Interpretation of Data from Translational Rodent Nerve Injury and Repair Models.

This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.

Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.

Neurofibromatosis type 1, a genetic disorder caused by germline mutations in NF1, predisposes patients to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas, and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors such as glioblastoma (GBM), melanoma, breast, ovarian, and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy, and lysosome positioning in NF1-deficient cells. A dual proteomics approach identified the BORC complex, which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown of a BORC complex subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that the BORC complex may be a promising therapeutic target for NF1-deficient tumors.

Instrumented Mouthguard Decoupling Affects Measured Head Kinematic Accuracy.

Many recent studies have used boil-and-bite style instrumented mouthguards to measure head kinematics during impact in sports. Instrumented mouthguards promise greater accuracy than their predecessors because of their superior ability to couple directly to the skull. These mouthguards have been validated in the lab and on the field, but little is known about the effects of decoupling during impact. Decoupling can occur for various reasons, such as poor initial fit, wear-and-tear, or excessive impact forces. To understand how decoupling influences measured kinematic error, we fit a boil-and-bite instrumented mouthguard to a 3D-printed dentition mounted to a National Operating Committee on Standards for Athletic Equipment (NOCSAE) headform. We also instrumented the headform with linear accelerometers and angular rate sensors at its center of gravity (CG). We performed a series of pendulum impact tests, varying impactor face and impact direction. We measured linear acceleration and angular velocity, and we calculated angular acceleration from the mouthguard and the headform CG. We created decoupling conditions by varying the gap between the lower jaw and the bottom face of the mouthguard. We tested three gap conditions: 0 mm (control), 1.6 mm, and 4.8 mm. Mouthguard measurements were transformed to the CG and compared to the reference measurements. We found that gap condition, impact duration, and impact direction significantly influenced mouthguard measurement error. Error was higher for larger gaps and in frontal (front and front boss) conditions. Higher errors were also found in padded conditions, but the mouthguards did not collect all rigid impacts due to inherent limitations. We present characteristic decoupling time history curves for each kinematic measurement. Exemplary frequency spectra indicating characteristic decoupling frequencies are also described. Researchers using boil-and-bite instrumented mouthguards should be aware of their limitations when interpreting results and should seek to address decoupling through advanced post-processing techniques when possible.

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

An overview of the current diagnostic approach to Periprosthetic Joint Infections.

The diagnosis of periprosthetic joint infections (PJI) presents a formidable challenge to orthopaedic surgeons due to its complex and diverse manifestations. Accurate diagnosis is of utmost importance, as even mild pain following joint replacement surgery may indicate PJI in the absence of a definitive gold standard diagnostic test. Numerous diagnostic modalities have been suggested in the literature, and international societies have continually updated diagnostic criteria for this debilitating complication. This review article aims to comprehensively examine the latest evidence-based approaches for diagnosing PJI. Through a thorough analysis of current literature, we explore promising diagnostic strategies that have demonstrated effectiveness in identifying PJI. These strategies encompass the utilization of laboratory markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), alongside imaging techniques such as magnetic resonance imaging (MRI) and leukocyte scintigraphy. Additionally, we highlight the importance of synovial fluid analysis, including the potential role of alpha-defensin as a biomarker, and examine evolving international diagnostic criteria to standardize and improve diagnostic accuracy.

Scalable purification of extracellular vesicles with high yield and purity using multimodal flowthrough chromatography.

Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell-cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co-isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins. In the pursuit of improved EV isolation techniques, we introduce multimodal flowthrough chromatography (MFC) as a scalable alternative to size exclusion chromatography (SEC). The use of MFC offers significant advantages for purifying EVs, resulting in enhanced yields and increased purity with respect to protein and nucleic acid co-isolates from conditioned 3D cell culture media. Compared to SEC, significantly higher EV yields with similar purity and preserved functionality were also obtained with MFC in 2D cell cultures. Additionally, MFC yielded EVs from serum with comparable purity to SEC and similar apolipoprotein B content. Overall, MFC presents an advancement in EV purification yielding EVs with high recovery, purity, and functionality, and offers an accessible improvement to researchers currently employing SEC.

A RAD18-UBC13-PALB2-RNF168 axis mediates replication fork recovery in BRCA1-deficient cancer cells.

