Pandemic-associated pernio harbors footprints of an abortive SARS-CoV-2 infection.

Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.

Enhancing radiology training with GPT-4: Pilot analysis of automated feedback in trainee preliminary reports.

RATIONALE AND OBJECTIVES: Radiology residents often receive limited feedback on preliminary reports issued during independent call. This study aimed to determine if Large Language Models (LLMs) can supplement traditional feedback by identifying missed diagnoses in radiology residents' preliminary reports. MATERIALS & METHODS: A randomly selected subset of 500 (250 train/250 validation) paired preliminary and final reports between 12/17/2022 and 5/22/2023 were extracted and de-identified from our institutional database. The prompts and report text were input into the GPT-4 language model via the GPT-4 API (gpt-4-0314 model version). Iterative prompt tuning was used on a subset of the training/validation sets to direct the model to identify important findings in the final report that were absent in preliminary reports. For testing, a subset of 10 reports with confirmed diagnostic errors were randomly selected. Fourteen residents with on-call experience assessed the LLM-generated discrepancies and completed a survey on their experience using a 5-point Likert scale. RESULTS: The model identified 24 unique missed diagnoses across 10 test reports with i% model prediction accuracy as rated by 14 residents. Five additional diagnoses were identified by users, resulting in a model sensitivity of 79.2 %. Post-evaluation surveys showed a mean satisfaction rating of 3.50 and perceived accuracy rating of 3.64 out of 5 for LLM-generated feedback. Most respondents (71.4 %) favored a combination of LLM-generated and traditional feedback. CONCLUSION: This pilot study on the use of LLM-generated feedback for radiology resident preliminary reports demonstrated notable accuracy in identifying missed diagnoses and was positively received, highlighting LLMs' potential role in supplementing conventional feedback methods.

Analysis of percutaneous nephrostomy exchange intervals: insights from a retrospective Merative MarketScan analysis between 2009-2021.

BACKGROUND: Current practices in nephrostomy exchange are guided by institutional or societal expert-consensus rather than evidence-based recommendations. OBJECTIVE: To examine the temporal distribution of exchanges and assess whether the observed distributions align with institutional, or expert-recommended guidelines where routine exchanges would be expected to occur within 60-89 days. Non-routine exchanges would be expected to occur either after 60 days or after 89 days. METHODS: Data were collected from the Merative™ MarketScan Commercial Claims and Encounters Databases and included all patients who underwent a PCN exchange from 2009 to 2021. The dataset was queried using ICD-9/10 and CPT coding systems. Outpatient exchanges were classified as routine exchanges, whereas inpatient exchanges were classified as non-routine exchanges. Chi-Square Goodness-of-Fit tests were used to compare observed frequencies against expected distributions of routine exchanges within the 59-89 day window, and non-routine exchanges to occur after either 60 or after 89 days. RESULTS: There was a total of 19,689 exchanges: of those, 41% (n = 8,058) exchange encounters occurred within 29 days, 67% (n = 13,213) occurred within 59 days, and 81% (n = 15,899) occurred within 89 days. Routine exchanges accounted for 76% of total exchanges: of those routine exchanges, 39% (n = 5,863) of routine exchanges occurred within 29 days, 67% (n = 10,057) occurred within 59 days, and 82% (n = 12,256) occurred within 89 days. Non-routine exchanges account for 24% of all exchanges in the study cohort. Of all non-routine exchanges (n = 4,737), 46% (n = 2,035) of non-routine exchange encounters occurred within 29 days, 67% (n = 3,156) within 60 days, and 77% (n = 3,643) within 89 days. Chi-square tests indicated significant deviations from the expected distributions for both routine (p < 0.01) and non-routine (p < 0.01) exchanges. CONCLUSION: A significant proportion of routine exchanges occur outside a 60-89 day window, and with a majority of routine exchange observations occurring prior to 59 days. A significant proportion of non-routine exchanges occur prior to 60 days and prior to 89 days. CLINICAL IMPACT: Significant disparities between existing guidelines and clinical practice, underscoring the need for evidence-based guidelines to reduce complication rates, improve patient outcomes, and reduce the burden of cost on the healthcare system.

Towards inclusive biodesign and innovation: lowering barriers to entry in medical device development through large language model tools.

In the following narrative review, we discuss the potential role of large language models (LLMs) in medical device innovation, specifically examples using generative pretrained transformer-4. Throughout the biodesign process, LLMs can offer prompt-driven insights, aiding problem identification, knowledge assimilation and decision-making. Intellectual property analysis, regulatory assessment and market analysis emerge as key LLM applications. Through case examples, we underscore LLMs' transformative ability to democratise information access and expertise, facilitating inclusive innovation in medical devices as well as its effectiveness with providing real-time, individualised feedback for innovators of all experience levels. By mitigating entry barriers, LLMs accelerate transformative advancements, fostering collaboration among established and emerging stakeholders.

Precision soft tissue balancing: grid-assisted pie-crusting in total knee arthroplasty.

Introduction: The varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release. Methods: Cadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed. Results: A total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm-7.078 ± 1.414 mm (R2 = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm (R2 = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm-4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm-25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed (R2 = 0.988). Discussion: Our results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees.

