953% (p<0.0001), AKI 4.416% vs. 1.717% (p<0.0001), VTE 3.538% vs. 1.293% (p<0.0001), sepsis 3.887% vs. 1.179% (p<0.0001), IS 0.585% vs. 0.16% (p<0.0001), and MI 1.34% vs. 0.519% (p<0.0001)., Conclusion: COVID-19 infection is associated with an almost five-fold increase in shunt revisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hallan et al.)

Purpose: Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region of the cerebral hemispheres or the ciliary body of the eye. Even rarer still is the extracranial manifestation of medulloepithelioma with only 12 cases reported to date. Our purpose is to report a case of an intradural, extra-medullary medulloepithelioma and review the limited literature about diagnosis and treatment of this extremely rare pathology., Methods: PubMed was queried using search terms "peripheral medulloepithelioma" and "pre-sacral medulloepithelioma." Medulloepitheliomas which were intraocular or occurred in reproductive organs were excluded. Patients' age, sex, the symptomatic period prior to diagnosis, primary tumor site, stage, treatment regimen, pathologic description, and survival outcomes were collected., Results: We present a case of extracranial medulloepithelioma in an 8-year-old male. Morphology of the neoplasm was representative of medulloepithelioma but there was no amplification of C19MC. Additionally, the neoplasm stained positive for CD99. Twelve other cases of extracranial medulloepithelioma were found in literature review., Conclusions: The rarity of extracranial medulloepithelioma makes for a challenging diagnosis. Designing an optimal treatment strategy is difficult because of a scarcity of cases and wide variety in locations and treatments. Our case provides an example of treatment including resection, intense induction chemotherapy, consolidation with high-dose chemotherapy and stem cell rescue, craniospinal proton radiation therapy, and metronomic chemotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)