BRCA1/2 proteins function in genome stability by promoting repair of double-stranded DNA breaks through homologous recombination and by protecting stalled replication forks from nucleolytic degradation. In BRCA1/2-deficient cancer cells, extensively degraded replication forks can be rescued through distinct fork recovery mechanisms that also promote cell survival. Here, we identified a novel pathway mediated by the E3 ubiquitin ligase RAD18, the E2-conjugating enzyme UBC13, the recombination factor PALB2, the E3 ubiquitin ligase RNF168 and PCNA ubiquitination that promotes fork recovery in BRCA1- but not BRCA2-deficient cells. We show that this pathway does not promote fork recovery by preventing replication fork reversal and degradation in BRCA1-deficient cells. We propose a mechanism whereby the RAD18-UBC13-PALB2-RNF168 axis facilitates resumption of DNA synthesis by promoting re-annealing of the complementary single-stranded template strands of the extensively degraded forks, thereby allowing re-establishment of a functional replication fork. We also provide preliminary evidence for the potential clinical relevance of this novel fork recovery pathway in BRCA1-mutated cancers, as RAD18 is over-expressed in BRCA1-deficient cancers, and RAD18 loss compromises cell viability in BRCA1-deficient cancer cells.

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

Isolated Osseous Excision in the Adult Carpus: A Narrative Review.

Various pathologies of the adult carpus result in clinical scenarios where excision can be considered and even recommended. In the appropriate patient population, isolated carpal excision can alleviate pain and improve mobility. Excisions of the pisiform, trapezium, and trapezoid have abundant literature evidence to support positive long-term functional outcomes. In contrast, isolated excision of the capitate, hamate, and triquetrum has limited support in the literature secondary to compromise of carpal mechanics and lead to recurrent pain. Additionally, isolated scaphoid and lunate excision are best avoided secondary to carpal collapse and should be paired with concomitant stabilizing procedures in the carpus. This article provides a comprehensive literature review of isolated excision of each osseous carpal bone, their indications, and previously assessed outcomes.

Periprosthetic tibial fracture as a complication of unicompartmental knee arthroplasty: Current insights.

Periprosthetic fracture following knee arthroplasty is a rare but devastating complication associated with significant morbidity. With unicompartmental knee arthroplasty being performed far less frequently than total knee arthroplasty, periprosthetic fracture following unicompartmental knee arthroplasty presents a particular challenge to orthopaedic surgeons, due to clinical unfamiliarity and sparsity of literature. An up-to-date review of the epidemiology, risk factors, and management strategies for PPF after UKA is presented.

Periprosthetic Distal Femoral Fractures Around a Total Knee Arthroplasty: a Meta-analysis Comparing Locking compression Plating and Retrograde Intramedullary Nailing.

Purpose: The number of total knee replacements (TKRs) performed per year has been increasing annually and it is estimated that by 2030 demand would reach 3.48 million procedures per year in the United States Of America. The prevalence of periprosthetic fractures (PPFs) around TKRs has followed this trend with incidences ranging from 0.3% to 3.5%. Distal femoral PPFs are associated with significant morbidity and mortality. When there is sufficient bone stock in the distal femur and a fracture pattern conducive to fixation, locking compression plating (LCP) and retrograde intramedullary nailing (RIMN) are commonly used fixation strategies. Conversely, in situations with loosening and deficient bone stock, a salvage procedure such as a distal femoral replacement is recognized as an alternative. This meta-analysis investigates the rates of non-union, re-operation, infection, and mortality for LCPs and RIMNs when performed for distal femoral PPFs fractures around TKRs. Method: A search was conducted to identify articles relevant to the management of distal femoral PPFs around TKRs in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Articles meeting the inclusion criteria were then assessed for methodological quality using the methodological items for non-randomised studies (MINORS) criteria. Articles were reviewed, and data were compiled into tables for analysis. Results: 10 articles met the inclusion criteria, reporting on 528 PPFs. The overall incidence of complications was: non-union 9.4%, re-operation 12.9%, infection 2.4%, and mortality 5.5%. This meta-analysis found no significant differences between RIMN and LCP in rates of non-union (9.2% vs 9.6%) re-operation (15.1% vs 11.3%), infection (2.1% vs 2.6%), and mortality (6.0% vs 5.2%), respectively. Conclusion: This meta-analysis demonstrated no significant difference in rates of non-union, re-operation, infection, and mortality between RIMN and LCP and both remain valid surgical treatment options.

Reduced Capsaicin-Induced Mechanical Allodynia and Neuronal Responses in the DRG in the Presence of Ptpn6 Overexpression.