Distal Femur Valgus Deformity After Rigid Intramedullary Nailing of Adolescent Femoral Shaft Fracture.

A 12-year-old girl developed a distal femoral shaft fracture treated with lateral trochanteric entry intramedullary nail fixation. The nail was retained after union because of a persistent nonossifying fibroma at the previous fracture site. At 16 months after surgery, marked valgus deformity was noted at the distal femur, with signs of implant haloing and loosening, suggesting repetitive motion and stress concentration of forces at the distal femur. Owing to recognition before skeletal maturity, the valgus was corrected with hemiepiphysiodesis. This finding illustrates the importance of follow-up up to skeletal maturity for pediatric femoral shaft fractures and consideration of routine removal of implants after fracture union to avoid this previously unreported complication.

Decoding radiology reports: Potential application of OpenAI ChatGPT to enhance patient understanding of diagnostic reports.

PURPOSE: To evaluate the complexity of diagnostic radiology reports across major imaging modalities and the ability of ChatGPT (Early March 2023 Version, OpenAI, California, USA) to simplify these reports to the 8th grade reading level of the average U.S. adult. METHODS: We randomly sampled 100 radiographs (XR), 100 ultrasound (US), 100 CT, and 100 MRI radiology reports from our institution's database dated between 2022 and 2023 (N = 400). These were processed by ChatGPT using the prompt "Explain this radiology report to a patient in layman's terms in second person: ". Mean report length, Flesch reading ease score (FRES), and Flesch-Kincaid reading level (FKRL) were calculated for each report and ChatGPT output. T-tests were used to determine significance. RESULTS: Mean report length was 164 ± 117 words, FRES was 38.0 ± 11.8, and FKRL was 10.4 ± 1.9. FKRL was significantly higher for CT and MRI than for US and XR. Only 60/400 (15%) had a FKRL <8.5. The mean simplified ChatGPT output length was 103 ± 36 words, FRES was 83.5 ± 5.6, and FKRL was 5.8 ± 1.1. This reflects a mean decrease of 61 words (p < 0.01), increase in FRES of 45.5 (p < 0.01), and decrease in FKRL of 4.6 (p < 0.01). All simplified outputs had FKRL <8.5. DISCUSSION: Our study demonstrates the effective use of ChatGPT when tasked with simplifying radiology reports to below the 8th grade reading level. We report significant improvements in FRES, FKRL, and word count, the last of which requires modality-specific context.

Characteristics of pivotal clinical trials of FDA-approved endovascular devices between 2000 and 2018: An interrupted time series analysis.

Background: The Food and Drug Administration (FDA) reviews safety, efficacy, and the quality of medical devices through its regulatory process. The FDA Safety and Innovation Act (FDASIA) of 2012 was aimed at accelerating the regulatory process for medical devices. Objectives: The purpose of our study was to (1) quantify characteristics of pivotal clinical trials (PCTs) supporting the premarket approval of endovascular medical devices and (2) analyze trends over the last two decades in light of the FDASIA. Methods: We surveyed the study designs of endovascular devices with PCTs from the US FDA pre-market approval medical devices database. The effect of FDASIA on key design parameters (e.g., randomization, masking, and number of enrolled patients) was estimated using an interrupted time series analysis (segmented regression). Results: We identified 117 devices between 2000-2018. FDASIA was associated with a decrease in double blinding (p < 0.0001) and a decrease in historical comparators (p < 0.0001). Discussion: Our results reveal an overall trend of decreased regulatory requirements as it relates to clinical trial characteristics, but a compensatory increased rate of post-approval across device classes. Furthermore, there was an emphasis on proving equivalence or non-inferiority rather than more use of active comparators in clinical trials. Medical device stakeholders, notably clinicians, must be aware of the shifting regulatory landscape in order to play an active role in promoting patient safety.

Impact of drainage catheter material, size, and anti-dislodgement mechanism on percutaneous nephrostomy exchange intervals: a systematic review protocol.

Background: Percutaneous nephrostomy (PCN) is a commonly performed procedure by interventional radiology and urology to treat urinary obstruction. In this procedure, a catheter is percutaneously placed into the renal pelvis for urinary diversion or hemorrhagic cystitis. Material type, catheter size, and catheter shape (anti-dislodgement feature) ultimately contribute to the inherent traits of longevity in drainage catheter device. Reviewing the relative strengths or weaknesses of products in the existing clinical market may help clinicians critically appraise the devices they use with evidence-based findings from this review. Furthermore, a deeper understanding of the relative strengths and weaknesses of existing devices may help inform the next generation of drainage catheter devices to prolong the interval between exchanges without detriment to patient safety. Methods: The following electronic databases will be queried: PubMed, Web of Science, Cochrane from their inception to January 2023 to identify randomized controlled trials (RCTs) and cohort studies to investigate the differences that our interventions of catheter material, size, and dislodgement mechanism will have on the exchange interval (standard of care 90 days vs. 60 days vs. 45 days vs. 30 days). The primary outcomes will be the drainage catheter exchange frequency. Ethics and dissemination: We aim to share our findings through high-impact peer reviewed journals. As drainage catheters and minimally invasive interventional radiology procedures become more popular, it is important for healthcare providers taking case of these populations to understand which variables might optimize patient care and minimize emergent exchanges. Data will be made available to readers. Registration: PROSPERO ( CRD42023432788, 16 June 2023).

