Intrathecal Drug Delivery System in Prepontine Cistern for Patients with Intractable Craniofacial Cancer Pain: A Multicenter Retrospective Study.

BACKGROUND: Patients with craniofacial cancer frequently suffer from severe pain. The traditional intrathecal, oral, or intravenous analgesics could only provide insufficient pain relief with many side effects. Thus, a more effective analgesia approach is required. This study aimed to investigate the safety and efficacy of placing the catheter of an intrathecal morphine pump in the prepontine cistern for the treatment of craniofacial cancer pain. METHODS: We performed a retrospective study of patients with primary or metastatic craniofacial cancer pain who received the catheter placement of an intrathecal morphine pump into the prepontine cistern in eleven medical centers from September 2019 to December 2023. Friedman test and pairwise signed-rank test were used to evaluate the difference in numeric rating scale (NRS) scores, the number of breakthrough pain episodes, dose of intrathecal morphine, and dose of systemic morphine equivalents (oral, patch, intravenous) from preoperative period to postoperative days 1, 7, and 30. P values were corrected for multiple comparisons using Bonferroni test. RESULTS: The study included 33 patients. The median (interquartile range [IQR]) of NRS scores at days 1, 7, and 30 postimplant were 2.0 (1.0-3.5), 2.0 (1.0-2.0), and 1.0 (1.0-2.0), respectively, which was significantly lower than that before surgery (median, 8.0; IQR, 7.0-10.0; all P < .001). Compared to baseline number/d of breakthrough pain episodes (median, 6.0; IQR, 4.5-10.0), there was a progressive decrease in the number/d of breakthrough pain episodes at day 1, day 7, and day 30 postimplant, and the median (IQR) were 1.0 (0.0-3.0), 2.0 (0.0-3.0), and 0.0 (0.0-1.2), respectively (all P < .001). Approximately 78.8% and 96.7% of patients reported pain relief >50% at days 1 and 30 postimplant, respectively. Compared with that at day 1 postimplant, the proportion of patients with a pain relief rate >75% at day 30 postimplant also increased with continued intrathecal treatment. Compared to the dose of baseline systemic morphine equivalents (median, 228 mg.d-1; IQR, 120-408 mg.d-1), the dose of systemic morphine equivalents reduced significantly from 0(0-120) mg.d-1 at day 1 postimplant (P = .001), to 0 (0-0) mg.d-1 at days 7 and 30 postimplant (both P < .001). Few patients reported perioperative adverse events, including nausea, constipation, hypotension, urinary retention, dry mouth, headache, and sedation. No severe adverse events occurred. CONCLUSIONS: Placing the catheter tip of an intrathecal morphine pump into the prepontine cistern could effectively relieve refractory craniofacial cancer pain with an extremely low total morphine dose requirement and few adverse events. This procedure could be considered in patients with severe refractory craniofacial cancer pain.

Randomized Controlled Trials Comparing Bone-Patellar Tendon-Bone Versus Hamstring Tendon Autografts in Anterior Cruciate Ligament Reconstruction Surgery Are Statistically Fragile: A Systematic Review.

