High Accuracy of Intra-articular Needle Position during Anterior Landmark Guided Glenohumeral Injections.

OBJECTIVES: Image-guided ultrasound or fluoroscopic glenohumeral injections have high accuracy rates, but require training, equipment, cost, and radiation exposure (fluoroscopy). In contrast, landmark-guided glenohumeral injections do not require additional subspecialist referral or equipment. An optimal technique would be safe, accurate, and have few barriers to implementation. The purpose of this study was to define the accuracy of glenohumeral needle placement via an anterior landmark-guided approach as assessed by direct arthroscopic visualization. METHODS: A consecutive series of adult patients undergoing shoulder arthroscopy in the beach chair position were included in this study. Demographic and procedural data were collected. Time required to perform the injection, precise location of the needle-tip, and factors that affected accuracy of injection were also assessed. RESULTS: A standardized anterior landmark-guided glenohumeral joint injection was performed in the operating room prior to surgery and location of the needle tip was documented by arthroscopic visualization with a low complication profile and few barriers to implementation. A total of 81 patients were enrolled. Successful intra-articular glenohumeral needle placement by Sports Medicine and Shoulder/elbow fellowship trained orthopaedic surgeons was confirmed in 93.8% (76/81) of patients. Average time to complete the procedure was 24.8 seconds. There were no patient-related variables associated with non-intra-articular injection in the cohort. CONCLUSIONS: This study demonstrated a technique of anterior landmark-guided glenohumeral injection has an accuracy of 93.8% and requires less than 30 seconds to perform. This method is safe, yields similar accuracy to image-guided procedures with improved cost-and time-efficiency, and less radiation exposure. No patient-related factors were associated with inaccurate needle placement. Anterior landmark-guided glenohumeral injections may be utilized with confidence by providers in the clinical setting. LEVEL OF EVIDENCE: Level 5.

The effectiveness of targeted muscle reinnervation in reducing pain and improving quality of life for patients following lower limb amputation.

BACKGROUND: Globally, over 1 million lower limb amputations are performed annually, with approximately 75% of patients experiencing significant pain, profoundly impacting their quality of life and functional capabilities. Targeted muscle reinnervation (TMR) has emerged as a surgical solution involving the rerouting of amputated nerves to specific muscle targets. Originally introduced to enhance signal amplification for myoelectric prosthesis control, TMR has expanded its applications to include neuroma management and pain relief. However, the literature assessing patient outcomes is lacking, specifically for lower limb amputees. This systematic review aims to assess the effectiveness of TMR in reducing pain and enhancing functional outcomes for patients who have undergone lower limb amputation. METHODS: A systematic review was performed by examining relevant studies between 2010 and 2023, focusing on pain reduction, functional outcomes and patient-reported quality of life measures. RESULTS: In total, 20 studies were eligible encompassing a total of 778 extremities, of which 75.06% (n = 584) were lower limb amputees. Average age was 46.66 years and patients were predominantly male (n = 70.67%). Seven studies (35%) reported functional outcomes. Patients who underwent primary TMR exhibited lower average patient-reported outcome measurement information system (PROMIS) scores for phantom limb pain (PLP) and residual limb pain (RLP). Secondary TMR led to improvements in PLP, RLP and general limb pain as indicated by average numeric rating scale and PROMIS scores. CONCLUSION: The systematic review underscores TMR's potential benefits in alleviating pain, fostering post-amputation rehabilitation and enhancing overall well-being for lower limb amputees.

Suture Anchor Technique for Bridge Enhanced Anterior Cruciate Ligament Restoration.

Anterior cruciate ligament (ACL) injuries are common in the athletic population. ACL repair with bridge enhancement is an emerging technology with promising clinical outcomes in patients with a proximal to midsubstance ACL tears. Currently, there are a variety of fixation methods described for isolated ACL repair, including suspensory and anchor techniques. This Technical Note describes a bridge enhanced ACL restoration procedure technique, using suture anchors for the femoral fixation. Advantages of this technique include more rigid fixation and avoiding need for accessory over-the-top incision. Additionally, the surgical workflow is more similar to an ACL reconstruction with intra-articular screw fixation, which may be more readily adopted by some surgeons.

Symptomatic brain metastases in melanoma.

