Can a reconstruction algorithm in major acetabular bone loss be successful in revision hip arthroplasty?

Aims: The aims of this study were to determine the success of a reconstruction algorithm used in major acetabular bone loss, and to further define the indications for custom-made implants in major acetabular bone loss. Methods: We reviewed a consecutive series of Paprosky type III acetabular defects treated according to a reconstruction algorithm. IIIA defects were planned to use a superior augment and hemispherical acetabular component. IIIB defects were planned to receive either a hemispherical acetabular component plus augments, a cup-cage reconstruction, or a custom-made implant. We used national digital health records and registry reports to identify any reoperation or re-revision procedure and Oxford Hip Score (OHS) for patient-reported outcomes. Implant survival was determined via Kaplan-Meier analysis. Results: A total of 105 procedures were carried out in 100 patients (five bilateral) with a mean age of 73 years (42 to 94). In the IIIA defects treated, 72.0% (36 of 50) required a porous metal augment; the remaining 14 patients were treated with a hemispherical acetabular component alone. In the IIIB defects, 63.6% (35 of 55) underwent reconstruction as planned with 20 patients who actually required a hemispherical acetabular component alone. At mean follow-up of 7.6 years, survival was 94.3% (95% confidence interval 97.4 to 88.1) for all-cause revision and the overall dislocation rate was 3.8% (4 of 105). There was no difference observed in survival between type IIIA and type IIIB defects and whether a hemispherical implant alone was used for the reconstruction or not. The mean gain in OHS was 16 points. Custom-made implants were only used in six cases, in patients with either a mega-defect in which the anteroposterior diameter > 80 mm, complex pelvic discontinuity, and massive bone loss in a small pelvis. Conclusion: Our findings suggest that a reconstruction algorithm can provide a successful approach to reconstruction in major acetabular bone loss. The use of custom implants has been defined in this series and accounts for < 5% of cases.

Combining magnetic resonance fingerprinting with voxel-based morphometric analysis to reduce false positives for focal cortical dysplasia detection.

OBJECTIVE: We aim to improve focal cortical dysplasia (FCD) detection by combining high-resolution, three-dimensional (3D) magnetic resonance fingerprinting (MRF) with voxel-based morphometric magnetic resonance imaging (MRI) analysis. METHODS: We included 37 patients with pharmacoresistant focal epilepsy and FCD (10 IIa, 15 IIb, 10 mild Malformation of Cortical Development [mMCD], and 2 mMCD with oligodendroglial hyperplasia and epilepsy [MOGHE]). Fifty-nine healthy controls (HCs) were also included. 3D lesion labels were manually created. Whole-brain MRF scans were obtained with 1 mm3 isotropic resolution, from which quantitative T1 and T2 maps were reconstructed. Voxel-based MRI postprocessing, implemented with the morphometric analysis program (MAP18), was performed for FCD detection using clinical T1w images, outputting clusters with voxel-wise lesion probabilities. Average MRF T1 and T2 were calculated in each cluster from MAP18 output for gray matter (GM) and white matter (WM) separately. Normalized MRF T1 and T2 were calculated by z-scores using HCs. Clusters that overlapped with the lesion labels were considered true positives (TPs); clusters with no overlap were considered false positives (FPs). Two-sample t-tests were performed to compare MRF measures between TP/FP clusters. A neural network model was trained using MRF values and cluster volume to distinguish TP/FP clusters. Ten-fold cross-validation was used to evaluate model performance at the cluster level. Leave-one-patient-out cross-validation was used to evaluate performance at the patient level. RESULTS: MRF metrics were significantly higher in TP than FP clusters, including GM T1, normalized WM T1, and normalized WM T2. The neural network model with normalized MRF measures and cluster volume as input achieved mean area under the curve (AUC) of .83, sensitivity of 82.1%, and specificity of 71.7%. This model showed superior performance over direct thresholding of MAP18 FCD probability map at both the cluster and patient levels, eliminating ≥75% FP clusters in 30% of patients and ≥50% of FP clusters in 91% of patients. SIGNIFICANCE: This pilot study suggests the efficacy of MRF for reducing FPs in FCD detection, due to its quantitative values reflecting in vivo pathological changes. © 2024 International League Against Epilepsy.

