The Tightrope Study: A cadaveric, biomechanical comparison of generations of suspensory fixation with internal brace for Rockwood grade V AC joint injuries.

BACKGROUND: Surgical treatment of Rockwood grade V AC joint injuries remains varied. We hypothesized that the addition of a second suspensory device between the clavicle and coracoid would yield superior biomechanical results over a single device. We also hypothesized that the addition of an internal brace across the AC joint to a suspensory device would yield superior results over the suspensory device in isolation. METHODS: A total of 24 cadaveric shoulders were dissected and randomized to four groups with four different constructs implanted: Group A: Single AC TightRope (Arthrex Inc., Naples, FL, USA) Group B: Double AC TightRope Group C: Single Knotless AC TightRope (Arthrex Inc., Naples, FL, USA) Group D: Single Knotless AC TightRope with AC InternalBrace Ligament Augmentation (Arthrex Inc., Naples, FL, USA) These were then loaded in the Robotic arm (SIMVITRO) where 250 cycles of 50N of force in the superior plane was applied. Dynamic creep, displacement, translation and stiffness were assessed. RESULTS: Testing was successfully completed for all specimens. There were no failures due to fracture or translation of the clavicle greater than 5mm from the starting position. Reduction was maintained with a mean superior displacement of 1.7 mm (± 1.4 mm). The mean peak to peak displacement, superior and posterior translation, dynamic creep and stiffness did not differ significantly between construct groups. CONCLUSION: This study did not demonstrate any significant biomechanical differences between groups in terms of displacement, translation, creep or stiffness.

ChatGPT performance on the American Shoulder and Elbow Surgeons maintenance of certification exam.

BACKGROUND: While multiple studies have tested the ability of large language models (LLMs), such as ChatGPT, to pass standardized medical exams at different levels of training, LLMs have never been tested on surgical sub-specialty examinations, such as the American Shoulder and Elbow Surgeons (ASES) Maintenance of Certification (MOC). The purpose of this study was to compare results of ChatGPT 3.5, GPT-4, and fellowship-trained surgeons on the 2023 ASES MOC self-assessment exam. METHODS: ChatGPT 3.5 and GPT-4 were subjected to the same set of text-only questions from the ASES MOC exam, and GPT-4 was additionally subjected to image-based MOC exam questions. Question responses from both models were compared against the correct answers. Performance of both models was compared to corresponding average human performance on the same question subsets. One sided proportional z-test were utilized to analyze data. RESULTS: Humans performed significantly better than Chat GPT 3.5 on exclusively text-based questions (76.4% vs. 60.8%, P = .044). Humans also performed significantly better than GPT 4 on image-based questions (73.9% vs. 53.2%, P = .019). There was no significant difference between humans and GPT 4 in text-based questions (76.4% vs. 66.7%, P = .136). Accounting for all questions, humans significantly outperformed GPT-4 (75.3% vs. 60.2%, P = .012). GPT-4 did not perform statistically significantly betterer than ChatGPT 3.5 on text-only questions (66.7% vs. 60.8%, P = .268). DISCUSSION: Although human performance was overall superior, ChatGPT demonstrated the capacity to analyze orthopedic information and answer specialty-specific questions on the ASES MOC exam for both text and image-based questions. With continued advancements in deep learning, LLMs may someday rival exam performance of fellowship-trained surgeons.

Midterm follow-up of the Nexel total elbow arthroplasty.

BACKGROUND: Aseptic loosening is one of the most common complications of total elbow arthroplasty (TEA). Modern implants, such as the Nexel, have been designed in an attempt to decrease loosening. The present study aims to report implant survivorship, radiographic assessment of loosening and lucency, and patient-reported outcome measures (PROMs) in patients treated with the Nexel TEA at midterm follow-up. METHODS: Consecutive series of adult patients underwent TEA using the Nexel by a single surgeon via standardized technique. Patients with minimum 3-year follow-up with radiographic and PROM data were included. Survivorship was defined by the absence of revision. Loosening was assessed via the Wrightington method by 3 independent fellowship-trained shoulder and elbow surgeons. Lucency was analyzed across individual radiographic zones on orthogonal radiographs. PROMs included the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), Patient-Rated Elbow Evaluation (PREE), and EuroQoL-5 Dimensions (EQ-5D). RESULTS: Thirty-eight consecutive patients (22 female, 16 male) with a mean age of 67 years underwent TEA via a triceps-sparing isolated medial window approach. Mean follow-up was 5.5 years (range 3-9). Primary diagnoses were as follows: 19 osteoarthritis (OA), 9 rheumatoid arthritis (RA), 9 post-traumatic arthritis (PA), and 1 conversion of elbow arthrodesis. Overall survivorship was 97.4%, with 1 patient undergoing revision for infection. Loosening was found in 5.3% of elbows, averaged across 3 observers. Lucency was most pronounced at the level of the humeral condyles. PROMs demonstrated significant and clinically meaningful improvements in 76%, 92%, and 73% of patients for QuickDASH, PREE, and EQ-5D, respectively. No significant correlations were found between patient age, gender, loosening, lucency, and PROMs. CONCLUSION: At midterm follow-up, the Nexel TEA demonstrated excellent overall survivorship and low rate of implant loosening. The single failure requiring revision for infection was conversion of a prior elbow arthrodesis. PROMs overall exhibited marked and consistent improvement from preoperative to final postoperative follow-up. Although promising, these results should be interpreted with some caution as long-term data regarding this prosthesis are still lacking.

Modern Treatment of Neurogenic Thoracic Outlet Syndrome: Pathoanatomy, Diagnosis, and Arthroscopic Surgical Technique.

Compressive pathology in the supraclavicular and infraclavicular fossae is broadly termed "thoracic outlet syndrome," with the large majority being neurogenic in nature. These are challenging conditions for patients and physicians and require robust knowledge of thoracic outlet anatomy and scapulothoracic kinematics to elucidate neurogenic versus vascular disorders. The combination of repetitive overhead activity and scapular dyskinesia leads to contracture of the scalene muscles, subclavius, and pectoralis minor, creating a chronically distalized and protracted scapular posture. This decreases the volume of the scalene triangle, costoclavicular space, and retropectoralis minor space, with resultant compression of the brachial plexus causing neurogenic thoracic outlet syndrome. This pathologic cascade leading to neurogenic thoracic outlet syndrome is termed pectoralis minor syndrome when primary symptoms localize to the infraclavicular area. Making the correct diagnosis is challenging and requires the combination of complete history, physical examination, advanced imaging, and ultrasound-guided injections. Most patients improve with nonsurgical treatment incorporating pectoralis minor stretching and periscapular and postural retraining. Surgical decompression of the thoracic outlet is reserved for compliant patients who fail nonsurgical management and respond favorably to targeted injections. In addition to prior exclusively open procedures with supraclavicular, infraclavicular, and/or transaxillary approaches, new minimally invasive and targeted endoscopic techniques have been developed over the past decade. They involve the endoscopic release of the pectoralis minor tendon, with additional suprascapular nerve release, brachial plexus neurolysis, and subclavius and interscalene release depending on the preoperative work-up.

Modern Treatment of Cubital Tunnel Syndrome: Evidence and Controversy.

Cubital tunnel syndrome is the second most common peripheral mononeuropathy in the upper extremity. However, the diagnosis and treatment of cubital tunnel syndrome remains controversial without a standard algorithm. Although diagnosis can often be made from the patient's history and physical examination alone, electrodiagnostic studies, ultrasound, computed tomography (CT), and magnetic resonance image (MRI) can also be useful in diagnosing the disease and selecting the most appropriate treatment option. Treatment options include conservative nonoperative techniques as well as various surgical options, including in situ decompression with or without transposition, medial epicondylectomy, and nerve transfer in advanced disease. The purpose of this review is to summarize the most up-to-date literature regarding cubital tunnel syndrome and propose a treatment algorithm to provide clarity about the challenges of treating this complex patient population.

Trends and projections in surgical stabilization of glenohumeral instability in the United States from 2009 to 2030: rise of the Latarjet procedure and fall of open Bankart repair.