Esophageal Achalasia: From Laparoscopic to Robotic Heller Myotomy and Dor Fundoplication.

Objective: Laparoscopic Heller myotomy and Dor fundoplication has become the gold standard in treating esophageal achalasia and robotic surgical platform represents its natural evolution. The objective of our study was to assess durable long-term clinical outcomes in our cohort. Methods and Procedures: Between June 1, 1999 and June 30, 2019, 111 patients underwent minimally invasive treatment for achalasia (96 laparoscopically and 15 robotically). Fifty-two were males. Mean age was 49 years (20 - 96). Esophageal manometry confirmed the diagnosis. Fifty patients underwent pH monitoring study, with pathologic reflux in 18. Preoperative esophageal dilation was performed in 76 patients and 21 patients received botulin injection. Dysphagia was universally present, and mean duration was 96 months (5 - 480). Results: Median operative time was 144 minutes (90 - 200). One patient required conversion to open approach. Four mucosal perforations occurred in the laparoscopic group and were repaired intraoperatively. Seven patients underwent completion esophageal myotomy and added Dor fundoplication. Upper gastrointestinal series was performed before discharge. Median hospital stay was 39 hours (24 - 312). Median follow up was 157 months (6 - 240), and dysphagia was resolved in 94% of patients. Seven patients required postoperative esophageal dilation. Conclusions: Minimally invasive Heller myotomy and Dor fundoplication are feasible. The operation is challenging, but excellent results hinge on the operative techniques and experience. The high dexterity, three-dimensional view, and the ergonomic movements of robotic surgery allow application of all the technical elements, achieving the best durable outcome for the patient. Robotic surgery is the natural evolution of minimally invasive treatment of esophageal achalasia.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Pernio and early SARS-CoV-2 variants: natural history of a prospective cohort and the role of interferon.

Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.

Surgical resection, radiotherapy and percutaneous thermal ablation for treatment of stage 1 non-small cell lung cancer: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Currently, surgical resection is the gold standard of treatment. However, as patients are becoming medically more complex presenting with advanced disease, minimally invasive image-guided percutaneous ablations are gaining popularity. Therefore, comparison of surgical, ablative and second-line external beam therapies will help clinicians, as management of NSCLC changes. We will conduct a meta-analysis, reviewing literature investigating these therapies in adult patients diagnosed with stage 1 NSCLC, with neither hilar nor mediastinal nodal involvement, confirmed either through cytology or histology regardless of type. METHODS AND ANALYSIS: We will search electronic databases (MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, Cochrane) from their inception to January 2021 to identify randomised controlled trials (RCTs), cluster RCTs and cohort studies comparing survival and clinical outcomes between any two interventions (lobectomy, wedge resection, video-assisted thoracoscopic surgery/robot-assisted thoracoscopic surgery, radiofrequency ablation, microwave ablation, cryoablation and consolidated radiation therapies (external beam radiation therapy, stereotactic body radiation therapy, and 3D conformal radiation therapy). The primary outcomes will include cancer-specific survival, lung disease-free survival, locoregional recurrence, death, toxicity and non-target organ injury. We will also search published and unpublished studies in trial registries and will review references of included studies for possible inclusion. Risk of bias will be assessed using tools developed by the Cochrane collaboration. Two reviewers will independently assess the eligibility of studies and conduct the corresponding risk of bias assessments. For each outcome, given enough studies, we will conduct a network meta-analysis. Finally, we will use the Confidence in Network Meta-Analysis tool to assess quality of the evidence for each of the primary outcomes. ETHICS AND DISSEMINATION: We aim to share our findings through high-impact peer review. As interventional techniques become more popular, it will be important for providers in multidisciplinary teams caring for these patients to receive continuing medical education related to these interventions. Data will be made available to readers. PROSPERO REGISTRATION NUMBER: CRD42021276629.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as "COVID toes", remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients. Summary: NET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.

Acetazolamide enhanced drug-eluting beads: manipulating the hepatocellular carcinoma microenvironment.

Hepatocellular carcinoma (HCC) is the most common type of primary liver malignancy. Intra-arterial therapies such as drug-eluting bead transarterial chemoembolization (DEB-TACE) can be effective forms of locoregional treatment for HCC. Solid liver tumors such as HCC promote a biochemical tumor microenvironment (TME) that allows tumor recurrence. The TME creates an environmental acidic pH, which induces chemotherapy resistance and immunosuppression. To address TME acidity, pharmacological agents like acetazolamide could be combined with primary transarterial therapies to optimize HCC treatment. We present a case of a 51-year-old male with a history of alcoholic cirrhosis and recently diagnosed HCC who underwent DEB-TACE with acetazolamide, resulting in complete tumor response on 1.5, 4.5, and 7.5 months follow-up.

From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio.

Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets.