Augmented Ulnar Collateral Ligament Repair With Structural Bioinductive Scaffold: A Biomechanical Study.

BACKGROUND: Elbow ulnar collateral ligament (UCL) repair with suture brace augmentation shows good time-zero biomechanical strength and a more rapid return to play compared with UCL reconstruction. However, there are concerns about overconstraint or stress shielding with nonabsorbable suture tape. Recently, a collagen-based bioinductive absorbable structural scaffold has been approved by the Food and Drug Administration for augmentation of soft tissue repair. PURPOSE/HYPOTHESIS: This study aimed to assess the initial biomechanical performance of UCL repair augmented with this scaffold. We hypothesized that adding the bioinductive absorbable structural scaffold to primary UCL repair would impart additional time-zero restraint to the valgus opening. STUDY DESIGN: Controlled laboratory study. METHODS: Eight cadaveric elbow specimens-from midforearm to midhumerus-were utilized. In the native state, elbows underwent valgus stress testing at 30o, 60o, and 90o of flexion, with a cyclical valgus rotational torque. Changes in valgus rotation from 2- to 5-N·m torque were recorded as valgus gapping. Testing was then performed in 4 states: (1) native intact UCL-with dissection through skin, fascia, and muscle down to an intact UCL complex; (2) UCL-transected-distal transection of the ligament off the sublime tubercle; (3) augmented repair with bioinductive absorbable scaffold; and (4) repair alone without scaffold. The order of testing of repair states was alternated to account for possible plastic deformation during testing. RESULTS: The UCL-transected state showed the greatest increase in valgus gapping of all states at all flexion angles. Repair alone showed similar valgus gapping to that of the UCL-transected state at 30° (P = .62) and 60° of flexion (P = .11). Bioinductive absorbable scaffold-augmented repair showed less valgus gapping compared with repair alone at all flexion angles (P = .021, P = .024, and P = .024 at 30°, 60°, and 90°, respectively). Scaffold-augmented repair showed greater gapping compared with the native state at 30° (P = .021) and 90° (P = .039) but not at 60° of flexion (P = .059). There was no difference when testing augmented repair or repair alone first. CONCLUSION: UCL repair augmented with a bioinductive, biocomposite absorbable structural scaffold imparts additional biomechanical strength to UCL repair alone, without overconstraint beyond the native state. Further comparative studies are warranted. CLINICAL RELEVANCE: As augmented primary UCL repair becomes more commonly performed, use of an absorbable bioinductive scaffold may allow for improved time-zero mechanical strength, and thus more rapid rehabilitation, while avoiding long-term overconstraint or stress shielding.

Evaluating ChatGPT's Accuracy in Providing Screening Mammography Recommendations among Older Women: Artificial Intelligence and Cancer Communication.

Abstract Objective: The U.S. Preventive Services Task Force (USPSTF) recommends biennial screening mammography through age 74. Guidelines vary as to whether or not they recommended mammography screening to women aged 75 and older. This study aims to determine the ability of ChatGPT to provide appropriate recommendations for breast cancer screening in patients aged 75 years and older. Methods: 12 questions and 4 clinical vignettes addressing fundamental concepts about breast cancer screening and prevention in patients aged 75 years and older were created and asked to ChatGPT three consecutive times to generate 3 sets of responses. The responses were graded by a multi-disciplinary panel of experts in the intersection of breast cancer screening and aging . The responses were graded as 'appropriate', 'inappropriate', or 'unreliable' based on the reviewer's clinical judgment, content of the response, and whether the content was consistent across the three responses . Appropriateness was determined through a majority consensus. Results: The responses generated by ChatGPT were appropriate for 11/17 questions (64%). Three questions were graded as inappropriate (18%) and 2 questions were graded as unreliable (12%). A consensus was not reached on one question (6%) and was graded as no consensus. Conclusions: While recognizing the limitations of ChatGPT, it has potential to provide accurate health care information and could be utilized by healthcare professionals to assist in providing recommendations for breast cancer screening in patients age 75 years and older. Physician oversight will be necessary, due to the possibility of ChatGPT to provide inappropriate and unreliable responses, and the importance of accuracy in medicine.

Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials.

Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings.

Association of Quadriceps Tendon Harvest for ACL Reconstruction With Development of Osteochondritis Dissecans of the Patella in Pediatric Patients.

