Comparing MRI and arthroscopic appearances of common knee pathologies: A pictorial review.

Knee pathology, including anterior cruciate ligament (ACL) tears, meniscal tears, articular cartilage lesions, and intra-articular masses or cysts are common clinical entities treated by orthopedic surgeons with arthroscopic surgery. Preoperatively, magnetic resonance imaging (MRI) is now standard in confirming knee pathology, particularly detecting pathology less evident with history and physical examination alone. The radiologist's MRI interpretation becomes essential in evaluating intra-articular knee structures. Typically, the radiologist that interprets the MRI does not have the opportunity to view the same pathology arthroscopically. Thus, the purpose of this article is to illustratively reconcile what the orthopedic surgeon sees arthroscopically with what the radiologist sees on magnetic resonance imaging when viewing the same pathology. Correlating virtual and actual images can help better understand pathology, resulting in more accurate MRI interpretations. In this article, we present and review a series of MR and correlating arthroscopic images of ACL tears, meniscal tears, chondral lesions, and intra-articular masses and cysts. Short teaching points are included to highlight the importance of radiological signs and pathological MRI appearance with significant clinical and arthroscopic findings.

Linear ubiquitin chains remodel the proteome and influence the levels of hundreds of regulators in Drosophila.

Ubiquitin controls many cellular processes via its post-translational conjugation onto substrates. Its use is highly variable due to its ability to form poly-ubiquitin with various topologies. Among them, linear chains have emerged as important regulators of immune responses and protein degradation. Previous studies in Drosophila melanogaster found that expression of linear poly-ubiquitin that cannot be dismantled into single moieties leads to their own ubiquitination and degradation or, alternatively, to their conjugation onto proteins. However, it remains largely unknown which proteins are sensitive to linear poly-ubiquitin. To address this question, here we expanded the toolkit to modulate linear chains and conducted ultra-deep coverage proteomics from flies that express non-cleavable, linear chains comprising 2, 4, or 6 moieties. We found that these chains regulate shared and distinct cellular processes in Drosophila by impacting hundreds of proteins. Our results provide key insight into the proteome subsets and cellular pathways that are influenced by linear poly-ubiquitin with distinct lengths and suggest that the ubiquitin system is exceedingly pliable.

Accelerated Stability Assessment of Extemporaneously Compounded Amiloride Nasal Spray.

Amiloride is a U.S. Food and Drug Administration-approved diuretic agent used to treat hypertension and congestive heart failure. Recent human and animal studies have suggested that amiloride may also have a role in treating anxiety through its acid-sensing ion channel antagonism. Intranasal administration of amiloride nasal spray via an extemporaneously compounded preparation has the potential for rapid delivery to the site of action to achieve therapeutic outcomes in individual patients with anxiety disorders. However, these patient-specific preparations do not have the pre-formulation characterization, including chemical stability, that conventional manufactured dosage forms have. The objective of this study was to assess the estimated chemical stability of compounded amiloride nasal spray over 6 months and 12 months utilizing accelerated degradation with high heat and the Arrhenius equation. A stability-indicating highperformance liquid chromatography analytical method was employed at appropriate intervals over a 12-month period to reveal that amiloride remained chemically stable over the period tested and by extrapolation. Physical stability and compatibility with the preservative benzyl alcohol were also confirmed via visual inspection, pH monitoring, and measurement of turbidity.

Antibullying Interventions in Schools: Assessing the Evidence Base.