Transient Receptor Potential Vanilloid 1 (TRPV1) is a nonselective cation channel expressed by pain-sensing neurons and has been an attractive target for the development of drugs to treat pain. Recently, Src homology region 2 domain-containing phosphatase-1 (SHP-1, encoded by Ptpn6) was shown to dephosphorylate TRPV1 in dorsal root ganglia (DRG) neurons, which was linked with alleviating different pain phenotypes. These previous studies were performed in male rodents only and did not directly investigate the role of SHP-1 in TRPV-1 mediated sensitization. Therefore, our goal was to determine the impact of Ptpn6 overexpression on TRPV1-mediated neuronal responses and capsaicin-induced pain behavior in mice of both sexes. Twelve-week-old male and female mice overexpressing Ptpn6 (Shp1-Tg) and their wild type (WT) littermates were used. Ptpn6 overexpression was confirmed in the DRG of Shp1-Tg mice by RNA in situ hybridization and RT-qPCR. Trpv1 and Ptpn6 were found to be co-expressed in DRG sensory neurons in both genotypes. Functionally, this overexpression resulted in lower magnitude intracellular calcium responses to 200 nM capsaicin stimulation in DRG cultures from Shp1-Tg mice compared to WTs. In vivo, we tested the effects of Ptpn6 overexpression on capsaicin-induced pain through a model of capsaicin footpad injection. While capsaicin injection evoked nocifensive behavior (paw licking) and paw swelling in both genotypes and sexes, only WT mice developed mechanical allodynia after capsaicin injection. We observed similar level of TRPV1 protein expression in the DRG of both genotypes, however, a higher amount of tyrosine phosphorylated TRPV1 was detected in WT DRG. These experiments suggest that, while SHP-1 does not mediate the acute swelling and nocifensive behavior induced by capsaicin, it does mediate a protective effect against capsaicin-induced mechanical allodynia in both sexes. The protective effect of SHP-1 might be mediated by TRPV1 dephosphorylation in capsaicin-sensitive sensory neurons of the DRG.

Distal femoral replacement for the treatment of periprosthetic distal femoral fractures around a total knee arthroplasty: a meta-analysis.

Background: Periprosthetic fracture is a rare complication of arthroplasty but can have devastating consequences for the patient and presents a complex surgical challenge. Locking compression plate and retrograde intramedullary nail are both widely accepted surgical fixation techniques for distal femoral periprosthetic fractures around a total knee arthroplasty. Although there is still a need for further high-quality research into both techniques, there is even less literature concerning the use of distal femoral replacement to treat distal femoral periprosthetic fractures. Interest has been piqued in distal femoral replacements for the treatment of distal femoral periprosthetic fractures due to the theoretical advantages of immediate post-operative weight-bearing and lack of dependence on fracture union, but there are still understandably reservations about performing such an extensive and invasive procedure when an accepted alternative is available. This meta-analysis aims to evaluate the current literature to compare the complication rates and return to pre-operative ambulatory status of distal femoral replacement and locking compression plate. Method: A literature search was performed to identify articles related to the management of distal femoral periprosthetic fractures around a total knee arthroplasty in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Methodological quality was assessed using the methodological index for non-randomized studies (MINORS) criteria. Articles were reviewed, and data extracted for analysis. Results: Five articles met the inclusion criteria, reporting on 345 periprosthetic fractures. The overall rates of complications for distal femoral replacement and locking compression plate were: re-operation (6.1% vs 12.1%), infection (3.0% vs 5.3%), mortality (19.7% vs 19.3%), and return to pre-operative ambulatory status (60.9% vs 71.8%) (respectively). Conclusion: This meta-analysis shows no statistically significant difference in the rates of re-operation, infection, mortality or return to pre-operative ambulatory status when comparing distal femoral replacement to locking compression plate.

Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma.

BACKGROUND: Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. METHODS: We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children's Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated. RESULTS: Thirty-three patients (18 male; median age, 5 years) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (n = 10, 30%). Most tumors were in the cerebral hemispheres (n = 22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3% ±â€…8.3%; the 5-year overall survival (OS) rate was 96.4% ±â€…4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6% ±â€…15.2% (P < .01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways. CONCLUSIONS: pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.

Modeling protective action decision-making in earthquakes by using explainable machine learning and video data.

Earthquakes pose substantial threats to communities worldwide. Understanding how people respond to the fast-changing environment during earthquakes is crucial for reducing risks and saving lives. This study aims to study people's protective action decision-making in earthquakes by leveraging explainable machine learning and video data. Specifically, this study first collected real-world CCTV footage and video postings from social media platforms, and then identified and annotated changes in the environment and people's behavioral responses during the M7.1 2018 Anchorage earthquake. By using the fully annotated video data, we applied XGBoost, a widely-used machine learning method, to model and forecast people's protective actions (e.g., drop and cover, hold on, and evacuate) during the earthquake. Then, explainable machine learning techniques were used to reveal the complex, nonlinear relationships between different factors and people's choices of protective actions. Modeling results confirm that social and environmental cues played critical roles in affecting the probability of different protective actions. Certain factors, such as the earthquake shaking intensity and number of people shown in the environment, displayed evident nonlinear relationships with the probability of choosing to evacuate. These findings can help emergency managers and policymakers design more effective protective action recommendations during earthquakes.

Crystal structure and analytical profile of 1,2-diphenyl-2-pyrrolidin-1-ylethanone hydrochloride or `α-D2PV': a synthetic cathinone seized by law enforcement, along with its diluent sugar, myo-inositol.

