Low Socioeconomic Indicators Correlate with Critical Pre-Operative Glenoid Bone Loss and Care Delays.

BACKGROUND: Chronic and recurrent shoulder dislocations prior to stabilization can increase the risk of glenoid bone loss. Glenoid bone loss exceeding critical levels can lead to further instability and decreased outcomes following arthroscopic labral repair. Indicators of low socioeconomic status (SES), such as high Area Deprivation Index (ADI) and non-commercial insurance, are related to generalized delays to orthopedic care, which can cause recurrent instability and increase glenoid bone loss. HYPOTHESIS/PURPOSE: Higher national ADI and non-commercial insurance would be associated with greater levels of radiographic glenoid bone loss after glenoid instability. METHODS: A retrospective study was performed with patients who underwent anterior labral repair. Chart review included demographics, course of care data, preoperative instability data, national ADI, and insurance status. The Neighborhood Atlas Website and patients' home addresses were used to obtain national ADI. Glenoid bone loss was measured using the Best-fit circle Pico method on three-dimensionally aligned magnetic resonance images (MRIs). Researchers were blinded to SES indicators during radiographic analysis. Glenoid bone loss was compared between SES indicators using one-way ANOVAs. RESULTS: 146 patients met inclusion criteria and had complete datasets (23.3% female; 22.4±7.0-years-old; national ADI=16.1±15.3). Patients experienced on average 9.12±6.63% glenoid bone loss. A curve fitting tool determined a quadratic non-linear regression best characterized the association of glenoid bone loss and ADI (R2 = 0.392, p < 0.001). Individuals with commercial insurance experienced 8.58%±6.69% glenoid bone loss as compared to 11.78%±6.30% in individuals with Medicaid insurance (p=0.03). Critical bone loss at a threshold of 13.5% was more likely with higher national ADI (p<0.001) and Medicaid insurance (OR=2.49, CI=1.02-6.09). However, only national ADI was predictive of subcritical bone loss at a threshold of 10% (p<0.001). CONCLUSION: Patients with greater national ADI and Medicaid insurance status had greater rates of critical preoperative glenoid bone loss at a threshold of 13.5%. Greater national ADI is also predictive of subcritical glenoid bone loss at a threshold of 10% and overall glenoid bone loss. Further study is needed to assess the postoperative implications of these findings in this population.

Anatomic restoration of lateral humeral offset and humeral retroversion optimizes functional outcomes following reverse total shoulder arthroplasty.

Cadaveric and computer simulations suggest lateral humeral offset (LHO) and humeral retroversion (HR) are associated with strength and range of motion (ROM) after reverse total shoulder arthroplasty (rTSA), butin vivodata is lacking. This study aimed to evaluate the effects of implant parameters (i.e. LHO and HR) on strength and ROM. LHO and HR were measured using pre-operative and post-operative computed tomography (CT) scans. Postoperative strength was measured across three planes of motion using a Biodex isokinetic dynamometer. Postoperative active and passive ROM during forward elevation, external rotation (ER), and internal rotation (IR) were assessed using a goniometer or spinal level. 30 rTSA patients (14 M, 16F, age: 71.8 ± 6.7yrs) participated with an average postoperative follow-up of 2.4 ± 1.1 years. Regarding strength, higher post-op LHO values were predictive of greater postoperative strength across all movements. However, lateralization of the implant beyond pre-op values (i.e. post-op LHO > pre-op LHO) was associated with poorer strength performance across all ranges of motion. Similar to strength outcomes, greater deviations from pre-op LHO was predictive of poorer IR ROM. Lastly, patients with minimal deviations in HR (post-op HR within 10° of pre-op HR) and minimal deviations in LHO (post-op LHO ≤ pre-op LHO) displayed the greatest postoperative ER ROM. Anatomic restoration of LHO combined with anatomic restoration of HR may be ideal for maximizing strength and ROM following rTSA. Overlateralization beyond anatomic may have negative consequences. Optimal implant lateralization and version may need to be individualized based on preoperative values.

TWINKLE: An open-source two-photon microscope for teaching and research.