OBJECTIVE: This systematic review used established rating criteria to describe the level of evidence for interventions aimed at preventing or reducing bullying perpetration and victimization in schools, synthesized the evidence for students from racially and ethnically diverse backgrounds, and reviewed the literature for available information to conduct an economic analysis of the interventions. METHODS: Major databases, gray literature, and evidence-base registries were searched to identify studies published from 2008 through 2022. The authors rated antibullying intervention models as having high, moderate, or low evidence depending on the number and rigor of studies with positive findings. RESULTS: Overall, 80 articles reporting on 71 original research studies describing a total of 48 antibullying interventions met the inclusion criteria for this review. Two schoolwide interventions received a high-evidence rating: the KiVa (Kiusaamista Vastaan) Antibullying Program and the Friendly Schools program. Multilevel interventions with components at the levels of school, classroom, and individual student most consistently showed strong evidence for reducing bullying behavior in elementary and middle school grades. Four interventions yielded positive effects in reducing bullying and victimization among diverse samples of students. CONCLUSIONS: Antibullying interventions can reduce bullying in schools. Some interventions show effectiveness with students from racially and ethnically diverse backgrounds. The gains relative to per-student costs were in the range that is considered cost-effective. Most implementation costs are spent on staff training and support. Research on successful implementation of whole-school interventions and additional synthesis of evidence pertaining to program structures would further advance the antibullying evidence base.

Assessing the Evidence Base for School-Based Promotion and Prevention Interventions: Introduction to the Series.

Schools are an important component in the mental health system of care for youths. Teachers and other school staff have unique opportunities to promote emotional wellness and prevent mental health conditions. Although numerous programs are available, identifying evidence-based and effective options is a significant challenge. This introduction lays out the rationale and methodology of the Assessing the Evidence Base (AEB) Series, a collection of systematic reviews of school-based mental health promotion and prevention approaches recommended by the National Academies of Sciences, Engineering, and Medicine for students in kindergarten through grade 12. Authors of the current AEB Series used the rating criteria derived from the 2014 AEB Series, which provided systematic reviews of a wide spectrum of interventions for mental and substance use disorders. Like its predecessor, the current series upholds a high standard of scientific rigor while ensuring that the information is easily accessible to various stakeholders in education, behavioral health, and communities. It describes the universal features included in each systematic review, such as a rating of the level of evidence for interventions, intervention program components, identification of interventions that have yielded positive outcomes for students from underserved populations, and a review of cost data. The AEB systematic reviews will serve as an important tool for decision makers involved in managing limited resources for various programs in school-based mental health services by synthesizing large bodies of research for use by leaders in education and behavioral health.

Reducing Disruptive and Distracting Behaviors in the Classroom: Assessing the Evidence Base.

OBJECTIVE: Disruptive and distracting behaviors in the classroom, from off-task to aggressive behaviors, negatively affect academic engagement and achievement and can lead to more serious problems, including mental health conditions and substance use disorders. The goals of this systematic review were to assess the level of evidence, using established rating criteria, for interventions aimed at preventing or reducing disruptive and distracting classroom behaviors; identify program components common to multiple interventions; synthesize the evidence in regard to students from different racial-ethnic groups; and conduct an economic analysis of these interventions. METHODS: A search of major databases, gray literature, and evidence base registries was conducted to identify studies published between 2008 and 2022. The authors rated interventions as having high, moderate, or low levels of evidence of effectiveness on the basis of the number and rigor of studies with positive outcomes. RESULTS: Of the 27 interventions identified across 65 studies (N=73 articles), six interventions received a high or moderate evidence rating. The Good Behavior Game was the most frequently studied intervention. Many interventions shared similar program components, including behavioral management, classroom management, emotional-cognitive processes, and skills acquisition. Most articles (86%) were focused on elementary school students. The four interventions rated as having high evidence of effectiveness also showed generally positive outcomes in studies conducted in school settings with racial-ethnic diversity. No studies met the criteria for inclusion in an economic analysis. CONCLUSIONS: With greater use and more research, interventions focusing on reducing disruptive and distracting behaviors have the potential to promote student well-being and prevent mental health conditions.

The Role of Artificial Intelligence in the Identification and Evaluation of Bone Fractures.

Artificial intelligence (AI), particularly deep learning, has made enormous strides in medical imaging analysis. In the field of musculoskeletal radiology, deep-learning models are actively being developed for the identification and evaluation of bone fractures. These methods provide numerous benefits to radiologists such as increased diagnostic accuracy and efficiency while also achieving standalone performances comparable or superior to clinician readers. Various algorithms are already commercially available for integration into clinical workflows, with the potential to improve healthcare delivery and shape the future practice of radiology. In this systematic review, we explore the performance of current AI methods in the identification and evaluation of fractures, particularly those in the ankle, wrist, hip, and ribs. We also discuss current commercially available products for fracture detection and provide an overview of the current limitations of this technology and future directions of the field.

Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes.

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention.

The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, and became moribund. Lung tissues from these mice and bronchoalveolar lavage and lung tissues from patients with COVID-19 showed elevated levels of hyaluronic acid (HA), HA-family members, an inflammatory signature, and immune cell infiltration. 4-methylumbelliferone (4-MU), an oral drug for biliary-spasm treatment, inhibits HA-synthesis. At the human equivalent dose, 4-MU prevented/inhibited COVID-19-like pathologies and long-term morbidity; 4-MU and metabolites accumulated in mice lungs. Therefore, these versatile SARS-COV-2 ribo-oligonucleotide oropharyngeal models recapitulate COVID-19 pathology, with HA as its critical mediator and 4-MU as a potential therapeutic for COVID-19.

Circumferential resection margin rates in esophageal cancer resection- oncological equivalency and comparable clinical outcomes between open versus minimally invasive techniques: A retrospective cohort study.

BACKGROUND: Radical surgery for esophageal cancer requires macroscopic and microscopic clearance of all malignant tissue. A critical element of the procedure is achieving a negative circumferential margin (CRM) to minimize local recurrence. The utility of minimally invasive surgery poses challenges in replicating techniques developed in open surgery, particularly for hiatal dissection in esophago-gastrectomy. In this study, the technical approach and clinical and oncological outcomes for open and laparoscopic esophago-gastrectomy are described with particular reference to CRM involvement. MATERIALS AND METHODS: This cohort study included all patients undergoing either open or laparoscopic esophago-gastrectomy between January 2004 to June 2022 in a single tertiary center. A standard surgical technique for hiatal dissection of the esophago-gastric junction developed in open surgery was adapted for a laparoscopic approach. Clinical parameters, length of stay (LOS), post-operative complications and mortality data were collected and analyzed by a Mann-Whitney U or Fisher's exact method. RESULTS: Overall 447 patients underwent an esophago-gastrectomy in the study with 219 open and 228 laparoscopic procedures. The CRM involvement was 18.8% in open surgery and 13.6% in laparoscopic surgery. The 90-day-mortality for open surgery was 4.1% compared with 2.2% for laparoscopic procedures. Median Intensive care unit (ITU), inpatient LOS and 30-day readmission rates were shorter for laparoscopic compared with open esophago-gastrectomy (ITU: 5 versus 8 days, P=0.0004; LOS: 14 versus 20 days, P=0.022; 30-day re-admission 7.46% versus 10.50%). Post-operative complication rates were comparable across both cohorts. The rates of starting adjuvant chemotherapy were 51.8% after open and 74.4% in laparoscopic esophago-gastrectomy. CONCLUSION: This study presents a standardized surgical approach to hiatal dissection for esophageal cancer. We present equivalence between open and laparoscopic esophago-gastrectomy in clinical, oncological and survival outcomes with similar rates of CRM involvement. We also observe a significantly shorter hospital length of stay with the minimally invasive approach.

Calcific bursitis of the Gruberi bursa: a case report.

BACKGROUND: Bursitis is the inflammation of a synovial bursa, a small synovial fluid-filled sac that acts as a cushion between muscles, tendons, and bones. Further, calcific bursitis results from calcium deposits on the synovial joint that exacerbates pain and swelling. The Gruberi bursa is located dorsolaterally in the ankle, between the extensor digitorium longus and the talus. Despite limited literature on its pathophysiology, the aim of this case is to discuss the bursa's association with calcific bursitis and its management via a case presented to our clinic. CASE PRESENTATION: A 47-year-old Caucasian female with no past medical or family history presents with acute right ankle pain following a minor injury 3 months prior with no improvement on analgesic or steroid therapy. Imaging demonstrated incidental calcium deposits. The day prior to presentation, the patient stated she used 1-pound ankle weights that resulted in mild swelling and gradual pain to the right dorsoanterior ankle. Physical exam findings displayed a significant reduction in the range of motion limited by pain. Imaging confirmed calcification within the capsule of the talonavicular joint, consistent with Gruberi bursitis. Initial management with prednisone yielded minimal improvement, requiring an interventional approach with ultrasound-guided barbotage that elicited immediate improvement. CONCLUSION: The presented case report highlights a rare and unique instance of acute ankle pain and swelling caused by calcific Gruberi bursitis in a young female. Although the Gruberi bursa is a relatively new discovery, it contains inflammatory components that may predispose it to calcification and should be considered in the differential of ankle swelling. Therefore, utilizing a systematic approach to a clinical presentation and considering all differential diagnoses is essential.

Return to Play After Hook of Hamate Fracture: A Systematic Review and Meta-Analysis.

In athletes, a hook of hamate fracture is concerning in terms of time to return to sport and effect on performance upon return. This study aims to analyze the treatment of hook of hamate fractures in athletes to determine their rates of return to play, timelines of recovery, and performance level upon return to play. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to perform this analysis. The PubMed database was queried to perform the literature search. Data were pooled and analyzed. P values <.05 were considered significant. Data were analyzed using the Comprehensive Meta-Analysis software to determine heterogeneity. Twenty studies with 823 patients sustaining hook of hamate fractures that reported any competitive level of play were included in the analysis. Of the 823 patients, 778 (94.5%) were able to return to play with 91.2% (506/555) of patients demonstrating similar or improved performance. The mean time to return to play was 45 days (range: 21-168 days). Treatment included surgical excision for 787 patients (95.6%), open reduction and internal fixation for 18 patients (2.2%), stress reduction/casting for 13 patients (1.6%), and loss to follow-up or surgery refusal for 5 patients (0.6%). A very high number of athletes return to play following a hook of hamate fracture at the same or improved level of performance. In our study, the majority of injuries were treated with surgical excision of the fractured hook of hamate fragment. Most athletes returned to their sport at an average of 45 days.

Question answering systems for health professionals at the point of care-a systematic review.

OBJECTIVES: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. MATERIALS AND METHODS: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology, and forward and backward citations on February 7, 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. RESULTS: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. DISCUSSION: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

Summary of a consensus conference on heart-liver transplantation.

Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multiorgan transplantation were also debated. The findings and consensus statements are presented.

Cost-effectiveness of goal-directed and outcome-based financial incentives for weight loss in low-income populations: the FIReWoRk randomized clinical trial.

BACKGROUND: The Financial Incentives for Weight Reduction (FIReWoRk) clinical trial showed that financial incentive weight-loss strategies designed using behavioral economics were more effective than provision of weight-management resources only. We now evaluate cost-effectiveness. METHODS: Cost-effectiveness analysis of a multisite randomized trial enrolling 668 participants with obesity living in low-income neighborhoods. Participants were randomized to (1) goal-directed incentives (targeting behavioral goals), (2) outcome-based incentives (targeting weight-loss), and (3) resources only, which were provided to all participants and included a 1-year commercial weight-loss program membership, wearable activity monitor, food journal, and digital scale. We assessed program costs, time costs, quality of life, weight, and incremental cost-effectiveness in dollars-per-kilogram lost. RESULTS: Mean program costs at 12 months, based on weight loss program attendance, physical activity participation, food diary use, self-monitoring of weight, and incentive payments was $1271 in the goal-directed group, $1194 in the outcome-based group, and $834 in the resources-only group (difference, $437 [95% CI, 398 to 462] and $360 [95% CI, 341-363] for goal-directed or outcome-based vs resources-only, respectively; difference, $77 [95% CI, 58-130] for goal-directed vs outcome-based group). Quality of life did not differ significantly between the groups, but weight loss was substantially greater in the incentive groups (difference, 2.34 kg [95% CI, 0.53-4.14] and 1.79 kg [95% CI, -0.14 to 3.72] for goal-directed or outcome-based vs resources only, respectively; difference, 0.54 kg [95% CI, -1.29 to 2.38] for goal-directed vs outcome-based). Cost-effectiveness of incentive strategies based on program costs was $189/kg lost in the goal-directed group (95% CI, $124/kg to $383/kg) and $186/kg lost in the outcome-based group (95% CI, $113/kg to $530/kg). CONCLUSIONS: Goal-directed and outcome-based financial incentives were cost-effective strategies for helping low-income individuals with obesity lose weight. Their incremental cost per kilogram lost were comparable to other weight loss interventions.