How modular porous metal augments have changed the management of acetabular bone loss at primary or revision total hip arthroplasty.

The advent of modular porous metal augments has ushered in a new form of treatment for acetabular bone loss. The function of an augment can be seen as reducing the size of a defect or reconstituting the anterosuperior/posteroinferior columns and/or allowing supplementary fixation. Depending on the function of the augment, the surgeon can decide on the sequence of introduction of the hemispherical shell, before or after the augment. Augments should always, however, be used with cement to form a unit with the acetabular component. Given their versatility, augments also allow the use of a hemispherical shell in a position that restores the centre of rotation and biomechanics of the hip. Progressive shedding or the appearance of metal debris is a particular finding with augments and, with other radiological signs of failure, should be recognized on serial radiographs. Mid- to long-term outcomes in studies reporting the use of augments with hemispherical shells in revision total hip arthroplasty have shown rates of survival of > 90%. However, a higher risk of failure has been reported when augments have been used for patients with chronic pelvic discontinuity.

Molecular Modeling of Self-Assembling Peptides.

Peptide epitopes mediate as many as 40% of protein-protein interactions and fulfill signaling, inhibition, and activation roles within the cell. Beyond protein recognition, some peptides can self- or coassemble into stable hydrogels, making them a readily available source of biomaterials. While these 3D assemblies are routinely characterized at the fiber level, there are missing atomistic details about the assembly scaffold. Such atomistic detail can be useful in the rational design of more stable scaffold structures and with improved accessibility to functional motifs. Computational approaches can in principle reduce the experimental cost of such an endeavor by predicting the assembly scaffold and identifying novel sequences that adopt said structure. Yet, inaccuracies in physical models and inefficient sampling have limited atomistic studies to short (two or three amino acid) peptides. Given recent developments in machine learning and advances in sampling strategies, we revisit the suitability of physical models for this task. We use the MELD (Modeling Employing Limited Data) approach to drive self-assembly in combination with generic data in cases where conventional MD is unsuccessful. Finally, despite recent developments in machine learning algorithms for protein structure and sequence predictions, we find the algorithms are not yet suited for studying the assembly of short peptides.

Characteristics, surgical treatment, and outcomes of injuries involving the tarsus in greyhounds.

Objective: The first objective of this study was to describe the type of tarsal injuries sustained, surgery performed, and postoperative complications in greyhounds presenting to a single veterinary hospital. An additional objective of the study was to determine the surgical site infection (SSI) and explantation rate, and if any variables were associated with an increased risk of SSI and/or explantation. Animals: 116 greyhounds receiving surgical intervention for a tarsal injury. Proceures: Medical records from a single veterinary referral hospital were reviewed retrospectively. Data retrieved included signalment, details regarding the injury, surgical intervention, concurrent castration, surgical/anesthesia times, postoperative management, time to healing, and postoperative complications. In cases that underwent explantation, cause, time from initial surgery, and risk factors were evaluated. Results: The most frequently diagnosed tarsal injuries were fracture of the central tarsal bone (CTB; 57.8%), calcaneal fracture (56.9%) and proximal intertarsal subluxation (34.5%). The most common injury combination was a CTB fracture with a calcaneal fracture (31.9%). In total 115 (99.1%) survived to discharge. Of these, 46 (40.0%) were diagnosed with an SSI and 59 (51.3%) underwent explantation. The most common indication for explantation was SSI. Concurrent medial and lateral surgical approaches was found to be associated with an increased likelihood of SSI and explantation. Clinical relevance: Practitioners performing surgical intervention for tarsal injuries in greyhounds should be aware of the high SSI rate and likelihood that explantation will be required. This risk is elevated for injuries requiring a bilateral surgical approach.