Many laboratories use two-photon microscopy through commercial suppliers, or homemade designs of considerable complexity. The integrated nature of these systems complicates customization, troubleshooting as well as grasping the principles of two-photon microscopy. Here, we present "Twinkle": a microscope for Two-photon Imaging in Neuroscience, and Kit for Learning and Education. It is a fully open, high-performance and cost-effective research and teaching microscope without any custom parts beyond what can be fabricated in a university machine shop. The instrument features a large field of view, using a modern objective with a long working distance and large back aperture to maximize the fluorescence signal. We document our experiences using this system as a teaching tool in several two week long workshops, exemplify scientific use cases, and conclude with a broader note on the place of our work in the growing space of open-source scientific instrumentation.

Links between climatic histories and the rise and fall of a Pacific chiefdom.

Sea level rise and climate change are shaping present societies, particularly those on oceanic islands. Few historical examples could serve as references for these changes. One such potential model is the Saudeleur Dynasty with its capital Nan Madol on the Pacific Island of Pohnpei. However, the timing of its construction, as well as the dynasty's fluctuations and potential environmental influences, has remained unresolved. Through the analyses of 230Th ages on 171 dates on corals fragments used as building materials and charcoal 14C ages from excavations, 2 major construction phases spanning from the 10th to the 15th century CE can be discerned. The results show that the first phase of the site's construction, spanning the 10th-12th century, marked the dynasty's rise. The second period, spanning from the late 12th to the early 15th century, provides the most substantial evidence for the demise of the island-scale chiefdom and a significant societal reorganization. The phases are centuries earlier than previously believed. With this new evidence, we propose the hypothesis that variations in the El Niño-Southern Oscillation and subsidence-related sea level rise presented major challenges for building and maintaining Nan Madol, and thus, influenced the course of the island's history. This case serves as a compelling example of how adverse climatic conditions can spur investments-in this case, in seawater defense under high sea levels-yet ultimately may contribute to abandonment. It offers lessons for island nations, showcasing coastal resilience in the face of worsening catastrophic events that unfolded over generations.

Network statistics of the whole-brain connectome of Drosophila.

Brains comprise complex networks of neurons and connections, similar to the nodes and edges of artificial networks. Network analysis applied to the wiring diagrams of brains can offer insights into how they support computations and regulate the flow of information underlying perception and behaviour. The completion of the first whole-brain connectome of an adult fly, containing over 130,000 neurons and millions of synaptic connections1-3, offers an opportunity to analyse the statistical properties and topological features of a complete brain. Here we computed the prevalence of two- and three-node motifs, examined their strengths, related this information to both neurotransmitter composition and cell type annotations4,5, and compared these metrics with wiring diagrams of other animals. We found that the network of the fly brain displays rich-club organization, with a large population (30% of the connectome) of highly connected neurons. We identified subsets of rich-club neurons that may serve as integrators or broadcasters of signals. Finally, we examined subnetworks based on 78 anatomically defined brain regions or neuropils. These data products are shared within the FlyWire Codex ( https://codex.flywire.ai ) and should serve as a foundation for models and experiments exploring the relationship between neural activity and anatomical structure.

Shoulder Periprosthetic Joint Infection: Principles of Prevention, Diagnosis, and Treatment.

➢ Shoulder periprosthetic joint infection (PJI) is a potentially devastating complication after arthroplasty and is projected to rise with increasing numbers of performed arthroplasties, particularly reverse shoulder arthroplasties.➢ Important considerations for the diagnosis and treatment of shoulder PJI include age, sex, implant type, primary compared with revision shoulder surgery, comorbidities, and medications (i.e., corticosteroids and disease-modifying antirheumatic drugs).➢ Diagnosis and management are unique compared with lower-extremity PJI due to the role of lower-virulence organisms in shoulder PJI, specifically Cutibacterium acnes.➢ Treatment pathways depend on chronicity of infection, culture data, and implant type, and exist on a spectrum from irrigation and debridement to multistage revision with temporary antibiotic spacer placement followed by definitive revision arthroplasty.

Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Editorial Commentary: Arthroscopic Superior Capsular Reconstruction Acts as a Biologic Spacer by Increasing Acromiohumeral Distance.

Massive rotator cuff tears can be successfully treated with a wide variety of surgical procedures depending on many patient factors. The arthroscopic superior capsular reconstruction (SCR) is a good procedure for a younger patient with pseudoparesis, no lag signs, and a primary complaint of pain. How does the SCR work to achieve a good clinical outcome? One theory is that it restores the force couple and normal kinematics of the shoulder, but more evidence supports the theory that it acts as a biologic spacer. Differences in success of autograft versus allograft is likely due to graft thickness. Recent studies have shown that 6- to 8-mm fascia lata autograft has better outcomes than 2- to 4-mm dermal allograft. Improving the acromiohumeral distance and tissue healing to the tuberosity is important because this may prevent painful impingement. In our experience, when a patient has painful impingement and preserved motion or pseudoparesis, we will routinely offer a soft tissue procedure that can increase the acromiohumeral distance, acting as a spacer to prevent the greater tuberosity from contacting the acromion.