PURPOSE: To assess the statistical fragility of recently published randomized controlled trials (RCTs) comparing the use of hamstring tendon autograft with bone-patellar tendon-bone autograft for anterior cruciate ligament (ACL) reconstruction. METHODS: The PubMed, Embase, and MEDLINE databases were queried for RCTs published since 2010 comparing autograft type (bone-patellar tendon-bone vs hamstring tendon) in ACL reconstruction surgery. The fragility index (FI) and reverse FI (rFI) were determined for significant and nonsignificant outcomes, respectively, as the number of outcome reversals required to change statistical significance. The fragility quotient (FQ) and reverse FQ, representing fragility as a proportion of the study population, were calculated by dividing the FI and rFI, respectively, by the sample size. RESULTS: We identified 19 RCTs reporting 55 total dichotomous outcomes. The median FI of the 55 total outcomes was 5 (interquartile range [IQR], 4-7), meaning a median of 5 outcome event reversals would alter the outcomes' significance. Five outcomes were reported as statistically significant with a median FI of 4 (IQR, 2-6), meaning a median of 4 outcome event reversals would change outcomes to be nonsignificant. Fifty outcomes were reported as nonsignificant with a median rFI of 5 (IQR, 4-7), meaning a median of 5 outcome event reversals would change outcomes to be significant. The FQ and reverse FQ for significant and nonsignificant outcomes were 0.025 (IQR, 0.018-0.045) and 0.082 (IQR, 0.041-0.106), respectively. For 61.8% of outcomes, patients lost to follow-up exceeded the corresponding FI or rFI. CONCLUSIONS: There is substantial statistical fragility in recent RCTs on autograft choice in ACL reconstruction surgery given that altering a few outcome events is sufficient to reverse study findings. For over half of outcomes, maintaining patients lost to follow-up may have been sufficient to reverse study conclusions. CLINICAL RELEVANCE: We recommend co-reporting FIs and P values to provide a more comprehensive representation of a study's conclusions when conducting an RCT.

Demographic and Academic Characteristics of Orthopaedic Shoulder and Elbow Division Chiefs in the United States.

INTRODUCTION: Division Chiefs (DCs) and department leadership play an integral role within the service, and in the department as a whole. The goal of this study was to assess the demographics and academic characteristics of the leadership in orthopedic shoulder and elbow services across academic centers in the United States and comment on the diversity within these leadership positions. METHODS: Academic medical centers were identified using the FRIEDA database. DCs were identified using the hospitals' respective websites where data such as sex, race/ethnicity, academic rank, fellowship institution, and time since graduating fellowship. Scopus database was used to determine individual h-indices. RESULTS: Of 198 academic programs identified, 49 were found to have a DC of the orthopedic shoulder and elbow division. An additional 26 programs were noted to have a shoulder and elbow division, but were not found to have a DC of the division. These DCs were mostly White (n=43, 87.8%), with only 6 identified DCs with a different ethnicity. Forty-five of the DCs (91.8%) were male and 4 were female (8.2%). The average time out of fellowship was 20.7 years and the average h-index was 18.9. More than 20% of the DCs trained at Columbia's Neer shoulder and elbow Fellowship. Six DCs were current or past president of ASES and 5 DCs completed the ASES traveling fellowship. CONCLUSIONS: There is a paucity of available research on demographic and leadership characteristics in academic orthopedic shoulder and elbow. Shoulder and elbow DC had average h-index of 18.9 and 20% trained at one fellowship. There also opportunities for increased gender/racial/ethnic diversity among the leadership of shoulder and elbow divisions.

Sex and Age-Specific Analysis of Basketball-Related Shoulder Dislocations in the United States: A National Injury Data Review.

HYPOTHESIS/PURPOSE: Basketball-related shoulder dislocations frequently present to emergency departments (EDs) in the US. This study aimed to identify the primary mechanisms, distributions, and trends of these injuries. METHODS: All data was extracted from the National Electronic Injury Surveillance System (NEISS), a public database representing approximately 100 US EDs. NEISS was queried for all basketball-related injuries and shoulder dislocations from January 1, 2013 to December 31, 2022. Clinical narratives were used to assign injury mechanisms and the presence of player contact. RESULTS: Between 2013 and 2022, 52,417 basketball-related shoulder dislocations were reported. 30.9% of all basketball-related shoulder injuries were dislocations, and 30.5% of all joint dislocations occurred at the shoulder. Basketball-related shoulder dislocations decreased significantly from 2013-2022 (p<.001). From 2019 to 2020, a 31.0% decrease was identified. The most common mechanism of shoulder dislocation was falling (36.9%). Males accounted for 92.5% of all shoulder dislocations. However, females were significantly more likely than males to dislocate their shoulders from player contact (15.5% of female dislocations v. 10.0% of male dislocations, p<.001). Only 0.2% of all dislocations resulted in hospitalization. 10.4% of dislocations resulted from contact with another player. Compared to other age groups, young adults (43.3%) and adolescents (42.7%) presented with the majority of shoulder dislocations. Children were more likely to dislocate their shoulder from sustaining a direct blow (25.5%), while all other age groups were more likely to have fallen. Children were also the most likely to sustain a dislocation involving player contact (23.9%). CONCLUSION: Basketball-related shoulder dislocations decreased significantly from 2013 to 2022. Females and children were significantly more likely to present with a dislocation by sustaining player contact. Across all demographics, teaching athletes how to break their falls safely may decrease rates of dislocation by minimizing impacts on a posteriorly outstretched arm.