Although clinical outcomes in metastatic melanoma have improved in recent years, the morbidity and mortality of symptomatic brain metastases remain challenging. Response rates and survival outcomes of patients with symptomatic melanoma brain metastases (MBM) are significantly inferior to patients with asymptomatic disease. This review focusses upon the specific challenges associated with the management of symptomatic MBM, discussing current treatment paradigms, obstacles to improving clinical outcomes and directions for future research.

Characterization of gastric dysfunction after fundoplication using body surface gastric mapping.

BACKGROUND: Adverse gastric symptoms persist in up to 20% of fundoplication operations completed for gastroesophageal reflux disease, causing significant morbidity and driving the need for revisional procedures. Noninvasive techniques to assess the mechanisms of persistent postoperative symptoms are lacking. This study aimed to investigate gastric myoelectrical abnormalities and symptoms in patients after fundoplication using a novel noninvasive body surface gastric mapping (BSGM) device. METHODS: Patients with a previous fundoplication operation and ongoing significant gastroduodenal symptoms and matched controls were included. BSGM using Gastric Alimetry (Alimetry Ltd) was employed, consisting of a high-resolution 64-channel array, validated symptom-logging application, and wearable reader. RESULTS: A total of 16 patients with significant chronic symptoms after fundoplication were recruited, with 16 matched controls. Overall, 6 of 16 patients (37.5%) showed significant spectral abnormalities defined by unstable gastric myoelectrical activity (n = 2), abnormally high gastric frequencies (n = 3), or high gastric amplitudes (n = 1). Patients with spectral abnormalities had higher Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index scores than those of patients without spectral abnormalities (3.2 [range, 2.8-3.6] vs 2.3 [range, 2.2-2.8], respectively; P = .024). Moreover, 7 of 16 patients (43.8%) had BSGM test results suggestive of gut-brain axis contributions and without myoelectrical dysfunction. Increasing Principal Gastric Frequency Deviation and decreasing Rhythm Index scores were associated with symptom severity (r > .40; P < .05). CONCLUSION: A significant number of patients with persistent postfundoplication symptoms displayed abnormal gastric function on BSGM testing, which correlated with symptom severity. Our findings advance the pathophysiologic understanding of postfundoplication disorders, which may inform diagnosis and patient selection for medical therapy and revisional procedures.

Is Insurance Payer Associated With Hospital Admission of Emergency Department Patients With Mandible Fractures?

BACKGROUND: There is a lack of consensus on the optimal triage pathway for emergency department (ED) patients with mandibular fractures. It remains unclear if patient insurance payers predict hospital admission given potentially competing logistical and health system incentives. PURPOSE: To generate nationally representative estimates of the frequency of hospital admission and its association with primary insurance payers for ED patients with mandible fractures. METHODS: This retrospective cohort study used the 2018 Nationwide Emergency Department Sample, the largest all-payer database in the United States, to identify patients with mandible fractures. The database includes a stratified sample with discharge weights to generate nationally representative estimates. Patients with other facial fractures and/or concomitant injuries that independently warranted admission were excluded. PREDICTOR: The primary predictor variable was primary payer (public, private, self-pay, and other/no charge). OUTCOME VARIABLE: The primary outcome variable was hospital admission (yes/no). COVARIATES: Covariates included patient-, medical/injury-, and hospital-related variables. ANALYSES: Descriptive statistics, along with bivariate and multivariate logistic regression with Bonferroni correction, were used to produce national estimates and identify predictors of admission. P < .01 was considered significant. RESULTS: The cohort included 27,238 weighted encounters involving isolated mandible fractures, of which 5,345(20%) were admitted. The payers for admitted patients were 46% public, 25% private, 22% self-pay, and 7% no charge/other. In bivariate analyses, public insurance was associated with a higher likelihood of admission than private insurance (RR 1.24, 95% CI 1.06 to 1.45), though there was no association in the multivariate model (OR 1.03, 95% CI 0.83 to 1.28). In multivariate analysis, higher Charlson Comorbidity Index (OR 1.32, 95% CI 1.18 to 1.48), alcohol-related disorder (OR 3.47, 95% CI 2.74 to 4.39), substance-related disorder (OR 1.43, 95% CI 1.20 to 1.71), and more mandible fractures (OR 3.08, 95% CI 2.65 to 3.59) were associated with admission. Compared to body fractures, subcondylar (OR 3.83, 95% CI 2.39 to 6.14), angle (OR 3.53, 95% CI 2.84 to 6.09), and symphysis (OR 4.14, 95% CI 2.84 to 6.09) fractures had higher odds of admission. Finally, level I (OR 4.11, 95% CI 2.41 to 6.98) and level II (OR 3.16, 95% CI 1.85 to 5.39) trauma centers had higher odds of admission. CONCLUSIONS: In 2018, 20% of ED patients with isolated mandible fractures were admitted. Several patient and hospital characteristics were predictors of admission. Insurance status was not associated with admission.

Brain-wide neural activity underlying memory-guided movement.

Behavior relies on activity in structured neural circuits that are distributed across the brain, but most experiments probe neurons in a single area at a time. Using multiple Neuropixels probes, we recorded from multi-regional loops connected to the anterior lateral motor cortex (ALM), a circuit node mediating memory-guided directional licking. Neurons encoding sensory stimuli, choices, and actions were distributed across the brain. However, choice coding was concentrated in the ALM and subcortical areas receiving input from the ALM in an ALM-dependent manner. Diverse orofacial movements were encoded in the hindbrain; midbrain; and, to a lesser extent, forebrain. Choice signals were first detected in the ALM and the midbrain, followed by the thalamus and other brain areas. At movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

The Discovery of Exarafenib (KIN-2787): Overcoming the Challenges of Pan-RAF Kinase Inhibition.

RAF, a core signaling component of the MAPK kinase cascade, is often mutated in various cancers, including melanoma, lung, and colorectal cancers. The approved inhibitors were focused on targeting the BRAFV600E mutation that results in constitutive activation of kinase signaling through the monomeric protein (Class I). However, these inhibitors also paradoxically activate kinase signaling of RAF dimers, resulting in increased MAPK signaling in normal tissues. Recently, significant attention has turned to targeting RAF alterations that activate dimeric signaling (class II and III BRAF and NRAS). However, the discovery of a potent and selective inhibitor with biopharmaceutical properties suitable to sustain robust target inhibition in the clinical setting has proven challenging. Herein, we report the discovery of exarafenib (15), a highly potent and selective inhibitor that intercepts the RAF protein in the dimer compatible αC-helix-IN conformation and demonstrates anti-tumor efficacy in preclinical models with BRAF class I, II, and III and NRAS alterations.

The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients.

PURPOSE: Multiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. METHODS/MATERIALS: The KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. RESULTS: The KIM localisation accuracy was 0.2±0.9 mm (left-right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and -0.1◦±0.8◦ (left-right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. CONCLUSIONS: This work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

Is Preoperative Serum Albumin Predictive of Adverse Outcomes in Head and Neck Cancer Surgery?

BACKGROUND: Patients with head and neck cancer are at increased risk of malnutrition due to tumor burden and surgical morbidity. PURPOSE: The purpose of this study was to evaluate the association between preoperative serum albumin and 30-day adverse outcomes in patients undergoing head and neck cancer surgery. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database. Patients undergoing an ablative head and neck cancer procedure were included. Patients who had an unclear tumor location based on coding or missing outcome data were excluded. PREDICTOR VARIABLE: The primary predictor variable was preoperative albumin categorized as low (<3.4 g/dL), intermediate (3.4 to 3.9 g/dL), or high (>3.9 g/dL). OUTCOME VARIABLE: The primary outcome variable was intensive care unit (ICU)-level complications scored using the Clavien-Dindo classification system. This is a tool used to grade surgical complications, with grade IV and V complications defined as requiring ICU-level care. COVARIATES: Covariates were demographic (age, sex, body mass index), medical (smoking, functional status, weight loss), and perioperative (concurrent procedures, tumor location, reconstructive modality). ANALYSES: Descriptive, bivariate, and multiple logistic regression with bootstrap resampling statistics were used to evaluate the association between albumin and adverse outcomes. A significance level of P ≤ .05 was significant. RESULTS: A total of 4,491 subjects met inclusion criteria and had a documented albumin. There were 435 subjects with low albumin levels, 1,305 with intermediate levels, and 2,751 with high levels. In bivariate analysis, low albumin levels were associated with an increased risk of ICU-level complications, any complication, extended length of stay, and adverse discharge disposition (all P ≤ .001), while high levels were protective (all P ≤ .001). In bootstrapped multivariate analysis using intermediate albumin as the reference group and adjusting for demographics, tumor location, and reconstructive modality among others, low albumin levels were an independent predictor of ICU-level complications (P = .008, odds ratio, 1.64; 95% confidence interval, 1.14 to 2.40), while high levels were protective (P = .014, odds ratio, 0.689; 95% confidence interval, 0.521 to 0.923). CONCLUSIONS: Preoperative serum albumin was an independent predictor of adverse outcomes following ablative head and neck cancer procedures.