Rehabilitation and Return to Sport following Operative and Nonoperative Treatment of Anterior Shoulder Instability.

There has been growing interest in the rehabilitation process and timing of returning an athlete to sport following the management options for anterior shoulder instability. The purpose of this article is to review the current rehabilitation and return to sport (RTS) protocols for various nonoperative and operative management strategies following anterior shoulder instability events. When appropriate in the rehabilitation protocol, RTS testing should be criteria based, rather than time based, with a special focus given to psychological readiness in order to promote successful return to athletics and prevention of recurrent instability episodes in the future.

Shoulder Injury Incidence and Epidemiology in Youth, High School, and Collegiate Fastpitch Softball Players: A Systematic Review and Future Research Perspectives.

CONTEXT: Fastpitch softball is one of the most popular sports in the United States among young female athletes. Softball players regularly subject their shoulders to extreme range of motion and high velocity movements. To date, no systematic review has reported on the epidemiology and incidence of shoulder injuries in softball players. OBJECTIVE: To describe the incidence and epidemiology of softball-related shoulder injuries in youth, high school, and collegiate female softball players. DATA SOURCES: PubMed, Web of Science, and Embase were searched for relevant English language articles from 1980 to 2023. STUDY SELECTION: Studies selected based on predefined inclusion criteria. Studies were required to be available full text, in English. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: A preliminary screening was performed based on study title and abstract. In the subsequent screening, the full text versions of the remaining articles were evaluated by 2 reviewers for the fulfillment of the inclusion criteria. RESULTS: A total of 7 articles met criteria for inclusion. All studies evaluated injuries among softball players for at least 1 season. In total, there were 1107 softball-related shoulder injuries reported in the 7 studies included in this systematic review. Of the 3 studies that included a shoulder injury rate, a mean rate of 4.01 shoulder injuries per 10,000 athlete-exposures was calculated. The 2 most common shoulder injuries were shoulder muscle-tendon strains (297) and shoulder/biceps tendinitis (220). CONCLUSION: High-level prospective studies reporting injury incidence and risk factors among female softball players are extremely limited. Only 2 studies eligible for inclusion in this systematic review were prospective in nature, with neither of these reporting the specific injury rate for shoulder injuries among softball players.

Surgical Parameters During Reverse Shoulder Arthroplasty Predict Post-Surgical Kinematics During the Hand-to-Head Motion.

PURPOSE: This study aimed to identify surgical parameters during reverse shoulder arthroplasty (RSA) that predict post-surgical kinematics during the hand-to-head motion (H2H) and to identify associations between kinematics and outcomes. We hypothesized that greater humeral retroversion and lateralization predict kinematics, and that more scapular upward rotation is associated with better PROs and more range of motion (ROM). METHODS: Thirty-five post-RSA patients consented to participate. All surgical parameters were recorded while operating or measured on CT. Participants performed H2H while synchronized biplane radiographs were collected at 50 images/second. Digitally reconstructed radiographs were matched to biplane radiographs to determine glenohumeral and scapular kinematics. For all rotations, the contribution, end position, peak angles, and ROM were calculated. Contact path between the glenosphere and polyethylene insert was calculated. Patient-reported outcomes (PROs), clinical ROM, and strength were measured. Multiple linear regression identified surgical parameters that predicted kinematics, and Pearson correlation identified associations between kinematics and outcomes. RESULTS: Less humeral retroversion predicted greater peak abduction (p = 0.035). Humeral neck-shaft angle, retroversion, and glenoid tilt predicted the peak posterior contact path (p = 0.012). Better PROs were associated with more superior contact path (p < 0.001), more abduction (p < 0.001), and greater peak scapular upward rotation (p = 0.017). Greater strength was correlated with more peak external rotation (p = 0.035). Greater external rotation at 90º was associated with more abduction (p = 0.008) and upward scapula rotation ROM (p = 0.015) during H2H. CONCLUSION: Less humeral retroversion predicted kinematics during H2H that were associated with more favorable PROs and clinical outcomes.

Bioaugmentation demonstrates similar outcomes and failure rates for arthroscopic revision rotator cuff repair compared to revision without bioaugmentation.

Background: Arthroscopic revision rotator cuff repairs (RCRs) exhibit lower healing rates and inferior outcomes compared to primary repairs. There is limited evidence regarding the use of bioaugmentation in the setting of revision RCRs. Autologous conditioned plasma (ACP) is a promising adjunct that has been shown to improve healing rates and patient-reported outcomes (PROs) in the primary setting. In addition, bioinductive patches such as collagen bovine patches have become a popular adjunct for stimulating healing in the primary setting. The aim of this study is to assess the outcomes after use of ACP and collagen bovine patch augmentation for revision arthroscopic RCR. We hypothesized improved PROs and higher healing rates would be observed with bioaugmentation for revision repair compared to without. Methods: This was an institutional review board-approved, retrospective case-control study from 2 fellowship-trained surgeons that included all consecutive patients undergoing arthroscopic revision RCR from 2010 to 2021. Reconstruction such as superior capsular reconstruction, partial revision repair, and less than 1-year follow-up were excluded. The bioaugmentation cohort received ACP and/or collagen bovine patch at the time of revision repair. PROs were collected from all patients including American Shoulder and Elbow Surgeons Standardized Assessment Form (ASES), visual analog scale for pain (VAS), Brophy score, and Patient-Reported Outcomes Measurement Information System (PROMIS) mental and physical scores. Failure of revision RCR was defined as an ASES postoperative total score less than 60 or a symptomatic retear confirmed on magnetic resonance imaging. Student's t-test was used for all comparisons of continuous variables. Chi-squared test used for comparison of all categorical variables. Statistical significance was set at <0.05. Results: Thirty-eight patients met inclusion criteria with average follow-up of 3.5 ± 1.7 years. There was no significant difference in follow-up between patients with and without bioaugmentation. Of the 38 patients, 14 patients met failure criteria. There was no significant difference in the rate of failure between the bioaugmentation cohort (6/19, 31.6%) vs. patients who did not receive bioaugmentation (8/19, 42.1%) (P = .74). In addition, no significant differences were identified for ASES (64.6 ± 20.1 vs. 57.5 ± 17.2, P = .32), Brophy (6.4 ± 5.2 vs. 6.0 ± 4.1, P = .84), PROMIS Mental (13.4 ± 3.9 vs. 11.7 ± 3.2), or PROMIS Physical (12.8 ± 3.1 vs. 11.9 ± 3.2) scores between the bioaugmentation vs. no bioaugmentation groups. Conclusion: Bioaugmentation with a bioinductive collagen patch or ACP demonstrated similar failure and PROs compared to without bioaugmentation in the setting of revision RCR.

Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Scapular morphology does not predict supraspinatus tendon tear propagation following an individualised exercise therapy programme.

Purpose: To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical shoulder angle (CSA) and type III acromial morphology predict a positive change in tear size. Methods: Fifty-nine individuals aged 40-70 years with isolated symptomatic high-grade partial or full-thickness supraspinatus tendon tears were included. Individuals participated in a structured, individualised 12-week exercise therapy programme and underwent ultrasound to measure tear size at baseline and 12 months following therapy. Computed tomography images were segmented to create three-dimensional subject-specific bone models and reviewed by three trained clinicians to measure CSA and to determine acromion morphology based on the Bigliani classification. A binary logistic regression was performed to determine the predictive value of CSA and acromion morphology on tear propagation. Results: The CSA was 30.0 ± 5.4°. Thirty-one individuals (52.5%) had type II acromial morphology, followed by type III and type I morphologies (25.4% and 22.0%, respectively); 81.4% experienced no change in tear size, four (6.8%) individuals experienced tear propagation and seven (11.9%) individuals had a negative change in tear size. No significant difference in tear propagation rates based on CSA or acromion morphology (not significant [NS]) was observed. The model predicted tear size status in 81.4% of cases but only predicted tear propagation 8.3% of the time. Overall, CSA and acromion morphology only predicted 24.3% (R 2 = 0.243) of variance in tear propagation (NS). Conclusions: CSA and acromion morphology were NS predictors of tear propagation of the supraspinatus tendon 12 months following an individualised exercise therapy programme. Level of Evidence: II.