BACKGROUND: Advances in surgical techniques have improved the ability to address recurrent glenohumeral instability via arthroscopic capsulolabral repair and bone-restoring procedures such as the Latarjet procedure. Given the paucity of studies analyzing temporal trends in the surgical management of glenohumeral instability, the purpose of this study was to assess trends in the treatment of anterior, posterior, and multidirectional instability over a 10-year period and model projections to 2030. METHODS: Using the IBM Watson MarketScan national database, we identified all patients who underwent glenohumeral instability procedures from 2009 to 2018. Procedures were identified using Current Procedural Terminology codes for open Bankart, Latarjet, anterior bone block, posterior bone block, multidirectional capsular shift, and arthroscopic Bankart procedures. Sample weights provided by the database were used to calculate national estimates. US Census Bureau annual population data were used to calculate incidence. Future projections to 2030 were modeled using Poisson and linear regression. RESULTS: There were an estimated 446,072 glenohumeral instability cases from 2009 to 2018. The per capita incidence (per 100,000) remained constant, from 14.8 in 2009 to 14.5 in 2018. Arthroscopic Bankart procedures comprised the highest number of procedures throughout the study period, accounting for 89% of all procedures in 2009 and 93% in 2018. The number of open Bankart procedures decreased by 65% from 2009 to 2018, whereas the number of Latarjet procedures showed a 250% increase over the same period. Patient demographics did not change over the study period, and male patients aged 18-25 years comprised the largest demographic group undergoing anterior instability procedures. Multidirectional instability procedures exhibited the least pronounced sex differences. Future modeling from 2018 to 2030 projected a continued steady rise in arthroscopic Bankart procedures (from 40,000 to 49,000 cases/yr), rapid growth in Latarjet procedures (from 1370 to 4300 cases/yr), and continued decline in open Bankart procedures (from 1000 to 250 cases/yr). CONCLUSIONS: Arthroscopic Bankart repair continues to be the most common glenohumeral instability procedure in the United States. From 2009 to 2018, the incidence of open Bankart procedures declined whereas the incidence of Latarjet procedures markedly increased. Future projections to 2030 mirrored these findings. These data may provide an enhanced understanding of the evolution of surgical treatment of glenohumeral instability within the United States, laying the foundation for continued prospective studies into the appropriate indications and advancements in surgical techniques.

Long-Term Safety, Clinical and Immunological Outcomes in Primary Membranous Nephropathy with Severe Renal Impairment Treated with Cyclophosphamide and Steroid-Based Regimen.

Introduction and Aims: Therapy of primary membranous nephropathy (PMN) with progressive advanced kidney dysfunction is challenging with limited literature and no clear therapeutic strategies. This is due to the scant evidence of effectiveness and uncertainty around the risk-benefit profile of immunosuppression (ImS) when eGFR is less than 30 mL/min. We aimed to determine long-term clinical outcomes in patients with PMN and severe renal impairment treated with combined cyclophosphamide and steroids. Methods: The study is a single-center retrospective longitudinal cohort study. All patients (between 2004 and 2019) with biopsy confirmed PMN who initiated combination therapy with steroids and cyclophosphamide and had an eGFR of ≤30 mL/min/1.73 m2 at the time of initiation of therapy were included for analysis. Clinical and laboratory parameters including anti-PLA2R-Ab were monitored as per standard clinical guidance. Primary outcome was achievement of partial remission. Secondary outcomes included immunological remission, need for renal replacement therapy, and adverse effects. Results: Eighteen patients with median age of 68 (IQR 58-73) years and 5:1 M:F ratio received the combination therapy when eGFR was ≤30 mL/min/1.73 m2 (CKD-EPI). At time of ImS, median eGFR and uPCR were 23 (IQR 18-27) mL/min/1.73 m2 and 8.4 (IQR 6.9-10.7) g/g, respectively. Median follow-up was for 67 (IQR 27-80) months. 16 patients (89%) achieved partial remission and 7 (39%) achieved complete remission. eGFR increased by 7 mL/min/1.73 m2 (27%) after 1 year of starting ImS treatment and 12 mL/min/1.73 m2 at end of follow-up. Two patients (11%) developed end-stage renal disease needing renal replacement therapy. 67% achieved both immunological and clinical remission. At the end of the follow-up period, 2 (11%) patients required hospitalization secondary to infections, 4 (22%) patients developed cancer and 4 patients died (22%). Conclusion: Combination therapy with cyclophosphamide and steroids is effective in achieving partial remission and improving renal function in PMN with advanced renal dysfunction. Prospective controlled studies are required to provide further evidence to rationalize treatment and improve outcomes in such patients.

Intramedullary Metacarpal Fracture Fixation: A Biomechanical Study of Screw Diameter and Comparison With Intramedullary Wire Stabilization.

