Efficacy, Safety and Acceptability of a Very-Low-Energy Diet in Adolescents with Obesity: A Fast Track to Health Sub-Study.

The aim of this study was to determine the efficacy, safety and acceptability of a 4-week very-low-energy diet (VLED) program for adolescents with obesity. Adolescents (13-17 years) with obesity and ≥1 obesity-related complication were Fast Track to Health 52-week randomized controlled trial participants. Adolescents undertook a 4-week micronutrient-complete VLED (800 kcal/day), with weekly dietitian support. Anthropometric data were recorded at baseline and week-4 and side-effects at day 3-4, week-1, -2, -3 and -4. Adolescents completed an acceptability survey at week-4. A total of 134 adolescents (14.9 ± 1.2 years, 50% male) had a 5.5 ± 2.9 kg (p < 0.001) mean weight loss at week-4: 95% experienced ≥1 and 70% experienced ≥3 side-effects during the VLED program, especially during the first week. Hunger, fatigue, headache, irritability, loose stools, constipation and nausea were most common. Reporting more side-effects at day 3-4 correlated with greater weight loss at week-4 (r = -0.188, p = 0.03). Adolescents reported 'losing weight' (34%) and 'prescriptive structure' (28%) as the most positive aspects of VLED, while 'restrictive nature' (45%) and 'meal replacement taste' (20%) were least liked. A dietitian-monitored short-term VLED can be implemented safely and is acceptable for many adolescents seeking weight loss, despite frequent side-effects. Investigating predictors of acceptability and effectiveness could determine adolescents most suited to VLED programs.

Hepatocellular Adenoma Update: Diagnosis, molecular Classification, and Clinical Course.

Hepatocellular adenomas (HCA) are acquired focal liver lesions, usually 3-5 cm, that occur mainly in young-to-middle-aged women who are on long-term estrogen-containing contraceptives or young men after prolonged use of anabolic steroids. Furthermore, distinct underlying diseases, such as obesity, Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), glycogen storage disease, etc are considered risk factors. Adenomatosis is when ≥ 10 adenomas occur simultaneously. Histologically, HCAs consist of hepatocytes arranged in strands without bile ducts or portal veins and are supplied only arterially. The 2017 Bordeaux classification, in particular Nault et al., divided HCAs into eight subtypes according to their pheno- and genotypic characteristics. This includes HCAs with hepatocyte-nuclear-factor (HNF1-alpha mutation), HCAs with ß-catenin mutation, and HCAs without either of these genetic mutations, which are further subdivided into HCAs with and without inflammatory cells.[1] HCAs should no longer be classified as purely benign without histologic workup since three of the eight subtypes are considered high-risk lesions, requiring adequate management: malignant transformation of the pure (ßex3-HCA) and mixed inflammatory/ß-catenin exon 3 (ßex3-IHCA) adenomas, as well as potential bleeding of the sonic hedgehog HCA (sh-HCA) and pure (ßex7/8-HCA) and mixed inflammatory/ß-catenin exon 7/8 (ßex7/8-IHCA). Elective surgery is recommended for any HCA in a male, or for any HCA exceeding 5 cm. Although MRI can classify up to 80% of adenomas, if findings are equivocal, biopsy remains the reference standard for adenoma subtype.

Intermittent Energy Restriction for Adolescents With Obesity: The Fast Track to Health Randomized Clinical Trial.

Importance: Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management. Objective: To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity. Design, Setting, and Participants: This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included. Interventions: Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52). Main Outcomes and Measures: The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed. Results: A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups. Conclusions and Relevance: These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice. Trial Registration: http://anzctr.org.au Identifier: ACTRN12617001630303.

Symptoms of Depression, Eating Disorders, and Binge Eating in Adolescents With Obesity: The Fast Track to Health Randomized Clinical Trial.

Importance: Depression and eating disorders are heightened for adolescents with obesity. Clinical reviews alongside self-report questionnaires are important to ensure appropriate intervention. Objective: To evaluate changes in self-report symptoms of depression, eating disorders, and binge eating in adolescents with obesity during the Fast Track to Health trial. Design, Setting, and Participants: This was a randomized clinical trial conducted from 2018 to 2023. It was a multisite trial conducted at children's hospitals in Sydney, New South Wales, and Melbourne, Victoria, Australia, and included adolescents (13-17 years) with obesity (defined as adult equivalent body mass index ≥30; calculated as weight in kilograms divided by height in meters squared) and 1 or more related complications. Interventions: Duration was 52 weeks including a very low energy diet for 4 weeks followed by intermittent energy restriction (IER) or continuous energy restriction (CER). Main Outcomes and Measures: Self-report symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised 10-Item Version for Adolescents [CESDR-10]; scores 0-30), eating disorders (Eating Disorder Examination Questionnaire [EDE-Q]; scores 0-6), and binge eating (Binge Eating Scale [BES]; scores 0-46) were assessed. Adolescents were screened for depression and eating disorders (weeks 0, 4, 16, and 52) and monitored for the onset of new symptoms of disordered eating during dietetic consults. Results: Of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) enrolled, median baseline EDE-Q score was 2.28 (IQR, 1.43-3.14), median baseline CESDR-10 score was 9.00 (IQR, 4.00-14.50), and median baseline BES score was 11.00 (IQR, 5.00-17.00). There were no differences between groups for change in CESDR-10 (mean difference at week 52, 0.75; 95% CI, -1.86 to 3.37), EDE-Q (mean difference at week 52, 0.02; 95% CI, -0.41 to 0.45), or BES (mean difference at week 52, -2.91; 95% CI, -5.87 to 0.05). The within-group reductions at week 4 were maintained at week 52, for CESDR-10 and EDE-Q, indicating reduced symptoms of depression and eating disorders. Within-group reductions on the BES were maintained in the IER group only. Seventeen adolescents (12.1%) required support or referral for depression and/or disordered eating, including 7 (5%; 5 IER, 2 CER) adolescents who experienced the onset or reemergence of symptoms during the intervention. Conclusions and Relevance: Results suggest that many treatment-seeking adolescents with obesity self-reported symptoms of depression and eating disorders. Although symptoms reduced for most, some required additional support. Obesity treatment is an opportune time to screen and monitor for depression and disordered eating. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001630303.