Does bortezomib influence pre-transplant desensitization therapy or benefit post-heart transplant outcomes for highly sensitized patients?

BACKGROUND: The use of bortezomib which is a proteasome inhibitor has been demonstrated to be efficacious in small number of patients as a desensitization strategy in heart transplant. We reviewed our single center's experience using Bortezomib along with plasmapheresis as desensitization therapy for highly sensitized patients to assess pre- and post-transplant outcomes. METHOD: We assessed 43 highly sensitized patients awaiting HTx (defined as cPRA > 50%) between 2010 and 2021 who underwent desensitization therapy with bortezomib. Only those patients who subsequently underwent HTx were included in this study. Enrolled patients received up to four doses of bortezomib (1.3 mg/m2 ) over 2 weeks in conjunction with plasmapheresis. The efficacy of PP/BTZ was assessed by comparing the calculated panel reactive antibodies to HLA class I or class II antigens. Post-transplant outcomes including overall survival and incidence of rejection were compared to those of non-sensitized patients (PRA < 10%, n = 649) from the same center. RESULTS: The average cPRA prior to PP/BTZ was 94.5%. Post-PP/BTZ there was no statistically significant decline in mean cPRA, class I cPRA, or class II cPRA, though the average percentage decrease in class I cPRA (8.7 ± 17.0%) was higher than the change in class II cPRA (4.4 ± 13.3%). Resulted were also replicated with C1q-binding antibodies showing more effect on I class compared to class II (15.0 ± 37.4% vs. 6.8 ± 33.6%) as well as with 1:8 dilutional assay (14.0 ± 23.0% vs. 9.1 ± 34.9%). Additionally, PP/BTZ treated patients and the control group of non-sensitized patients had similar overall 1 year survival (95.4 vs. 92.5%) but patients with PP/BTZ had increased incidence of AMR (79.1% vs. 97.1%, p = < .001), any treated rejection (62.8% vs. 86.7%, p = < .001) and de novo DSA development (81.4% vs. 92.5%, p = .007). Major side effects of PP/BTZ included thrombocytopenia (42%), infection requiring antibiotics (28%), and neuropathy (12%). CONCLUSION: The use of bortezomib in highly sensitized patients does not significantly lower circulating antibodies prior to heart transplantation. However, its use may improve the chances of obtaining an immuno-compatible donor heart and contribute to acceptable post-transplant outcomes.

The Role of Mucin Expression in the Diagnosis of Oesophago-Gastric Cancer: A Systematic Literature Review.

Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner. Mucins are transmembrane glycoproteins implicated in OGC with potential use as biomarkers of malignant transformation. This systematic review defines the role of mucins in OGC diagnosis. A literature search of MEDLINE, Web of Science, Embase and Cochrane databases was performed following PRISMA protocols for studies published January 1960-December 2022. Demographic data and data on mucin sampling and analysis methods were extracted. The review included 124 studies (n = 11,386 patients). Gastric adenocarcinoma (GAc) was the commonest OG malignancy (n = 101) followed by oesophageal adenocarcinoma (OAc, n = 24) and squamous cell carcinoma (OSqCc, n = 10). Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated. High MUC1 expression correlated with poorer prognosis and metastases in OSqCc. MUC2 expression decreases during progression from healthy mucosa to OAc, causing reduced protection from gastric acid. MUC5AC was upregulated, and MUC6 downregulated in GAc. Mucin expression varies in OGC; changes may be epigenetic or mutational. Profiling upper GI mucin expression in OGC, with pre-malignant, benign and healthy controls may identify potential early diagnostic biomarkers.