PURPOSE: Interest in intramedullary metacarpal fracture fixation (IMFF) with screws is increasing. However, the optimal screw diameter for fracture fixation is not yet established. In theory, larger screws should be more stable, but there is concern about long-term sequelae of larger metacarpal head defects and extensor mechanism injury created during insertion as well as implant cost. Therefore, the purpose of this study was to compare different diameter screws for IMFF to a popular and more cost-effective alternative of intramedullary wiring. METHODS: Thirty-two cadaveric metacarpals were used in a transverse metacarpal shaft fracture model. Treatment groups consisted of IMFF with 3.0 × 60 mm, 3.5 x 60 mm, and 4.5 x 60 mm screws as well as 4 1.1-mm intramedullary wires. Cyclic cantilever bending was performed with the metacarpals mounted at 45° to simulate physiologic loading. Cyclical loading at 10, 20, and 30 N was performed to determine fracture displacement, stiffness, and ultimate force. RESULTS: At 10, 20, and 30 N of cyclical loading, all screw diameters tested provided similar stability as measured by fracture displacement and were superior to the wire group. However, ultimate force under load to failure testing was similar between the 3.5- and 4.5-mm screws and superior to 3.0-mm screws and wires. CONCLUSIONS: For IMFF, 3.0, 3.5, and 4.5-mm diameter screws provide adequate stability for early active motion and are superior to wires. When comparing the different screw diameters, 3.5- and 4.5-mm diameter screws offer similar construct stability and strength superior to the 3.0-mm diameter screw. Therefore, to minimize metacarpal head morbidity, smaller screw diameters may be preferable. CLINICAL RELEVANCE: This study suggests that IMFF with screws is biomechanically superior to wires in cantilever bending strength in the transverse fracture model. However, smaller screws may be sufficient to permit early active motion while minimizing metacarpal head morbidity.

Variation in scapulohumeral rhythm on dynamic radiography in pathologic shoulders: a novel diagnostic tool.

HYPOTHESIS: The purpose of this study was to analyze the SHR of patients diagnosed with small (SRCTs) and massive rotator cuff tears (MRCTs), adhesive capsulitis (AC), and glenohumeral osteoarthritis (GH-OA) and compare their measurements to those of patient controls with healthy shoulders using DDR. We hypothesize that various diagnoses will vary with regards to SHR. METHODS: The sequences of pulsed radiographs collated in DDR to create a moving image were prospectively analyzed during humeral abduction in normal controls and in 4 distinct shoulder pathology groups: SRCT, MRCT, AC, and GH-OA. GH and ST joint angles were measured at 0°-30°, 30°-60°, 60°-90°, and maximal coronal plane humeral abduction. SHR was defined as the ratio of the change in humeral abduction over the change in scapula upward rotation during humeral abduction and was calculated within the above angle intervals. RESULTS: A total of 121 shoulders were analyzed. Forty normal controls were compared to 13 SRCTs, 29 MRCTs, 16 AC, and 23 GH-OA. SHR during humeral abduction differed significantly in patients with MRCT (1.91 ± 0.72), AC (1.55 ± 0.37), and GH-OA (2.31 ± 1.01) compared to controls (3.39 ± 0.79). When analyzed across 30° intervals of abduction, there was a significantly lower SHR found at 0°-30°, 30°-60°, and 60°-90° in MRCT, AC, and GH-OA across each motion range compared to controls. Control patients had an arc of abduction of 103° ± 32°, which was significantly larger than all other pathologies (MRCT: 76° ± 23°, SRCT: 81° ± 21°, AC: 65° ± 27°, GH-OA: 71° ± 35°) and an average scapular abduction of 33° ± 14°, which was significantly less than patients with an MRCT (46° ± 10°) and AC (65° ± 27°). CONCLUSION: SHR remained significantly lower throughout shoulder abduction in MRCT (43.65%), AC (-54.29%), and GH-OA (32.01%) compared to controls. When isolating for humeral and scapular motion, all 4 pathologies had decreased GH abduction, whereas AC and MRCT had an increased scapular compensatory motion compared to controls. Quantifying kinematic patterns like SHR using DDR can be implemented as a novel, safe, and cost-effective method to diagnose shoulder pathology and to monitor response to treatment.

Novel Diagnostic and Treatment Techniques for Neurogenic Thoracic Outlet Syndrome.