Academic and Demographic Characteristics of Pediatric Orthopaedic Division Chiefs in the United States.

INTRODUCTION: Division Chiefs (DCs) and department leadership play an integral role within the service. The goal of this study is to assess the demographics and scholarly work of the leadership in pediatric orthopaedics services across the United States and comment on the role of diversity within leadership positions. METHODS: Academic medical centers and pediatric hospitals were identified using the Electronic Residency Application Service website, the Pediatric Orthopaedic Society of North America website, and the Children's Hospital Association website. Leadership was identified using the hospitals' respective websites where data such as sex, race/ethnicity, fellowship institution, time since graduating fellowship, and academic rank were collected. Scopus database was used to determine h-indices and PubMed was used to determine the number of publications. RESULTS: Of 196 academic centers and 223 pediatric hospitals identified, 98 had a designated DC of the pediatric orthopaedics division. The majority of the DCs were male (85.7%), and leadership positions at hospitals with academic affiliations had a higher proportion of female DCs than nonacademic centers ( P =0.0317). DCs were mostly white (83.7%), followed by Asian (12.2%), and African American (2.0%). The average time since fellowship was 21.1 years and the average h-index was 15.7. The average age of the DCs was 56.8 years old. Of those in academic settings, 48.5% held the rank of professor. The fellowship programs that trained the most DCs were Boston Children's Hospital (16.3%) and Texas Scottish Rite for Children (14.3%). DISCUSSION: There is a paucity of available research on leadership characteristics in pediatric orthopaedic surgery. While progress has been made, there is still a lack of diversity that exists among leadership in pediatric orthopaedics, both within the academic setting as well as the private sector. The position of DC is held predominately by white males with a rank of either professor or no academic association. Intentional efforts are needed to continue to increase diversity in leadership positions within pediatric orthopaedic programs in the United States. LEVEL OF EVIDENCE: IV.

The Lack of Reporting Social Determinants of Health in Pediatric Orthopaedic Randomized Controlled Trials.

BACKGROUND: Social determinants of health (SDOHs) affect health outcomes outside the hospital, and understanding them can enhance postoperative outcomes in orthopaedic surgery patients. This study aimed to describe the prevalence of randomized controlled trials (RCTs) in pediatric orthopaedic journals reporting on the SDOHs of their patient cohorts. We hypothesize that many SDOHs will be underreported in RCTs investigating pediatric orthopaedic surgery. METHODS: Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the authors queried the PubMed database to examine SDOHs from 2 pediatric orthopaedic journals: Journal of Pediatric Orthopaedics and Journal of Pediatric Orthopaedics: Part B. The inclusion criteria incorporated RCTs published between 2005 and April 2024. The exclusion criteria included any articles that were not RCTs published in this period. RESULTS: One hundred thirteen articles met the search criteria, with 31 excluded because they did not fall from 2005 to 2024. Eighty-two were published from 2005 to 2024, but 6 RCTs were excluded, as 3 were non-RCTs, and 3 examined cadavers. Seventy-six RCTs were included for analysis, with 65 articles from the Journal of Pediatric Orthopaedics and 11 articles from the Journal of Pediatric Orthopaedics: Part B. Articles originated from 17 countries, with the United States producing 61.8% (47) of the included studies. Of all 76 included studies, 96.1% (73) reported age, 88.2% (67) reported sex/gender, 30.3% (23) reported BMI, 21.1% (16) reported race/ethnicity, 5.3% (4) reported educational level, 2.6% (2) reported stress, and 2.6% (2) reported insurance. Smoking status, socioeconomic status, income levels, and employment status were each reported by only 1 study. CONCLUSIONS: The RCTs examining pediatric orthopaedic surgery tend to scarcely report SDOHs. Future RCTs should expand beyond demographic characteristics such as age, race/ethnicity, sex/gender, and BMI and incorporate other relevant SDOHs. This will allow us to develop a more comprehensive understanding of health outcomes in the pediatric orthopaedic population. LEVEL OF EVIDENCE: I; Therapeutic Studies.