Design considerations for protective boots for first responders to hazardous materials incidents.

First responder professionals are at high risk for work-related injuries (e.g., extreme temperatures, chemical and biological threats); boots are essential to ensure body protection since they have full contact with the ground in all scenarios. A substantial body of work has investigated the necessity of improvements in protective boots, but there is limited research conducted on boots with fit-adjustable fasteners for secure and adjustable fit within this context. Thus, this study explored the areas for improvement in boot design for the development of form-fitting and yet comfortable boots focusing on two different boot designs, prototype all-hazards tactical boots (lace-up) and rubber boots (slip-on). Findings indicated that the boot design should address participants' concerns with the material choices of boots, specifically with bulkiness, weight, and flexibility. Our findings provide insights into boot material and design choices to improve protective boots for first responders.

Total Shoulder Arthroplasty is associated With Less Pain and Better Functional Outcomes, but Humeral Head Resurfacing may be Preferred in Younger, Higher Demand Patients: A Short-Term Outcomes Study in Patients with Glenohumeral Osteoarthritis.

Objectives: This study aimed to compare short-term outcomes following Total Shoulder Arthroplasty (TSA) and Humeral Head Resurfacing (HHR) in patients with glenohumeral osteoarthritis (GHOA). Methods: A retrospective analysis included patients who had undergone either TSA or HHR for GHOA at a single institution. Baseline demographics, complications, range of motion (active forward flexion, FF and active external rotation, ER), visual analog scores (VAS), and Subjective Shoulder Values (SSV) were collected. Results: A total of 69 TSA and 56 HHR patients were analyzed. More HHR patients were laborers (44% versus 21%, P=0.01). There were more smokers in the TSA group (25% versus 11%, P=0.04) and more cardiovascular disease in the HHR cohort (64% versus. 6%, p<0.0001). Postoperative FF was similar, but ER was greater in the HHR (47° ± 15°) vs. TSA group (40° ± 12°, P = 0.01). VAS was lower after TSA vs. HHR (median 0, IQR 1 versus median 3.7, IQR 6.9, p<0.0001), and SSV was higher after TSA (89% ± 13% vs. 75% ± 20% after HHR; p<0.0001). Post-operative impingement was more common after HHR (32% vs. 3% for TSA, p<0.0001). All other complications were equivalent. Conclusion: While younger patients and heavy laborers had improved ER following HHR, their pain relief was greater after TSA. Decisions on surgical technique should be based on patient-specific demographic and anatomic factors.

Arthroscopic Bankart repair with remplissage yields similar outcomes to open Latarjet for primary and revision stabilization in the setting of subcritical glenoid bone loss.

BACKGROUND: Management of patients with recurrent anterior glenohumeral instability in the setting of subcritical glenoid bone loss (GBL), defined in this study as 20% GBL or less, remains controversial. This study aimed to compare arthroscopic Bankart with remplissage (ABR + R) to open Latarjet for subcritical GBL in primary or revision procedures. We hypothesized that ABR + R would yield higher rates of recurrent instability and reoperation compared to Latarjet in both primary and revision settings. METHODS: A retrospective study was conducted on patients undergoing either arthroscopic ABR + R or an open Latarjet procedure. Patients with connective tissue disorders, critical GBL (>20%), <2 year follow-up, or insufficient data were excluded. Recurrent instability and revision were the primary outcomes of interest. Additional outcomes of interest included subjective shoulder value, strength, and range of motion (ROM) RESULTS: One hundred eight patients (70 ABR + R, 38 Latarjet) were included with an average follow-up of 4.3 ± 2.1 years. In the primary and revision settings, similar rates of recurrent instability (Primary: P = .60; Revision: P = .28) and reoperation (Primary: P = .06; Revision: P = 1.00) were observed between Latarjet and ABR + R. Primary ABR + R exhibited better subjective shoulder value, active ROM, and internal rotation strength compared to primary open Latarjet. However, no differences were observed in the revision setting. CONCLUSION: Similar rates of recurrent instability and reoperation in addition to comparable outcomes with no differences in ROM were found for ABR + R and Latarjet in patients with subcritical GBL in both the primary and revision settings. ABR + R can be a safe and effective procedure in appropriately selected patients with less than 20% GBL for both primary and revision stabilization.

Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.

BACKGROUND: The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. METHODS: A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. RESULTS: A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2 ms vs. 8.9 ± 32.6 ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2 ms vs. 24.0 ± 25.1 ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (- 7.5 ± 8.7 bpm vs. - 8.5 ± 13.9 bpm vs. - 8.3 ± 13.2 bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36 days vs. 4.2 ± 1.0 days, p < 0.0001). CONCLUSION: IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias.

Phenotyping Hepatic Immune-Related Adverse Events in the Setting of Immune Checkpoint Inhibitor Therapy.

PURPOSE: We present and validate a rule-based algorithm for the detection of moderate to severe liver-related immune-related adverse events (irAEs) in a real-world patient cohort. The algorithm can be applied to studies of irAEs in large data sets. METHODS: We developed a set of criteria to define hepatic irAEs. The criteria include: the temporality of elevated laboratory measurements in the first 2-14 weeks of immune checkpoint inhibitor (ICI) treatment, steroid intervention within 2 weeks of the onset of elevated laboratory measurements, and intervention with a duration of at least 2 weeks. These criteria are based on the kinetics of patients who experienced moderate to severe hepatotoxicity (Common Terminology Criteria for Adverse Events grades 2-4). We applied these criteria to a retrospective cohort of 682 patients diagnosed with hepatocellular carcinoma and treated with ICI. All patients were required to have baseline laboratory measurements before and after the initiation of ICI. RESULTS: A set of 63 equally sampled patients were reviewed by two blinded, clinical adjudicators. Disagreements were reviewed and consensus was taken to be the ground truth. Of these, 25 patients with irAEs were identified, 16 were determined to be hepatic irAEs, 36 patients were nonadverse events, and two patients were of indeterminant status. Reviewers agreed in 44 of 63 patients, including 19 patients with irAEs (0.70 concordance, Fleiss' kappa: 0.43). By comparison, the algorithm achieved a sensitivity and specificity of identifying hepatic irAEs of 0.63 and 0.81, respectively, with a test efficiency (percent correctly classified) of 0.78 and outcome-weighted F1 score of 0.74. CONCLUSION: The algorithm achieves greater concordance with the ground truth than either individual clinical adjudicator for the detection of irAEs.

Minimal important clinical difference values are not uniformly valid in the active duty military population recovering from shoulder surgery.

BACKGROUND: There are multiple methods for calculating the minimal clinically important difference (MCID) threshold, and previous reports highlight heterogeneity and limitations of anchor-based and distribution-based analyses. The Warfighter Readiness Survey assesses the perception of a military population's fitness to deploy and may be used as a functional index in anchor-based MCID calculations. The purpose of the current study in a physically demanding population undergoing shoulder surgery was to compare the yields of 2 different anchor-based methods of calculating MCID for a battery of PROMs, a standard receiver operating characteristic (ROC) curve-based MCIDs and baseline-adjusted ROC curve MCIDs. METHODS: All service members enrolled prospectively in a multicenter database with prior shoulder surgery that completed pre- and postoperative PROMs at a minimum of 12 months were included. The PROM battery included Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Patient Reported Outcome Management Information System (PROMIS) physical function (PF), PROMIS pain interference (PI), and the Warfighter Readiness Survey. Standard anchor-based and baseline-adjusted ROC curve MCIDs were employed to determine if the calculated MCIDs were both statistically and theoretically valid (95% confidence interval [CI] either completely negative or positive). RESULTS: A total of 117 patients (136 operations) were identified, comprising 83% males with a mean age of 35.7 ± 10.4 years and 47% arthroscopic labral repair/capsulorrhaphy. Using the standard, anchor-based ROC curve MCID calculation, the area under the curve (AUC) for SANE, ASES, PROMIS PF, and PROMIS PI were greater than 0.5 (statistically valid). For ASES, PROMIS PF, and PROMIS PI, the calculated MCID 95% CI all crossed 0 (theoretically invalid). Using the baseline-adjusted ROC curve MCID calculation, the MCID estimates for SANE, ASES, and PROMIS PI were both statistically and theoretically valid if the baseline score was less than 70.5, 69, and 65.7. CONCLUSION: When MCIDs were calculated and anchored to the results of standard, anchor-based MCID, a standard ROC curve analysis did not yield statistically or theoretically valid results across a battery of PROMs commonly used to assess outcomes after shoulder surgery in the active duty military population. Conversely, a baseline-adjusted ROC curve method was more effective at discerning changes across a battery of PROMs among the same cohort.