Neurogenic thoracic outlet syndrome is a challenging condition to diagnose and treat, often precipitated by the triad of repetitive overhead activity, pectoralis minor contracture, and scapular dyskinesia. The resultant protracted scapular posture creates gradual repetitive traction injury of the suprascapular nerve via tethering at the suprascapular notch and decreases the volume of the brachial plexus cords and axillary vessels in the retropectoralis minor space. A stepwise and exhaustive diagnostic protocol is essential to exclude alternate pathologies and confirm the diagnosis of this dynamic pathologic process. Ultrasound-guided injections of local anesthetic or botulinum toxin are a key factor in confirming the diagnosis and prognosticating potential response from surgical release. In patients who fail over 6 months of supervised physical therapy aimed at correcting scapular posture and stretching of the pectoralis minor, arthroscopic surgical release is indicated. We present our diagnostic algorithm and technique for arthroscopic suprascapular neurolysis, pectoralis minor release, brachial plexus neurolysis, and infraclavicular thoracic outlet decompression.

Machine Learning Can Predict Level of Improvement in Shoulder Arthroplasty.

The ability to accurately predict postoperative outcomes is of considerable interest in the field of orthopaedic surgery. Machine learning has been used as a form of predictive modeling in multiple health-care settings. The purpose of the current study was to determine whether machine learning algorithms using preoperative data can predict improvement in American Shoulder and Elbow Surgeons (ASES) scores for patients with glenohumeral osteoarthritis (OA) at a minimum of 2 years after shoulder arthroplasty. METHODS: This was a retrospective cohort study that included 472 patients (472 shoulders) diagnosed with primary glenohumeral OA (mean age, 68 years; 56% male) treated with shoulder arthroplasty (431 anatomic total shoulder arthroplasty and 41 reverse total shoulder arthroplasty). Preoperative computed tomography (CT) scans were used to classify patients on the basis of glenoid and rotator cuff morphology. Preoperative and final postoperative ASES scores were used to assess the level of improvement. Patients were separated into 3 improvement ranges of approximately equal size. Machine learning methods that related patterns of these variables to outcome ranges were employed. Three modeling approaches were compared: a model with the use of all baseline variables (Model 1), a model omitting morphological variables (Model 2), and a model omitting ASES variables (Model 3). RESULTS: Improvement ranges of ≤28 points (class A), 29 to 55 points (class B), and >55 points (class C) were established. Using all follow-up time intervals, Model 1 gave the most accurate predictions, with probability values of 0.94, 0.95, and 0.94 for classes A, B, and C, respectively. This was followed by Model 2 (0.93, 0.80, and 0.73) and Model 3 (0.77, 0.72, and 0.71). CONCLUSIONS: Machine learning can accurately predict the level of improvement after shoulder arthroplasty for glenohumeral OA. This may allow physicians to improve patient satisfaction by better managing expectations. These predictions were most accurate when latent variables were combined with morphological variables, suggesting that both patients' perceptions and structural pathology are critical to optimizing outcomes in shoulder arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Patient Perception of Pain Control (Not Opiate Amount) Affects Hospital Consumer Assessment of Healthcare Providers and Systems and Press Ganey Satisfaction Scores After Orthopaedic Trauma.

INTRODUCTION: Opiate abuse is a public health issue linked to prescribing. Prescribing increased partly in response to adopting pain as the fifth vital sign. Assessing pain control on patient satisfaction surveys, including government-mandated Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and optional private surveys (Press Ganey) administered on hospital discharge, may contribute. This study evaluates whether opiate amounts affect orthopaedic trauma patient perception of pain control and overall hospital rating on HCAHPS and Press Ganey surveys. METHODS: Consecutive adult patients >18 years surgically treated for isolated fractures (UE = upper extremity, LE = lower extremity, and PA = pelvis/acetabulum) at a level 1 trauma center between January 1, 2014, and December 31, 2016, were retrospectively analyzed. Hospital charts, HCAHPS, and Press Ganey data were reviewed; patients without survey responses were excluded. Data included comorbidities, psychiatric history, substance use, injury type, and surgery. Analysis included Spearman's rho for correlations, Wilcoxon rank-sum and Kruskal-Wallis for continuous variables, and adjusted ordinal regression to estimate association between opioid prescribing and patient ratings. RESULTS: One hundred fifty-two total patients (UE 29, LE 112, and PA 11) with mean age of 57 years and median length of stay 3 days were included. Adjusted models showed longer duration outpatient prescriptions were associated with lower rating on how often inpatient pain was controlled (P = 0.002), lower total MME inpatient was associated with higher ratings (HCAHPS P = 0.015; Press Ganey, P = 0.03), lower average daily MME inpatient was associated with lower ratings (HCAHPS P = 0.008; Press Ganey, P = 0.037), and shorter outpatient prescription duration was associated with lower ratings (P = 0.008). Patient perception of pain control was strongly associated with overall HCAHPS (P < 0.05) and Press Ganey (P < 0.001) ratings. DISCUSSION: Inpatient and outpatient opiate amounts and duration demonstrated some associations with overall scores. However, patients' pain control perception seems to have the strongest relationship with hospital rating. Counseling and multimodal pain control may lead to strong satisfaction scores without needing high opiates after orthopaedic trauma.

Indicators of metabolic syndrome in normotensive normoglycemic asthmatic patients.

BACKGROUND: Pathophysiology of hypertension and bronchial asthma (BA) shares many similarities, especially those related to the metabolic syndrome (MS). AIM: In this study, the indicators of the MS were evaluated in normoglycemic normotensive asthmatic patients to clarify if the components of the MS can still interact to increase the risk of BA, provided that blood pressure and glucose level are kept within the normal physiological ranges. METHODS: Body mass index (BMI), waist circumference (WC), mean arterial blood pressure (MABP), fasting blood glucose (FBG) and fasting blood insulin (FBI) levels, the quantitative insulin sensitivity check index (QUICKI), serum lipid profile, and spirometric measurements were all compared between 120 asthmatic patients and 59 non-asthmatic subjects. Cigarette smoking, pregnancy, age below 20 years or above 40 years, diabetes mellitus and hypertension, and other chronic diseases were excluded from all studied groups. RESULTS: Asthmatic patients demonstrated higher WC (median [25th-75th interquartile]=88.50 [78.00-101.75], FBI [19.98 (11.12-40.14)], and triglyceride (TG) level [109.5 (76.50-134.0)]) compared with non-asthmatic subjects (81.00 [72.00-92.00], 13.78 [8.84-30.24], and 89.00 [64.25-104], P<0.05). QUICKI and MABP were lower in asthmatic patients (0.310 [0.283-0.338] and 86.66 [83.33-93.33]) compared with non-asthmatic subjects (0.320 [0.297-0.353] and 93.33 [83.33-93.33]), (P<0.05). BMI, FBG, low-density lipoprotein, high-density lipoprotein, and total cholesterol levels were comparable in the studied groups. CONCLUSIONS: The present finding gives further evidence for higher WC, FBI, TG level, and insulin resistance in normotensive, normoglycemic asthmatic patients compared to healthy controls. RELEVANCE FOR PATIENTS: The findings of this study suggested that abdominal obesity, hypertriglyceridemia, hyperinsulinemia, and insulin resistance may still be interacting and hence increase the risk of BA in normotensive, normoglycemic subjects.

Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs.

Inhibitors of CDK4 and CDK6 have emerged as important FDA-approved treatment options for breast cancer patients. The properties and pharmacology of CDK4/6 inhibitor medicines have been extensively profiled, and investigations into the degradation of these targets via a PROTAC strategy have also been reported. PROTACs are a novel class of small-molecules that offer the potential for differentiated pharmacology compared to traditional inhibitors by redirecting the cellular ubiquitin-proteasome system to degrade target proteins of interest. We report here the preparation of palbociclib-based PROTACs that incorporate binders for three different E3 ligases, including a novel IAP-binder, which effectively degrade CDK4 and CDK6 in cells. In addition, we show that the palbociclib-based PROTACs in this study that recruit different E3 ligases all exhibit preferential CDK6 vs. CDK4 degradation selectivity despite employing a selection of linkers between the target binder and the E3 ligase binder.

Ultrasound diagnosis and therapeutic intervention in the spine.

Spine pathology afflicts people across the globe and is responsible for a large portion of physician visits and healthcare costs. Imaging such as plain radiographs, CT, MRI, and ultrasound is vital to assess structure, function, and stability of the spine and also provide guidance in therapeutic interventions. Ultrasound utilization in spine conditions is less ubiquitous, but provides benefits in low costs, portability, and dynamic imaging. This study assesses ultrasound efficacy in diagnosis and therapeutic interventions for spine pathology. A systematic review conducted via PubMed, MEDLINE, and Google Scholar identified 3,630 papers with eventual inclusion of 73 papers with an additional 21 papers supplemental papers subsequently added. Findings highlighted ultrasound utilization for different structural elements of the spine such as muscle, bone, disc, ligament, canal, and joints are presented and compared with radiographs, CT, and MRI imaging where relevant. Spinal curvature and mobility are similarly presented. Ultrasound efficacy for guided therapeutics about the spine is presented and assessed against other modalities. Ultrasound is a widely used and efficacious modality to guide injections about the spine. Diagnostic utility is less well studied, but shows promise in assessing fractures, posterior ligamentous stability, and intra-operative hardware placement. The low cost, portability, and dynamic imaging ability make it an attractive modality particularly for developing health systems and resource limited environments such as combat settings and the International Space Station. Further study is recommended before broad adoption in diagnostics.

Effects of spaceflight on cartilage: implications on spinal physiology.

Spaceflight alters normal physiology of cells and tissues observed on Earth. The effects of spaceflight on the musculoskeletal system have been thoroughly studied, however, the effects on cartilage have not. This area is gaining more relevance as long duration missions, such as Mars, are planned. The impact on intervertebral discs and articular cartilage are of particular interest to astronauts and their physicians. This review surveys the literature and reports on the current body of knowledge regarding the effects of spaceflight on cartilage, and specifically changes to the spine and intervertebral disc integrity and physiology. A systematic literature review was conducted using PubMed, MEDLINE, and Google Scholar. Eighty-six unique papers were identified, 15 of which were included. The effect of spaceflight on cartilage is comprehensively presented due to limited research on the effect of microgravity on the spine/intervertebral discs. Cellular, animal, and human studies are discussed, focusing on human physiologic changes, cartilage histology, mineralization, biomechanics, chondrogenesis, and tissue engineering. Several common themes were found, such as decreased structural integrity of intervertebral disks and impaired osteogenesis/ossification. However, studies also presented conflicting results, rendering strong conclusions difficult. The paucity of human cartilage studies in spaceflight leaves extrapolation from other model systems the only current option for drawing conclusions despite known and unknown limitations in applicability to human physiology, especially spinal pathophysiology which is special interest. The aerospace and biomedical research communities would benefit from further human spaceflight articular cartilage and intervertebral disc studies. Further research may yield beneficial application for spaceflight, and crossover in understanding and treating terrestrial diseases like osteoarthritis and vertebral disc degeneration.

The Incremental Burden of Acute Respiratory Distress Syndrome: Long-term Follow-up of a Population-Based Nested Case-Control Study.

OBJECTIVE: To evaluate the long-term survival of patients at similar risk for hospital-acquired acute respiratory distress syndrome (ARDS) who did and did not develop ARDS. METHODS: We conducted long-term follow-up of a population-based nested case-control study in a consecutive cohort of adult Olmsted County, Minnesota, patients admitted from January 1, 2001, through December 31, 2010. Patients in whom ARDS developed during their hospital stay (cases) were matched to similar-risk patients without ARDS (controls) by 6 characteristics: age, sex, sepsis, high-risk surgery, ratio of oxygen saturation to fraction of inspired oxygen, and ARDS risk according to the Lung Injury Prediction Score. Hospital mortality, discharge disposition, and long-term survival were compared. RESULTS: Patients who developed hospital-acquired ARDS (n=400) had higher hospital mortality than at-risk controls (n=400) (35% vs 5%; P<.001). Among hospital survivors (252 matched pairs), ARDS cases were more likely to be discharged to rehabilitation (13% vs 4%) and long-term care (30% vs 15%) facilities, whereas more controls were discharged home (71% vs 41%). After discharge, differences in survival persisted beyond 90 days (adjusted hazard ratio [HR], 1.76; 95% CI, 1.2-2.5; P=.002) and 6 months (adjusted HR, 1.73; 95% CI, 1.2-2.6; P<.001). CONCLUSION: These results suggest that in a population-based matched case-control study of patients with similar characteristics at the time of hospital admission, those who developed hospital-acquired ARDS had worse long-term survival.

Adverse in-hospital events are associated with increased in-hospital mortality and length of stay in patients with or at risk of acute respiratory distress syndrome.

OBJECTIVE: To explore the effect of various adverse hospital events on short- and long-term outcomes in a cohort of acutely ill hospitalized patients. PATIENTS AND METHODS: In a secondary analysis of a retrospective cohort of acutely ill hospitalized patients with sepsis, shock, or pneumonia or undergoing high-risk surgery who were at risk for or had developed acute respiratory distress syndrome between 2001 and 2010, the effects of potentially preventable hospital exposures and adverse events (AEs) on in-hospital and intensive care unit (ICU) mortality, length of stay, and long-term survival were analyzed. Adverse effects chosen for inclusion were inadequate empiric antimicrobial coverage, hospital-acquired aspiration, medical or surgical misadventure, inappropriate blood product transfusion, and injurious tidal volume while on mechanical ventilation. RESULTS: In 828 patients analyzed, the distribution of 0, 1, 2, and 3 or more cumulative AEs was 521 (63%), 126 (15%), 135 (16%), and 46 (6%) patients, respectively. The adjusted odds ratios (95% CI) for in-hospital mortality in patients who had 1, 2, and 3 or more AEs were 0.9 (0.5-1.7), 0.9 (0.5-1.6), and 1.4 (0.6-3.3), respectively. One AE increased the length of stay, difference between means (95% CI), in the hospital by 8.7 (3.8-13.7) days and in the ICU by 2.4 (0.6-4.2) days. CONCLUSION: Potentially preventable hospital exposure to AEs is associated with prolonged ICU and hospital lengths of stay. Implementation of effective patient safety interventions is of utmost priority in acute care hospitals.

Outcome of adverse events and medical errors in the intensive care unit: a systematic review and meta-analysis.

Adverse events and medical errors (AEs/MEs) are more likely to occur in the intensive care unit (ICU). Information about the incidence and outcomes of such events is conflicting. A systematic review and meta-analysis were conducted to examine the effects of MEs/AEs on mortality and hospital and ICU lengths of stay among ICU patients. Potentially eligible studies were identified from 4 major databases. Of 902 studies screened, 12 met the inclusion criteria, 10 of which are included in the quantitative analysis. Patients with 1 or more MEs/AEs (vs no MEs/AEs) had a nonsignificant increase in mortality (odds ratio = 1.5; 95% confidence interval [CI] = 0.98-2.14) but significantly longer hospital and ICU stays; the mean difference (95% CI) was 8.9 (3.3-14.7) days for hospital stay and 6.8 (0.2-13.4) days for ICU. The ICU environment is associated with a substantial incidence of MEs/AEs, and patients with MEs/AEs have worse outcomes than those with no MEs/AEs.

Off-hour admission and outcomes for patients with acute myocardial infarction undergoing percutaneous coronary interventions.

BACKGROUND: Prior studies have suggested that patients with acute myocardial infarction (AMI) who are admitted during off-hours (weekends, nights and holidays) have higher mortality when compared with patients admitted during regular hours. METHODS: We analyzed consecutive patients with AMI (ST-elevation myocardial infarction [STEMI] and non-STEMI) who were treated with percutaneous coronary interventions from January 1998 to June 2010 at an academic medical center. Multivariable logistic regression models were used to estimate the association between off-hour admission and clinical outcomes adjusted for demographic and clinical variables. RESULTS: There were 3,422 and 2,664 patients with AMI admitted during off-hours and regular hours, respectively. Patients admitted during off-hours were more likely to have STEMI (56% vs 48%, P < .001), have cardiogenic shock at presentation (6% vs 4%, P = .002), and develop shock after presentation (6% vs 5%, P = .004). After multivariable analyses, off-hour admission was not significantly associated with in-hospital mortality (odds ratio [OR] 1.12, 95% CI 0.84-1.49), 30-day mortality (OR 1.12, 0.87-1.45), or 30-day readmissions (OR 1.01, 0.84-1.20) but was significantly associated with composite major complications and any of emergent coronary artery bypass graft surgery, ventricular arrhythmia, stroke/transient ischemic attack, and gastrointestinal/retroperitoneal/intracranial bleeding (OR 1.27, 1.05-1.55, P = .015). There was no significant time trend in the adjusted mortality difference between off-hours and regular hours. The results were not different between STEMI and non-STEMI. CONCLUSIONS: Patients who were admitted during off-hours did not have higher mortality or readmission rates as compared with ones admitted during regular hours at an academic medical center.