MicroRNA-330-5p Mediates the TDRG1-Regulated Myocardial Inflammation and Apoptosis after Myocardial Infarction by Inhibiting MAPK1.

Acute myocardial infarction (AMI) is a cardiovascular illness with the highest disability and mortality rates worldwide. This study aimed to estimate the mechanism of TDRG1 in myocardial damage.qRT-PCR was used to study the levels of TDRG1. After establishing hypoxia/reoxygenation (H/R) model, the inflammation was assessed by qRT-PCR, oxidation was detected by commercial kits, and apoptosis was estimated by qRT-PCR and flow cytometry. The luciferase intensity and RNA immunoprecipitation assay were detected for the identification of target relationship. The functional enrichment was unveiled by GO and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein interaction was conducted for screening key genes.The expression of TDRG1 was elevated and negatively correlated with miR-330-5p in the serum AMI patients. TDRG1/miR-330-5p axis regulated inflammation, oxidation, and viability and apoptosis of HL-1 cells induced by H/R. GO and KEGG analyses indicate that 76 overlapping targets of miR-330-5p were primarily involved in focal adhesion, calmodulin binding, and ErbB and Rap1 signaling pathways. MAPK1 was the top key gene and was a target gene of miR-330-5p.TDRG1/miR-330-5p axis could participate in the regulation of apoptosis and inflammation of H/R-induced cardiomyocytes.

[Effect of Staphylococcal Nuclease and Tudor Domain Containing 1/SLC7A11 on the Occurrence and Development of Osteosarcoma by Inhibiting Ferroptosis].

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

Technical guideline for intra-prepontine cisternal drug delivery via spinal puncture through subarachnoid catheterization. / ç»è„ŠæŸ±æ¤Žé—´éš™ç©¿åˆºè››ç½‘è†œä¸‹è ”è„‘æ¡¥å‰æ± ç½®ç®¡è¯ç‰©è¾“æ³¨æŠ€æœ¯åº”ç”¨æŒ‡å—.

OBJECTIVES: The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain, such as trigemina neuralgia. This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. METHODS: A modified Delphi approach was used to work for this guideline. On the issues related to the intra-prepontine cisternal targeted drug delivery technique, the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. RESULTS: For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique, a consensus was formed on 7 topics (with an agreement rate of more than 80%), including the principles of the technique, indications and contraindications, patient preparation, surgical specifications for intra-prepontine cisternal catheter placement, analgesic dosage coordination, analgesic management, and prevention and treatment of complications. CONCLUSIONS: Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive, secure, and effective treatment. This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments, justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

AggBERT: Best in Class Prediction of Hexapeptide Amyloidogenesis with a Semi-Supervised ProtBERT Model.

The prediction of peptide amyloidogenesis is a challenging problem in the field of protein folding. Large language models, such as the ProtBERT model, have recently emerged as powerful tools in analyzing protein sequences for applications, such as predicting protein structure and function. In this article, we describe the use of a semisupervised and fine-tuned ProtBERT model to predict peptide amyloidogenesis from sequences alone. Our approach, which we call AggBERT, achieved state-of-the-art performance, demonstrating the potential for large language models to improve the accuracy and speed of amyloid fibril prediction over simple heuristics or structure-based approaches. This work highlights the transformative potential of machine learning and large language models in the fields of chemical biology and biomedicine.

Editorial Commentary: Glenoid Reconstruction With Autologous Tricortical Iliac Crest Represents an Alternative to Bankart Repair and Remplissage for Anterior Shoulder Instability With Subcritical Bone Loss.