Anaesthesia by intravenous propofol reduces the incidence of intra-operative gastric electrical slow-wave dysrhythmias compared to isoflurane.

Gastric motility is coordinated by bioelectrical slow-wave activity, and abnormal electrical dysrhythmias have been associated with nausea and vomiting. Studies have often been conducted under general anaesthesia, while the impact of general anaesthesia on slow-wave activity has not been studied. Clinical studies have shown that propofol anaesthesia reduces postoperative nausea and vomiting (PONV) compared with isoflurane, while the underlying mechanisms remain unclear. In this study, we investigated the effects of two anaesthetic drugs, intravenous (IV) propofol and volatile isoflurane, on slow-wave activity. In vivo experiments were performed in female weaner pigs (n = 24). Zolazepam and tiletamine were used to induce general anaesthesia, which was maintained using either IV propofol (n = 12) or isoflurane (n = 12). High-resolution electrical mapping of slow-wave activity was performed. Slow-wave dysrhythmias occurred less often in the propofol group, both in the duration of the recorded period that was dysrhythmic (propofol 14 ± 26%, isoflurane 43 ± 39%, P = 0.043 (Mann-Whitney U test)), and in a case-by-case basis (propofol 3/12, isoflurane 8/12, P = 0.015 (Chi-squared test)). Slow-wave amplitude was similar, while velocity and frequency were higher in the propofol group than the isoflurane group (P < 0.001 (Student's t-test)). This study presents a potential physiological biomarker linked to recent observations of reduced PONV with IV propofol. The results suggest that propofol is a more suitable anaesthetic for studying slow-wave patterns in vivo.

Are There Differences in Opioid Prescriptions to Urban and Rural Patients by Oral and Maxillofacial Surgeons in Massachusetts From 2011 to 2021?

PURPOSE: Oral-maxillofacial surgeons (OMSs) are frequent prescribers of opioid analgesics. It remains unclear if prescription patterns differ for urban versus rural patients, given potential differences in access to and delivery of care. This study aimed to characterize urban-rural differences in opioid analgesic prescriptions to patients in Massachusetts by OMSs from 2011 to 2021. METHODS: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2011 to 2021. The primary predictor variable was patient geography (urban/rural) and secondary predictor was year (2011-2021). The primary outcome variable was milligram morphine equivalent (MME) per prescription. Secondary outcome variables were days' supply per prescription and number of prescriptions received per patient. Descriptive and linear regression statistics were performed to analyze differences in prescriptions to urban and rural patients each year and throughout the study period. RESULTS: The study data, which includes OMS opioid prescriptions (n = 1,057,412) in Massachusetts from 2011 to 2021, ranged annually between 63,678 and 116,000 prescriptions to between 58,000 and 100,000 unique patients. The cohorts each year ranged between 48 and 56% female with mean ages between 37 and 44 years. There were no differences in the mean number of patients per provider in urban and rural populations in any year. The study sample had a large majority of urban patients (>98%). MME per prescription, days' supply per prescription, and prescriptions received per patient were all generally similar between urban and rural patients each year, with the largest MME per prescription difference in 2019 (87.3 for rural to 73.9 for urban patients, P < .01). From 2011 to 2021, all patients had a steady decrease in MME per prescription (ß = -6.64, 95% confidence interval: -6.81, -6.48; R2 = 0.39) and day's supply per prescription (ß = -0.1, 95% confidence interval: -0.1, -0.09; R2 = 0.37). CONCLUSION: In Massachusetts, there were similar opioid prescribing patterns by oral and maxillofacial surgeons to urban and rural patients from 2011 to 2021. There has also been a steady decrease in the duration and total dosage of opioid prescriptions to all patients. These results are consistent with multiple statewide policies over the last several years aimed at curbing opioid overprescribing.

Predictive and robust gene selection for spatial transcriptomics.

A prominent trend in single-cell transcriptomics is providing spatial context alongside a characterization of each cell's molecular state. This typically requires targeting an a priori selection of genes, often covering less than 1% of the genome, and a key question is how to optimally determine the small gene panel. We address this challenge by introducing a flexible deep learning framework, PERSIST, to identify informative gene targets for spatial transcriptomics studies by leveraging reference scRNA-seq data. Using datasets spanning different brain regions, species, and scRNA-seq technologies, we show that PERSIST reliably identifies panels that provide more accurate prediction of the genome-wide expression profile, thereby capturing more information with fewer genes. PERSIST can be adapted to specific biological goals, and we demonstrate that PERSIST's binarization of gene expression levels enables models trained on scRNA-seq data to generalize with to spatial transcriptomics data, despite the complex shift between these technologies.

Delayed Gastric Emptying and Gastric Remnant Function After Pancreaticoduodenectomy: A Systematic Review of Objective Assessment Modalities.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD). The diagnosis of DGE is based on International Study Group for Pancreatic Surgery (ISGPS) clinical criteria and objective assessments of DGE are infrequently used. The present literature review aimed to identify objective measures of DGE following PD and determine whether these measures correlate with the clinical definition of DGE. METHODS: A systematic search was performed using the MEDLINE Ovid, EMBASE, Google Scholar and CINAHL databases for studies including pancreatic surgery, delayed gastric emptying and gastric motility until June 2022. The primary outcome was modalities undertaken for the objective measurement of DGE following PD and correlation between objective measurements and clinical diagnosis of DGE. Relevant risk of bias analysis was performed. RESULTS: The search revealed 4881 records, of which 46 studies were included in the final analysis. There were four objective modalities of DGE assessment including gastric scintigraphy (n = 28), acetaminophen/paracetamol absorption test (n = 10), fluoroscopy (n = 6) and the 13C-acetate breath test (n = 3). Protocols were inconsistent, and reported correlations between clinical and objective measures of DGE were variable; however, amongst these measures, at least one study directly or indirectly inferred a correlation, with the greatest evidence accumulated for gastric scintigraphy. CONCLUSION: Several objective modalities to assess DGE following PD have been identified and evaluated, however are infrequently used. Substantial variability exists in the literature regarding indications and interpretation of these tests, and there is a need for a real-time objective modality which correlates with ISGPS DGE definition after PD.

Interfacility Emergency Department Transfer for Midface Fractures in the United States.

PURPOSE: Interfacility hospital transfer for isolated midfacial fractures is common but rarely clinically necessary. The purpose of this study was to generate nationally representative estimates regarding the incidence, risk factors, and cost of transfer for isolated midface fractures. METHODS: This was a retrospective cohort study using the Nationwide Emergency Department Sample 2018 to identify patients with isolated midface fractures. The primary predictor variable was hospital trauma center designation (Level I, Level II, Level III, and nontrauma center). The primary outcome variable was hospital transfer. Total emergency department (ED) charges were also assessed. Covariates were demographic, medical, injury-related, and hospital characteristics. Descriptive, bivariate, and multiple logistic regression statistics were used to evaluate the incidence and predictors of interfacility transfer. RESULTS: During the study period, there were 161,022 ED encounters with a midface fracture as primary diagnosis, of which 5,680 were transferred (3.53%). In an unadjusted analysis, evaluation at a nontrauma center, level III trauma center, nonteaching hospital, and numerous demographic, medical, and injury-related variables were associated with transfer (P ≤ .001). In the adjusted model, the strongest independent predictors for hospital transfer were evaluation at a nontrauma center (odds ratio [OR] = 16.2, 95% confidence interval [CI] = 13.6-19.4), level III trauma center (OR = 13.4, 95% CI = 11.1-16.1) or level II trauma center (OR = 3.25, 95% CI = 2.66-3.98), any Le Fort fracture (OR = 12.0, 95% CI = 10.4-14.0), orbital floor fracture (OR = 3.73, 95% CI = 3.48-4.00), history of cerebrovascular event (OR = 2.74, 95% CI = 2.18-3.45), and cervical spine injury (OR = 5.87, 95% CI = 4.79-7.20) (P ≤ .001). The average ED charge per encounter was $7,206 ± 9,294 for a total nationwide charge of approximately 1.16 billion dollars. Transferred subjects had total ED charges of $97 million, not including additional charges at the recipient hospital. CONCLUSION: Isolated midface fractures are transferred infrequently, but given the high incidence have substantial healthcare costs. Predictors of transfer were mixed rather than clustered within one variable type, although it is likely that transfers are driven in part by lack of access to maxillofacial specialists given the predominance of hospital covariates. Programs evaluating necessity of transfer and facilitating specialist evaluation in the outpatient setting may reduce healthcare expenditures for these injuries.