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT-IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant complete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hydrochloride hemihydrate or 1-(2-oxo-1,2-diphenylethyl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+·Cl-·0.5H2O, (I), a synthetic cathinone called `α-D2PV', and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) interesting hydrogen bonding observed in pairwise interactions by the drug molecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π-π interactions in the case of the phenyl rings of the drug which are of two different types, namely, π-π stacking and edge-to-π. Finally, the inositol crystallizes with Z' = 2 and the resulting diastereoisomers were examined by overlay techniques.

Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

Why is early-onset atrial fibrillation uncommon in patients with Duchenne muscular dystrophy? Insights from the mdx mouse.

AIMS: A reduction in both dystrophin and neuronal nitric oxide synthase (NOS1) secondary to microRNA-31 (miR-31) up-regulation contributes to the atrial electrical remodelling that underpins human and experimental atrial fibrillation (AF). In contrast, patients with Duchenne muscular dystrophy (DMD), who lack dystrophin and NOS1 and, at least in the skeletal muscle, have raised miR-31 expression, do not have increase susceptibility to AF in the absence of left ventricular (LV) dysfunction. Here, we investigated whether dystrophin deficiency is also associated with atrial up-regulation of miR-31, loss of NOS1 protein, and increased AF susceptibility in young mdx mice. METHODS AND RESULTS: Echocardiography showed normal cardiac structure and function in 12-13 weeks mdx mice, with no indication by assay of hydroxyproline that atrial fibrosis had developed. The absence of dystrophin in mdx mice was accompanied by an overall reduction in syntrophin and a lower NOS1 protein content in the skeletal muscle and in the left atrial and ventricular myocardium, with the latter occurring alongside reduced Nos1 transcript levels (exons 1-2 by quantitative polymerase chain reaction) and an increase in NOS1 polyubiquitination [assessed using tandem polyubiquitination pulldowns; P < 0.05 vs. wild type (WT)]. Neither the up-regulation of miR-31 nor the substantial reduction in NOS activity observed in the skeletal muscle was present in the atrial tissue of mdx mice. At difference with the skeletal muscle, the mdx atrial myocardium showed a reduction in the constitutive NOS inhibitor, caveolin-1, coupled with an increase in NOS3 serine1177 phosphorylation, in the absence of differences in the protein content of other NOS isoforms or in the relative expression NOS1 splice variants. In line with these findings, transoesophageal atrial burst pacing revealed no difference in AF susceptibility between mdx mice and their WT littermates. CONCLUSION: Dystrophin depletion is not associated with atrial miR-31 up-regulation, reduced NOS activity, or increased AF susceptibility in the mdx mouse. Compared with the skeletal muscle, the milder atrial biochemical phenotype may explain why patients with DMD do not exhibit a higher prevalence of atrial arrhythmias despite a reduction in NOS1 content.

Obesity and meningioma: a US population-based study paired with analysis of a multi-institutional cohort.

OBJECTIVE: Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort. METHODS: National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS. RESULTS: From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043). CONCLUSIONS: Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

Using Clinical Decision Support Systems to Decrease Intravenous Acetaminophen Use: Implementation and Lessons Learned.

BACKGROUND: Clinical decision support systems (CDSS) can enhance medical decision-making by providing targeted information to providers. While they have the potential to improve quality of care and reduce costs, they are not universally effective and can lead to unintended harm. OBJECTIVES: To describe the implementation of an unsuccessful interruptive CDSS that aimed to promote appropriate use of intravenous (IV) acetaminophen at an academic pediatric hospital, with an emphasis on lessons learned. METHODS: Quality improvement methodology was used to study the effect of an interruptive CDSS, which set a mandatory expiry time of 24 hours for all IV acetaminophen orders. This CDSS was implemented on April 5, 2021. The primary outcome measure was number of IV acetaminophen administrations per 1,000 patient days, measured pre- and postimplementation. Process measures were the number of IV acetaminophen orders placed per 1,000 patient days. Balancing measures were collected via survey data and included provider and nursing acceptability and unintended consequences of the CDSS. RESULTS: There was no special cause variation in hospital-wide IV acetaminophen administrations and orders after CDSS implementation, nor when the CDSS was removed. A total of 88 participants completed the survey. Nearly half (40/88) of respondents reported negative issues with the CDSS, with the majority stating that this affected patient care (39/40). Respondents cited delays in patient care and reduced efficiency as the most common negative effects. CONCLUSION: This study underscores the significance of monitoring CDSS implementations and including end user acceptability as an outcome measure. Teams should be prepared to modify or remove CDSS that do not achieve their intended goal or are associated with low end user acceptability. CDSS holds promise for improving clinical practice, but careful implementation and ongoing evaluation are crucial for maximizing their benefits and minimizing potential harm.