Background: There are various reported complications after primary anterior cruciate ligament reconstruction (ACLR) necessitating additional surgery in skeletally immature patients, regardless of technique and autograft type. Purpose: To analyze the rate and type of complications encountered with soft tissue quadriceps tendon autograft (QTA) for ACLR in patients ≤18 years as well as the overall rate of second surgery, unrelated to the use of the QTA. Study Design: Case series; Level of evidence, 4. Methods: A total of 141 patients ≤18 years who underwent ACLR with a QTA and had minimum 6-month follow-up were included. All patients underwent ACLR by utilizing a full-thickness soft tissue QTA. Complications associated with the QTA harvest site and use of QTA were reported. Results: The mean age of the included cohort (84 men, 57 women) was 14.8 ± 1.6 years. The average follow-up was of 2.0 ± 1.2 years. A total of 30 (21%) patients had a subsequent complication that required surgical intervention; in 11 (8%) patients, the complication was specifically associated with the use of a QTA, whereas in 19 (13%) patients, the complication was related to the ACLR. In addition, 13 (9%) patients underwent a contralateral ACLR procedure. Of the QTA-related complications, 2 patients developed osteochondritis dissecans (OCD)-like lesions in the superior aspect of the patella, 2 patients had injured their quadriceps extensor mechanism and required surgical repair, and 8 patients had a subsequent procedure to remove nonabsorbable sutures used for donor site quadriceps tendon closure. One of the patients who underwent the removal of nonabsorbable sutures also had an arthroscopic debridement of patellar chondral damage. Conclusion: We reported complications encountered with soft tissue QTA for ACLR. The complication rate for QTA harvest was 8%. However, given that the removal of nonabsorbable sutures from the donor site was caused by the surgical technique used, the revised nonsuture-related complication rate for QTA graft harvest was 2%. Although the use of a QTA has recently gained popularity due to its high return-to-sport and low graft-failure rates, surgeons should be aware of the complications associated with using this graft type.

Use of artificial intelligence in the management of T1 colorectal cancer: a new tool in the arsenal or is deep learning out of its depth?

The field of artificial intelligence is rapidly evolving, and there has been an interest in its use to predict the risk of lymph node metastasis in T1 colorectal cancer. Accurately predicting lymph node invasion may result in fewer patients undergoing unnecessary surgeries; conversely, inadequate assessments will result in suboptimal oncological outcomes. This narrative review aims to summarize the current literature on deep learning for predicting the probability of lymph node metastasis in T1 colorectal cancer, highlighting areas of potential application and barriers that may limit its generalizability and clinical utility.

Clinician and patient perspectives on screening mammography among women age 75 and older: A pilot study of a novel decision aid.

Objective: Supporting patient-clinician communication is key to implementing tailored, risk-based screening for older adults. Objectives of this multiphase mixed methods study were to identify factors that primary care clinicians consider influential when making screening mammography recommendations for women ≥ 75 years, develop a patient decision aid that incorporates these factors, and gather feasibility and acceptability from the patients' perspective. Methods: Clinicians from a Mid-Atlantic practice network completed online surveys. Women in the same network completed surveys before and after receiving a tailored booklet that included information about the benefits and harms of screening for women ≥ 75 years, a breast cancer risk-estimate, and a question prompt list to support patient-clinician communication. Results: Clinicians (N = 21) were primarily women [57.1%] and practiced family medicine [81.0%]. They cited patients' age ≥ 75 years [95.4%], comorbidity [86.4%], functional status [77.3%], cancer family history [63.6%], U.S. Preventive Services Task Force guidelines [81.8%] and new research [77.3%] as factors influencing their recommendations. Fourteen women completed baseline surveys and received personalized decision aids (Mean age = 79.1 years). Eleven completed the post-intervention survey. All were satisfied with the booklet length, 81.8% found the booklet easy to understand and 72.7% helpful in decision-making Perceived lifetime breast cancer risk decreased significantly from pre- to post-intervention (p = 0.02). Conclusions: Results suggest this decision aid, which incorporates key decisional factors from the clinician's perspective, is feasible and acceptable to patients. Innovation: A tailored decision aid booklet is innovative as it provides information on personalized risk and potential benefits and harms to older women considering screening.

An Estimate of Severe Harms Due to Screening Colonoscopy: A Systematic Review.

OBJECTIVE: This study aims to comprehensively assess the direct, severe harms of screening colonoscopy in the United States. Whereas other investigators have completed systematic reviews estimating the harms of all types of colonoscopy, this analysis focuses on screening colonoscopies that had adequate follow up to avoid undercounting delayed harms. DATA SOURCES: PubMed and Embase were queried for relevant studies on screening colonoscopy harms published between January 1, 2002, and April 1, 2022. STUDY SELECTION: English-language studies of screening colonoscopy for average risk patients were included. Studies must have followed patients for adequate time post procedure, defined as 30 days after colonoscopy. MAIN OUTCOMES: The primary outcome was the number of severe bleeding events and gastrointestinal (GI) perforations within 30 days of screening colonoscopy. RESULTS: A total of 1951 studies were reviewed for inclusion; 94 were reviewed in full text. Of those reviewed in full, 6 studies, including a total of 467,139 colonoscopies, met our inclusion criteria and were included in our analysis of harms related to screening colonoscopies. The rate of severe bleeding ranged credibly from 16.4 to 36.18 per 10,000 colonoscopies; the rate of perforation ranged credibly from 7.62 to 8.50 per 10,000 colonoscopies. CONCLUSIONS: This study is the first to estimate direct harms from screening colonoscopy, including harms that occur up to 30 days after the procedure. The risk of harm subsequent to screening colonoscopy is higher than previously reported and should be discussed with patients when engaging in shared decision making.

Real-World Validation of a Computer-Aided Diagnosis System for Prediction of Polyp Histology in Colonoscopy: A Prospective Multicenter Study.

INTRODUCTION: Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting. METHODS: We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience. RESULTS: A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%. DISCUSSION: The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice.

The utility of non-invasive tests to assess advanced fibrosis in Asian subjects with chronic hepatitis B and concomitant hepatic steatosis.

BACKGROUND: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver-related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non-invasive tests (NITs) including FIB-4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. AIM: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. METHODOLOGY: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. RESULTS: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62-0.69) for FIB-4 and 0.63 (95% CI 0.60-0.66) for APRI. The specificities were 0.94 for FIB-4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63-0.71) for FIB-4, 0.60 (95% CI 0.56-0.64) for APRI and 0.65 (95% CI 0.61-0.69) for NFS. The specificities were 0.95 for FIB-4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. CONCLUSION: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB-4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects.

Achilles Tendon Repairs: Identification of Risk Factors for and Economic Impact of Complications and Reoperation.

BACKGROUND: Compared with nonoperative management, Achilles tendon repair is associated with increased rates of complications and increased initial healthcare cost. However, data are currently lacking on the risk factors for these complications and the added healthcare cost associated with common preoperative comorbidities. HYPOTHESIS: Identify the independent risk factors for complications and reoperation after acute Achilles tendon repair and calculate the added cost of care associated with having each preoperative risk factor. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A retrospective review of a large commercial claims database was performed to identify patients who underwent primary operative management for Achilles tendon rupture between 2007 and 2016. The primary outcome measures of the study were risk factors for (1) postoperative complications, (2) revision surgery, and (3) increased healthcare resource utilization. RESULTS: A total of 50,279 patients were included. The overall complication rate was 2.7%. The most common 30-day complication was venous thromboembolism (1.2%). The rate of revision surgery was 2.5% at 30 days and 4.3% at 2 years. Independent risk factors for 30-day complications in our cohort included increasing age, hyperlipidemia, hypertension, female sex, obesity, and diabetes. Independent risk factors for revision surgery within 2 years included female sex, tobacco use, hypertension, obesity, and the presence of any postoperative complication. The average 5-year cost of operative intervention was $17,307. The need for revision surgery had the largest effect on 5-year overall cost, increasing it by $6776.40. This was followed by the presence of a postoperative complication ($3780), female sex ($3207.70), and diabetes ($3105). CONCLUSION: Achilles tendon repair is a relatively low-risk operation. Factors associated with postoperative complications include increasing age, hyperlipidemia, hypertension, female sex, obesity, and diabetes. Factors associated with the need for revision surgery include female sex, hypertension, obesity, and the presence of any postoperative complication. Female sex, diabetes, the presence of any complication, and the need for revision surgery had the largest added costs associated with them. CLINICAL RELEVANCE: Surgeons can use this information for preoperative decision-making and during the informed consent process.

Orthobiologic Techniques for Surgical Augmentation.

General awareness and clinical utilization of orthobiologic therapy has increased sharply in the recent years. Orthobiologics can be defined as "biological materials and substrates that promote bone, ligament, muscle, and tendon healing." There are 3 major strategies by which orthobiologics are thought to augment tissue repair or native biologic potential: factor-based, cell-based, and biomechanical augmentation. The purpose of this review is to synthesize the recent literature on orthobiologic techniques for surgical augmentation, with focus on several key areas including meniscus repair, osteochondral grafting, and rotator cuff repair.

An Occult Cardiac Tamponade: Echocardiographic Diagnosis of Aortic Root Rupture in Infective Endocarditis.

Infective endocarditis (IE) remains a rare yet critically severe condition, representing a considerable diagnostic challenge, especially among patients with pre-existing structural heart anomalies. This report details the clinical journal of a 49-year-old male with a known bicuspid aortic valve who initially exhibited nonspecific symptoms, leading to rapid clinical deterioration and the emergence of uncommon complications. The patient experienced an aortic root rupture and pericardial tamponade, necessitating urgent surgical intervention. Transesophageal echocardiography (TEE) was instrumental in confirming the diagnosis and facilitating the decision to perform a Bentall's procedure. This care highlights the critical role of TEE in diagnosing complex cases of IE and the imperative for swift intervention.

Emergence of Interlayer Coherence in Twist-Controlled Graphene Double Layers.

We report enhanced interlayer tunneling with reduced linewidth at zero interlayer bias in a twist-controlled double monolayer graphene heterostructure in the quantum Hall regime, when the top (ν_{T}) and bottom (ν_{B}) layer filling factors are near ν_{T}=±1/2,±3/2 and ν_{B}=±1/2,±3/2, and the total filling factor ν=±1 or ±3. The zero-bias interlayer conductance peaks are stable against variations of layer filling factor, and signal the emergence of interlayer phase coherence. Our results highlight twist control as a key attribute in revealing interlayer coherence using tunneling.

Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication.

BACKGROUND: One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy. AIM: To verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort. METHODS: Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. RESULTS: Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. CONCLUSION: One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.