Effect of screw insertion angle and speed on the incidence of transcortical fracture development in a canine tibial diaphyseal model.

OBJECTIVE: To assess the incidence of transcortical fracture (TCF) development based on screw insertion angle and screw insertion speed. STUDY DESIGN: Cadaveric experimental study. SAMPLE POPULATION: Sixty-six canine tibiae. METHODS: Sixty-six cadaveric tibiae were randomly assigned to one of six groups that varied based on screw insertion angle relative to the pilot hole (0, 5, or 10°) and screw insertion speed (650 or 1350 revolutions per minute [rpm]). Each tibia was mounted in a custom jig. Locking self-tapping screws (3.5 mm) were inserted at varying speeds and insertion angles, based on group assignment. Orthogonal radiographs were evaluated for TCFs. Fisher's exact tests with a Bonferroni correction were performed to evaluate differences in the frequency of TCF between groups. RESULTS: In Group A (0°/650 rpm: control), a 0% TCF rate was observed (n = 0/80). Group B (5°/650 rpm) had a 3.75% TCF rate (n = 3/80). Group C (10°/650 rpm) had a 12.5% TCF rate (n = 10/80). Group D (10°/hand insertion) had a 3.75% TCF rate (n = 3/80). Group E (10°/1350 rpm) had a 17.5% TCF rate (n = 14/80). Group F (0°/1350 rpm) had a 0% TCF rate (n = 0/80). Groups C and E had the highest TCF rates with a difference in TCF rates observed between the control group and Group C (p = .001) and between the control group and Group E (p < .001). CONCLUSION: Increased screw insertion angle and insertion speed appear to be predisposing factors for TCF development in cadaveric bone. CLINICAL SIGNIFICANCE: Ensuring screw insertion is coaxial with the pilot hole and using slower screw insertion speeds may help reduce the risk of TCF development.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

Favorable Neighborhood Walkability is Associated With Lower Burden of Cardiovascular Risk Factors Among Patients Within an Integrated Health System: The Houston Methodist Learning Health System Outpatient Registry.

This is the first study to investigate the relationship between neighborhood walkability and cardiovascular (CV) risk factors in the United States using a large population-based database. Cross-sectional study using data from 1.1 million patients over the age of 18 in the Houston Methodist Learning Health System Outpatient Registry (2016-2022). Using the 2019 WalkScore, patients were assigned to one of the 4 neighborhood walkability categories. The burden of CV risk factors (hypertension, diabetes, obesity, dyslipidemia, and smoking) was defined as poor, average, or optimal (>3, 1-2, 0 risk factors, respectively). We included 887,654 patients, of which 86% resided in the two least walkable neighborhoods. The prevalence of CV risk factors was significantly lower among participants in the most walkable neighborhoods irrespective of ASCVD status. After adjusting for age, sex, race/ethnicity, and socioeconomic factors, we found that adults living in the most walkable neighborhoods were more likely to have optimal CV risk profile than those in the least walkable ones (RRR 2.77, 95% CI 2.64-2.91). We observed an inverse association between neighborhood walkability and the burden of CV risk factors. These findings support multilevel health system stakeholder engagements and investments in walkable neighborhoods as a viable tool for mitigating the growing burden of modifiable CV risk factors.

Quadriceps Strain and TKA: Contribution of the Tourniquet and Intramedullary Rod to Postoperative Thigh Pain: A Randomized Controlled Trial.

BACKGROUND: Thigh pain is relatively common after total knee arthroplasty (TKA) and has been attributed to compression of the thigh muscles by the tourniquet used during surgery. Thigh pain that occurs after a TKA that was performed without a tourniquet may be due to a strain of the quadriceps muscle or insertion of the intramedullary (IM) rod. The purpose of the present study was to determine the cause of thigh pain after TKA in a randomized controlled trial evaluating tourniquet use, IM rod use, and quadriceps strain. METHODS: This prospective randomized controlled trial enrolled 97 subjects undergoing primary knee arthroplasty into 4 groups according to tourniquet use (yes or no) and IM rod use (yes or no). Quadriceps strain was evaluated with magnetic resonance imaging (MRI) on postoperative day 1 (POD 1). Data collected preoperatively, intraoperatively, and postoperatively until the 6-week clinical visit included pain levels for the knee and thigh (recorded separately) and knee range of motion. RESULTS: Regardless of tourniquet or IM rod use, 73 (75%) of the 97 patients reported thigh pain on POD 1. Thigh pain at 2 weeks postoperatively was indicative of a quadriceps strain. Use of a tourniquet and patient-reported thigh pain at 2 weeks increased the odds of a quadriceps strain, whereas IM rod use did not significantly contribute to thigh pain. CONCLUSIONS: The etiology of thigh pain after TKA may be multifactorial; however, an iatrogenic quadriceps strain is one source of thigh pain after TKA, especially if the pain persists 2 weeks after surgery. LEVEL OF EVIDENCE: Prognostic Level I . See Instructions for Authors for a complete description of levels of evidence.

Long-term outcome of dogs treated by surgical debridement of proximal humeral osteochondrosis.

OBJECTIVE: To evaluate long-term clinical outcomes of dogs surgically treated for proximal humeral osteochondrosis (OC). STUDY DESIGN: Cross-sectional study. SAMPLE POPULATION: Twenty dogs (n = 26 shoulders). METHODS: Dogs treated with surgical debridement of proximal humeral OC lesions >12 months prior were enrolled. Orthopedic examination (including limb circumference and shoulder goniometry), kinetic gait analysis, shoulder radiographs, shoulder computed tomography (CT), and shoulder arthroscopy were performed. All owners completed a dog mobility questionnaire. RESULTS: Brachial circumference (P = .003) and maximum shoulder extension (P = .013) were decreased and maximum shoulder flexion (P = .008) was increased (ie less flexion) in the OC limb versus the contralateral limb in unilaterally affected dogs. There were no differences in peak vertical force and vertical impulse between affected and unaffected limbs. Dogs demonstrated a 4.4% decrease in load distributed to the operated limb. Osteoarthritis was present in all shoulders treated for OC lesions. The degree of osteoarthritis in OC-affected shoulders was increased compared to the contralateral limb as evaluated on CT (P = .005) and radiography (P = .0001) in unilaterally affected cases. Moderate-to-severe synovitis was seen in all OC-affected joints. Arthroscopically, all lesions were noted to have patchy, incomplete cartilaginous infilling. Median of aggregate Liverpool Osteoarthritis in Dogs (LOAD) scores was 6. CONCLUSION: All dogs exhibited ipsilateral muscle atrophy and progressive osteoarthritis, with most dogs exhibiting subtle lameness on the subjective gait examination. Despite this, owner-perceived mobility was satisfactory. CLINICAL SIGNIFICANCE: Progression of joint disease over time should be expected; however, the abnormalities detected on examination appear to be of questionable clinical relevance.

Outcomes of novel 3D-printed fully porous titanium cup and a cemented highly cross-linked polyethylene liner in complex and revision total hip arthroplasty.

INTRODUCTION: A novel fully porous acetabular titanium shell has been designed to reduce stiffness mismatch between bone and implant and promote osseointegration in complex (cTHA) and revision total hip arthroplasty (rTHA). A highly cross-linked polyethylene (XLPE) liner is cemented within the cup to reduce wear rates and increase survivorship. This study reported the outcomes of an XLPE liner cemented into a novel 3D-printed fully porous cup in cTHA and rTHA. METHODS: Presented was a multicenter retrospective review of 40 patients (6 cTHA and 34 rTHA) who underwent THA with a fully porous titanium acetabular cup and cemented XLPE liner. Data were collected on demographics, surgical information, outcomes, including osseointegration and migration and implant survivorship. RESULTS: On average, patients were 71.42 ± 9.97 years old and obese (BMI: 30.36 ± 6.88 kg/m2) and were followed up for a mean time of 2.21 ± 0.77 years. Six patients underwent cTHA and 34 patients underwent rTHA. The mean hospital length of stay was 5.34 ± 3.34 days. Three (7.5%) 90-day readmissions were noted. Harris Hip Scores improved, on average, from 53.87 ± 12.58 preoperatively to 83.53 ± 12.15 postoperatively (P<0.001). One case of acetabular shell aspetic loosening with migration was noted. Thirty-nine of the 40 acetabular components were fully osseointegrated without migration. Two patients underwent re-revision surgery for PJI and one patient received acetabular shell+liner re-revision due to aseptic loosening. Kaplan-Meier analysis showed an all-cause revision-free survival rate of 95.0% at 6 months and 1 year, and 92.0% at 4-years. Aseptic acetabular cup, liner dislocation/loosening, and fracture-free survival was 100% at 6 months and 1-year, and 97.1% at 2 years. CONCLUSION: The combined use of a novel 3D-printed fully porous titanium acetabular shell and cemented XLPE acetabular liner yielded excellent rates of osseointegration, and all-cause and acetabular aseptic loosening survivorship at a minimum 1-year follow-up. Further long-term studies are needed to assess the longevity of this construct.

Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling.

The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads of Fusobacterium nucleatum correlate with shorter survival in patients. Here, we investigated the potential mechanisms underlying this association. We found that F. nucleatum infection induced both normal pancreatic epithelial cells and PDAC cells to secrete increased amounts of the cytokines GM-CSF, CXCL1, IL-8, and MIP-3α. These cytokines increased proliferation, migration, and invasive cell motility in both infected and noninfected PDAC cells but not in noncancerous pancreatic epithelial cells, suggesting autocrine and paracrine signaling to PDAC cells. This phenomenon occurred in response to Fusobacterium infection regardless of the strain and in the absence of immune and other stromal cells. Blocking GM-CSF signaling markedly limited proliferative gains after infection. Thus, F. nucleatum infection in the pancreas elicits cytokine secretion from both normal and cancerous cells that promotes phenotypes in PDAC cells associated with tumor progression. The findings support the importance of exploring host-microbe interactions in pancreatic cancer to guide future therapeutic interventions.

Black Line Sign in Focal Cortical Dysplasia IIB: A 7T MRI and Electroclinicopathologic Study.

BACKGROUND AND OBJECTIVES: We aim to provide detailed imaging-electroclinicopathologic characterization of the black line sign, a novel MRI marker for focal cortical dysplasia (FCD) IIB. METHODS: 7T T2*-weighted gradient-echo (T2*w-GRE) images were retrospectively reviewed in a consecutive cohort of patients with medically intractable epilepsy with pathology-proven FCD II, for the occurrence of the black line sign. We examined the overlap between the black line region and the seizure-onset zone (SOZ) defined by intracranial EEG (ICEEG) and additionally assessed whether complete inclusion of the black line region in the surgical resection was associated with postoperative seizure freedom. The histopathologic specimen was aligned with the MRI to investigate the pathologic underpinning of the black line sign. Region-of-interest-based quantitative MRI (qMRI) analysis on the 7T T1 map was performed in the black line region, entire lesional gray matter (GM), and contralateral/ipsilateral normal gray and white matter (WM). RESULTS: We included 20 patients with FCD II (14 IIB and 6 IIA). The black line sign was identified in 12/14 (85.7%) of FCD IIB and 0/6 of FCD IIA on 7T T2*w-GRE. The black line region was highly concordant with the ICEEG-defined SOZ (5/7 complete and 2/7 partial overlap). Seizure freedom was seen in 8/8 patients whose black line region was completely included in the surgical resection; in the 2 patients whose resection did not completely include the black line region, both had recurring seizures. Inclusion of the black line region in the surgical resection was significantly associated with seizure freedom (p = 0.02). QMRI analyses showed that the T1 mean value of the black line region was significantly different from the WM (p < 0.001), but similar to the GM. Well-matched histopathologic slices in one case revealed accumulated dysmorphic neurons and balloon cells in the black line region. DISCUSSION: The black line sign may serve as a noninvasive marker for FCD IIB. Both MRI-pathology and qMRI analyses suggest that the black line region was an abnormal GM component within the FCD. Being highly concordant with ICEEG-defined SOZ and significantly associated with seizure freedom when included in resection, the black line sign may contribute to the planning of ICEEG/surgery of patients with medically intractable epilepsy with FCD IIB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals with intractable focal epilepsy undergoing resection who have a 7T MRI with adequate image quality, the presence of the black line sign may suggest FCD IIB, be concordant with SOZ from ICEEG, and be associated with more seizure freedom if fully included in resection.

Mechanical evaluation of canine sacroiliac joint stabilization using two short screws.

OBJECTIVE: To assess the feasibility and mechanical stability of sacroiliac (SI) joint stabilization using 2 short 3.5 mm cortical screws, each spanning an average of 23% of the width of the sacral body. STUDY DESIGN: Cadaveric experimental study. SAMPLE POPULATION: Twenty-four canine pelvis specimens. METHODS: Pelvis specimens were prepared by disarticulation of the left SI joint and osteotomy of the left pubis and left ischium, and stabilized using a single long lag screw (LLS), 2 short lag screws (SLS) or 2 short positional screws (SPS). Computed tomography (CT) imaging was used to determine standardized screw lengths for each group and was repeated following implant insertion. Specimens were secured within a servohydraulic test frame and loaded through the acetabulum to simulate weight bearing under displacement control at 4 mm/min for 20 mm total displacement. Group mechanical testing data were compared. RESULTS: Peak load, yield load, and stiffness were more than 2 times greater in both the SLS and SPS groups when compared with the LLS group. No mechanical difference was identified between the short-screw groups. CONCLUSION: Sacroiliac luxation fixation using 2 short screws created a stronger, stiffer construct when compared with fixation using a single lag screw spanning 60% of the width of the sacral body. No mechanical advantage was observed between short screws inserted in positional vs. lag fashion. CLINICAL SIGNIFICANCE: Sacroiliac luxation fixation using 2 short screws creates a mechanically superior construct with a larger region of acceptable implant positioning and potentially reduced risk of iatrogenic injury compared with conventional fixation.

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Using magnetic resonance fingerprinting to characterize periventricular nodular heterotopias in pharmacoresistant epilepsy.

OBJECTIVE: We aimed to use a novel magnetic resonance fingerprinting (MRF) technique to examine in vivo tissue property characteristics of periventricular nodular heterotopia (PVNH). These characteristics were further correlated with stereotactic-electroencephalographic (SEEG) ictal onset findings. METHODS: We included five patients with PVNH who had SEEG-guided surgery and at least 1 year of seizure freedom or substantial seizure reduction. High-resolution MRF scans were acquired at 3 T, generating three-dimensional quantitative T1 and T2  maps. We assessed the differences between T1 and T2  values from the voxels in the nodules located in the SEEG-defined seizure onset zone (SOZ) and non-SOZ, on -individual and group levels. Receiver operating characteristic analyses were performed to obtain the optimal classification performance. Quantification of SEEG ictal onset signals from the nodules was performed by calculating power spectrum density (PSD). The association between PSD and T1 /T2  values was further assessed at different frequency bands. RESULTS: Individual-level analysis showed T1 was significantly higher in SOZ voxels than non-SOZ voxels (p < .05), with an average 73% classification accuracy. Group-level analysis also showed higher T1 was significantly associated with SOZ voxels (p < .001). At the optimal cutoff (normalized T1 of 1.1), a 76% accuracy for classifying SOZ nodules from non-SOZ nodules was achieved. T1  values were significantly associated with ictal onset PSD at the ultraslow, θ, ß, γ, and ripple bands (p < .05). T2  values were significantly associated with PSD only at the ultraslow band (p < .05). SIGNIFICANCE: Quantitative MRF measures, especially T1 , can provide additional noninvasive information to separate nodules in SOZ and non-SOZ. The T1 and T2 tissue property changes carry electrophysiological underpinnings relevant to the epilepsy, as shown by their significant positive associations with power changes during the SEEG seizure onset. The use of MRF as a supplementary noninvasive tool may improve presurgical evaluation for patients with PVNH and pharmacoresistant epilepsy.

Pancreatic head vs pancreatic body/tail cancer: Are they different?

BACKGROUND: The impact of pancreatic tumor location on patient survival has been studied in large national data-based analyses which yielded controversial results. AIM: To explore if pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have different overall survival (OS), molecular signature and response to chemotherapy. METHODS: We retrospectively queried patient records from July 2016 to June 2020 in our institution. Patient demographics, cancer stage on diagnosis, tumor location, somatic mutations, treatment, and survival are recorded and analyzed. A test is considered statistically significant if the P value was < 0.05. RESULTS: We reviewed 101 patients with complete records, among which 67 (66.34%) were PHC and 34 (33.66%) were PBTC. More PHC were diagnosed at younger age [61.49 vs 68.97, P = 0.010], earlier stages (P = 0.006) and underwent surgical resection (P = 0.025). There were no significant differences among all mutations and pathways studied except for TP53 mutations (37.0% in PHC vs 70.0% in PBTC, P = 0.03). OS was not statistically different between PHC and PBTC (P = 0.636) in the overall population and in subgroups according to surgical resection status or stages. In terms of response to chemotherapy, chemotherapy regimens (FOLFIRINOX-based vs gemcitabine-based) didn't impact disease free interval in those who had surgical resection in either PHC (P = 0.546) or PBTC (P = 0.654), or the duration of response to first line palliative treatment in those with advanced disease in PHC (P = 0.915) or PBTC (P = 0.524). CONCLUSION: Even though PHC and PBTC have similar poor OS and response to chemotherapy, the different presentations and molecular profiles indicate they are different diseases. Utilization of molecular profiling to develop targeted therapy for individualization of treatment is needed.

Partial penile amputation using a thoracoabdominal stapler in nine dogs.

OBJECTIVES: To describe a novel technique for partial anatomic penile amputation using a thoracoabdominal stapler in dogs and to report any associated short-term peri-operative complications and clinical outcomes associated with the procedure. MATERIALS AND METHODS: Medical records from a tertiary referral hospital were reviewed for dogs undergoing penile amputation and scrotal urethrostomy between October 2007 and December 2019. Data collected included patient signalment, clinical signs on presentation, indication for penile amputation, surgical technique, duration of surgery, post-operative complications, and short-term outcome. RESULTS: Nine dogs were included in the study. Indications for surgery were for treatment of chronic paraphimosis and priapism (n = 3), recurrent urethral prolapse (n = 2), balanoposthitis (n = 1), masses arising from the penis, prepuce, and/or urethra (n = 2), and penile trauma (n = 1). All dogs underwent a scrotal urethrostomy followed by a partial penile amputation with a thoracoabdominal stapler. All dogs suffered mild post-operative haemorrhage from the urethrostomy stoma. On recovery from general anaesthesia, 2/9 dogs were painful and another 2/9 dogs were dysphoric. Two dogs experienced incisional complications with mild swelling around the urethrostomy stoma. One dog experienced an infection of the penile amputation site 21 days after surgery. The short-term outcomes for this procedure were excellent in 8/9 dogs. These outcomes were based on owner assessment of comfort and monitoring throughout the recovery period, manual palpation of the surgical site at the time re-evaluation, and surgeon visualization of successful voluntary urination 14-35 days after surgery. CLINICAL SIGNIFICANCE: Use of a thoracoabdominal stapler is effective in achieving partial anatomic penile amputation in dogs.