Traumatic anterior shoulder dislocations are estimated to occur in approximately 2% of the population, frequently with concomitant anterior-inferior labral tears and associated Hill-Sachs lesions of the humeral head. So-called bipolar (or engaging) lesions with attritional bone loss may be exacerbated by recurrent instability, in terms of both prevalence and severity. The glenoid track concept and distance to dislocation have offered context for evaluating bipolar lesions, and increasingly, options for bone block reconstruction are considered for definitive treatment. Recently, concerns have been raised regarding coracoid transfer or Latarjet treatment, particularly with screw constructs in which catastrophic failure, hardware breakage, and secondary arthritis may develop. The Eden-Hybinette procedure, or tricortical iliac crest autograft bone augmentation, may represent a promising alternative to existing options while also restoring native glenoid bone stock. Additionally, suture button fixation may obviate the traditional pitfalls of prior bone block procedures while also achieving reproducible functional outcomes and low rates of recurrence. However, this must be considered alongside other contemporary arthroscopic treatments, such as combined arthroscopic Bankart repair and remplissage.

Arthroscopic repair of degenerative medial meniscus tears in patients aged over 45 years resulted in favorable clinical outcomes and low clinical failure rates at a minimum 2-year follow-up.

PURPOSE: This study aimed to investigate clinical and radiological results of arthroscopic repair for isolated medial degenerative meniscus tears (DMTs) in patients over 45 years old at a minimum 2-year follow-up. METHODS: From 2013 to 2017, patients aged over 45 years with isolated medial DMT refractory to conservative management or with true mechanical symptoms who had undergone arthroscopic repair were retrospectively reviewed. Arthroscopic meniscus repair was performed using all-inside or all-inside and inside-out technique in combination with bone marrow venting procedure. Tear patterns were classified according to arthroscopic findings. Magnetic resonance imaging (MRI) and outcome evaluations, including Lysholm score, Tegner activity score, and International Knee Documentation Committee (IKDC) score, were evaluated preoperatively and at the final follow-up. International Cartilage Repair Society grades of the medial compartments and MRI signal at tear sites were assessed preoperatively and at the final follow-up. A grade 0 to 2 signal at the repair site suggested a healed meniscus, whereas a grade 3 signal suggested an unhealed meniscus. Clinical failure was determined according to Barrett criteria. RESULTS: Twenty-seven patients (mean age, 57.7 ± 7.4 years) were enrolled. The mean follow-up was 52.0 ± 15.6 months. Among tear patterns, 48% were complex tears, 30% were horizontal tears, and 22% were other patterns. The mean Lysholm score and IKDC score significantly improved from 53 ± 25 to 89 ± 15 (p < 0.001) and 34 ± 24 to 72 ± 15 (p < 0.001) at the final follow-up, respectively. The median Tegner activity score significantly improved from 1 (range 1-4) to 4 (range 2-7, p < 0.001). Three (11%) patients were considered clinical failures, and five patients (19%) had cartilage lesion progression. At the final follow-up, MRI showed grade 0 in one (4%) patient, grade 1 in nine (33%) patients, grade 2 in six (22%) patients, and grade 3 in eleven (41%) patients. CONCLUSION: Arthroscopic repair of isolated medial DMT refractory to conservative management or with true mechanical symptoms in patients aged over 45 years had good to excellent clinical outcomes with low clinical failure rates, despite unhealed menisci being observed on MRI in 41% of patients at a mean 4.3-year follow-up. Arthroscopic repair could be a treatment option for these patients. LEVEL OF EVIDENCE: IV.

The fragility of statistical findings in distal biceps tendon repairs: a systematic review of randomized controlled trials.

BACKGROUND: The purpose of this present study was to perform a fragility analysis to assess the robustness of randomized controlled trials (RCTs) evaluating the distal biceps tendon repairs. We hypothesize that the dichotomous outcomes will be statistically fragile, and higher fragility will exist among statistically significant outcomes comparable to other orthopedic specialties. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), randomized controlled trials from 4 orthopedic journals indexed on PubMed from 2000 to 2022 reporting dichotomous measures relating to distal biceps tendon repairs were included. The fragility index (FI) of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The fragility quotient (FQ) was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 1038 articles screened, 7 RCTs containing 24 dichotomous outcomes were included for analysis. The fragility index and fragility quotient of all outcomes was 6.5 (IQR 4-9) and 0.077 (IQR 0.031-0.123), respectively. However, statistically significant outcomes had a fragility index and fragility quotient of 2 (IQR 2-7) and 0.036 (IQR 0.025-0.091), respectively. The average number of patients lost to follow-up was 2.7 patients, with 28.6% of the included studies reporting loss to follow-up (LTF) greater than or equal to 6.5. CONCLUSIONS: The literature surrounding distal biceps tendon repair may not be as stable as previously thought and presents a similar fragility index to other orthopedic subspecialties. We therefore recommend triple reporting the P value, fragility index, and fragility quotient to aid in the interpretation of clinical findings reported in biceps tendon repair literature.

American Shoulder and Elbow Surgeons SLAP/Biceps Anchor Study Group evidence review: pathoanatomy and diagnosis in clinically significant labral injuries.

Glenoid superior biceps-labral pathology diagnosis, treatment, and outcomes are an evolving area of shoulder surgery. Historically, described as superior labrum anterior posterior (SLAP) tears, these lesions were identified as a source of pain in throwing athletes. Diagnosis and treatments applied to these SLAP lesions resulted in less than optimal outcomes in some patients and a prevailing sense of confusion. The purpose of this paper is to perform a reappraisal of the anatomy, examination, imaging, and diagnosis by the American Shoulder and Elbow Surgeons/SLAP biceps study group. We sought to capture emerging concepts and suggest a more unified approach to evaluation and identify specific needs for future research.

The Fragility of Tourniquet Use in Total Knee Arthroplasty: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Physicians utilize P-values to interpret clinical trial data and guide patient-care decisions. Fragility analysis assesses the stability of statistical findings in relation to outcome event reversals. This study assessed the statistical fragility of recent randomized controlled trials (RCTs) investigating tourniquet use in total knee arthroplasty (TKA). METHODS: We queried PubMed, EMBASE, and MEDLINE for RCTs comparing outcomes in TKA based on tourniquet use. Fragility index (FI) and reverse fragility index (reverse FI) were calculated - for significant and nonsignificant outcomes, respectively - as the number of outcome reversals required to change statistical significance. The fragility quotient (FQ) was calculated by dividing the FI or reverse FI by the sample size. Median overall FI and FQ were calculated for all included outcomes, and sub-analyses were performed by reported significance. The literature search yielded 23 studies reporting 91 total dichotomous outcomes. RESULTS: Overall median FI was 4 with an interquartile range (IQR) of 3 to 6. Overall median FQ was 0.0476 (IQR 0.0291 to 0.0867). A total of 11 outcomes were statistically significant with a median FI and FQ of 2 (IQR 1.5 to 5) and 0.0200 (IQR 0.0148 to 0.0484), respectively. There were 80 outcomes that were nonsignificant with a median reverse FI of 4 (IQR 3 to 6). Loss to follow-up was greater than the median FI in 17.6% of outcomes. CONCLUSION: Altering a small number of outcomes is often sufficient to reverse findings in RCTs evaluating tourniquet use in TKA. We recommend including fragility analyses to increase reliability in the interpretation of study conclusions.

Improving Radiographic Fracture Recognition Performance and Efficiency Using Artificial Intelligence.

Background Missed fractures are a common cause of diagnostic discrepancy between initial radiographic interpretation and the final read by board-certified radiologists. Purpose To assess the effect of assistance by artificial intelligence (AI) on diagnostic performances of physicians for fractures on radiographs. Materials and Methods This retrospective diagnostic study used the multi-reader, multi-case methodology based on an external multicenter data set of 480 examinations with at least 60 examinations per body region (foot and ankle, knee and leg, hip and pelvis, hand and wrist, elbow and arm, shoulder and clavicle, rib cage, and thoracolumbar spine) between July 2020 and January 2021. Fracture prevalence was set at 50%. The ground truth was determined by two musculoskeletal radiologists, with discrepancies solved by a third. Twenty-four readers (radiologists, orthopedists, emergency physicians, physician assistants, rheumatologists, family physicians) were presented the whole validation data set (n = 480), with and without AI assistance, with a 1-month minimum washout period. The primary analysis had to demonstrate superiority of sensitivity per patient and the noninferiority of specificity per patient at -3% margin with AI aid. Stand-alone AI performance was also assessed using receiver operating characteristic curves. Results A total of 480 patients were included (mean age, 59 years ± 16 [standard deviation]; 327 women). The sensitivity per patient was 10.4% higher (95% CI: 6.9, 13.9; P < .001 for superiority) with AI aid (4331 of 5760 readings, 75.2%) than without AI (3732 of 5760 readings, 64.8%). The specificity per patient with AI aid (5504 of 5760 readings, 95.6%) was noninferior to that without AI aid (5217 of 5760 readings, 90.6%), with a difference of +5.0% (95% CI: +2.0, +8.0; P = .001 for noninferiority). AI shortened the average reading time by 6.3 seconds per examination (95% CI: -12.5, -0.1; P = .046). The sensitivity by patient gain was significant in all regions (+8.0% to +16.2%; P < .05) but shoulder and clavicle and spine (+4.2% and +2.6%; P = .12 and .52). Conclusion AI assistance improved the sensitivity and may even improve the specificity of fracture detection by radiologists and nonradiologists, without lengthening reading time. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Link and Pedoia in this issue.

Nomogram for Predicting In-Hospital Mortality in Patients with Acute ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock after Primary Percutaneous Coronary Intervention.

Background: Mortality after percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients with cardiogenic shock (CS) remains high. However, the real-world risk factors for mortality in these patients are poorly defined. Objective: The aim of this study is to establish a clinical prognostic nomogram for predicting in-hospital mortality after primary PCI in STEMI patients with CS. Methods: This retrospective, multicenter, observational study included STEMI patients with CS who underwent PCI at 39 hospitals in Hebei Province from January 2018 to December 2019. A multivariate logistic regression model was used to identify the factors associated with in-hospital mortality. These factors were then incorporated into a nomogram and its performance was evaluated by discrimination, calibration, and clinical utility. Results: This study included 274 patients, among whom 179 died in hospital. Sex, random blood glucose on admission, ejection fraction after PCI, no-reflow, and intra-aortic balloon pump (IABP) were independently associated with in-hospital mortality (all P < 0.05). In the training set, the nomogram showed a C-index of 0.819, goodness-of-fit of 0.08, and area under the receiver operating characteristic curve (AUC) of 0.819 (95%CI = 0.759-0.879). In the testing set, the C-index was 0.842, goodness-of-fit was 0.585, and AUC was 0.842 (95%CI = 0.715-0.970). The results indicate that the nomogram had good discrimination and good prediction accuracy and could achieve a good net benefit. Conclusion: We established and validated a nomogram that provided individual prediction of in-hospital mortality for STEMI patients with CS after PCI in a Chinese population.

Pou3f1 mediates the effect of Nfatc3 on ulcerative colitis-associated colorectal cancer by regulating inflammation.

BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is an important complication of ulcerative colitis. Pou3f1 (POU class 3 homeobox 1) is a critical regulator for developmental events and cellular biological processes. However, the role of Pou3f1 in the development of UC-CRC is unclear. METHODS: In vivo, a UC-CRC mouse model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). Body weight, colon length, mucosal damage, tumor formation, and survival rate were assessed to determine the progression of UC-CRC. Western blot, quantitative real-time PCR, ELISA, immunohistochemistry, immunofluorescence and TUNEL were performed to examine the severity of inflammation and tumorigenesis. In vitro, LPS-treated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 cells were used to study the role of Pou3f1 in inflammation. ChIP and luciferase reporter assays were used to confirm the interaction between Nfatc3 and Pou3f1. RESULTS: Pou3f1 expression was increased in the colons of UC-CRC mice, and its inhibition attenuated mucosal injury, reduced colon tumorigenesis and increased survival ratio. Knockdown of Pou3f1 suppressed cell proliferation and increased cell death in colon tumors. Both the in vivo and in vitro results showed that Pou3f1 depletion reduced the production of proinflammation mediators. In addition, ChIP and luciferase reporter assays demonstrated that Nfatc3 directly bound with the Pou3f1 promoter to induce its expression. The effect of Nfatc3 on the inflammatory response in macrophages was suppressed by Pou3f1 knockdown. CONCLUSION: Overall, it outlines that Pou3f1 mediates the role of Nfatc3 in regulating macrophage inflammation and carcinogenesis in UC-CRC development.

Update: Posttreatment Imaging of the Knee after Cartilage Repair.

Focal cartilage lesions are common pathologies at the knee joint that are considered important risk factors for the premature development of osteoarthritis. A wide range of surgical options, including but not limited to marrow stimulation, osteochondral auto- and allografting, and autologous chondrocyte implantation, allows for targeted treatment of focal cartilage defects. Arthroscopy is the standard of reference for the assessment of cartilage integrity and quality before and after repair. However, deep cartilage layers, intrachondral composition, and the subchondral bone are only partially or not at all visualized with arthroscopy. In contrast, magnetic resonance imaging offers noninvasive evaluation of the cartilage repair site, the subchondral bone, and the soft tissues of the joint pre- and postsurgery. Radiologists need to be familiar with the different surgical procedures available and their characteristic postsurgical imaging appearances to assess treatment success and possible complications adequately. We provide an overview of the most commonly performed surgical procedures for cartilage repair at the knee and typical postsurgical imaging characteristics.

Assessing the hospital volume-outcome relationship in total elbow arthroplasty.

BACKGROUND: Total elbow arthroplasty (TEA) is an effective intervention for multiple elbow disorders including complex fracture in elderly patients, post-traumatic arthropathy, inflammatory arthropathy, and distal humeral nonunion. Given its known therapeutic value and low utilization rate, an investigation into the thresholds for TEA institutional volume-outcome relationships is warranted. The purpose of this study was to identify TEA volume thresholds that serve as predictors of institutional outcomes including complications, readmissions, revisions, cost of care, length of stay (LOS), and non-home discharge. We hypothesized that increased institutional volume would be associated with decreased 90-day adverse outcomes and resource utilization. METHODS: The Nationwide Readmission Database was queried from 2010 to 2017 to identify all cases of TEA. Hospital volume was calculated using a unique hospital identifier and divided into quartiles. Outcomes such as complications, readmissions, revisions, cost of care, LOS, and non-home discharge were then analyzed by quartile. The same outcomes were assessed via stratum-specific likelihood ratio (SSLR) analysis to define volume strata among institutions. RESULTS: SSLR analysis defined statistically significant hospital volume categories for each 90-day outcome. The volume category with the lowest complication rate was ≥21 TEAs per year (5.6%). The volume categories with the lowest readmission rates were 1-3 TEAs per year (4.7%) and ≥18 TEAs per year (9.2%). Revision rates were lowest in the volume categories of 1-5 TEAs per year (0.1%) and ≥18 TEAs per year (0.1%). Hospitals with ≥21 TEAs per year had the lowest cost of care and the highest rate of extended LOS (>2 days). SSLR analysis showed that non-home discharges decreased in a stepwise manner as volume increased. The lowest non-home discharge rate was associated with the volume category of ≥22 TEAs per year (20.3%). CONCLUSION: This study defines TEA volume strata for institutional outcomes. The highest TEA volume strata were associated with the lowest rates of 90-day complications, revisions, and non-home discharges and the lowest cost of care. This trend is likely attributable to the benefits of high-volume institutional experience and standardized patient-care processes.