Identifying Predictor Variables for a Composite Risk Prediction Tool for Gestational Diabetes and Hypertensive Disorders of Pregnancy: A Modified Delphi Study.

A composite cardiometabolic risk prediction tool will support the systematic identification of women at increased cardiometabolic risk during pregnancy to enable early screening and intervention. This study aims to identify and select predictor variables for a composite risk prediction tool for cardiometabolic risk (gestational diabetes mellitus and/or hypertensive disorders of pregnancy) for use in the first trimester. A two-round modified online Delphi study was undertaken. A prior systematic literature review generated fifteen potential predictor variables for inclusion in the tool. Multidisciplinary experts (n = 31) rated the clinical importance of variables in an online survey and nominated additional variables for consideration (Round One). An online meeting (n = 14) was held to deliberate the importance, feasibility and acceptability of collecting variables in early pregnancy. Consensus was reached in a second online survey (Round Two). Overall, 24 variables were considered; 9 were eliminated, and 15 were selected for inclusion in the tool. The final 15 predictor variables related to maternal demographics (age, ethnicity/race), pre-pregnancy history (body mass index, height, history of chronic kidney disease/polycystic ovarian syndrome, family history of diabetes, pre-existing diabetes/hypertension), obstetric history (parity, history of macrosomia/pre-eclampsia/gestational diabetes mellitus), biochemical measures (blood glucose levels), hemodynamic measures (systolic blood pressure). Variables will inform the development of a cardiometabolic risk prediction tool in subsequent research. Evidence-based, clinically relevant and routinely collected variables were selected for a composite cardiometabolic risk prediction tool for early pregnancy.

Disease severity prognostication in primary sclerosing cholangitis: a validation of the Anali scores and comparison with the potential functional stricture.

OBJECTIVES: Our aim was twofold. First, to validate Anali scores with and without gadolinium (ANALIGd and ANALINoGd) in primary sclerosing cholangitis (PSC) patients. Second, to compare the ANALIs prognostic ability with the recently-proposed potential functional stricture (PFS). MATERIALS AND METHODS: This retrospective study included 123 patients with a mean age of 41.5 years, who underwent gadoxetic acid-enahnced MRI (GA-MRI). Five readers independently evaluated all images for calculation of ANALIGd and ANALINoGd scores based upon following criteria: intrahepatic bile duct change severity, hepatic dysmorphia, liver parenchymal heterogeneity, and portal hypertension. In addition, hepatobiliary contrast excretion into first-order bile ducts was evaluated on 20-minute hepatobiliary-phase (HBP) images to assess PFS. Inter- and intrareader agreement were calculated (Fleiss´and Cohen kappas). Kaplan-Meier curves were generated for survival analysis. ANALINoGd, ANALIGd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis). RESULTS: Inter-reader agreement was almost perfect (Ï° = 0.81) for PFS, but only moderate-(Ï° = 0.55) for binary ANALINoGd. For binary ANALIGd, the agreement was slightly better on HBP (Ï° = 0.64) than on arterial-phase (AP) (Ï° = 0.53). Univariate Cox regression showed that outcomes for decompensated cirrhosis, orthotopic liver transplantation or death significantly correlated with PFS (HR (hazard ratio) = 3.15, p < 0.001), ANALINoGd (HR = 6.42, p < 0.001), ANALIGdHBP (HR = 3.66, p < 0.001) and ANALIGdAP (HR = 3.79, p < 0.001). Multivariate analysis identified the PFS, all three ANALI scores, and Revised Mayo Risk Score as independent risk factors for outcomes (HR 3.12, p < 0.001; 6.12, p < 0.001; 3.56, p < 0.001;3.59, p < 0.001; and 4.13, p < 0.001, respectively). CONCLUSION: ANALINoGd and GA-MRI-derived ANALI scores and PFS could noninvasively predict outcomes in PSC patients. CLINICAL RELEVANCE STATEMENT: The combined use of Anali scores and the potential functional stricture (PFS), both derived from unenhanced-, and gadoxetic acid enhanced-MRI, could be applied as a diagnostic and prognostic imaging surrogate for counselling and monitoring primary sclerosing cholangitis patients. KEY POINTS: Primary sclerosing cholangitis patients require radiological monitoring to assess disease stability and for the presence and type of complications. A contrast-enhanced MRI algorithm based on potential functional stricture and ANALI scores risk-stratified these patients. Unenhanced ANALI score had a high negative predictive value, indicating some primary sclerosing cholangitis patients can undergo non-contrast MRI surveillance.

Bridging the Evidence and Practice Gap in Chronic Kidney Disease: A System Thinking Approach to Population Health.

Chronic kidney disease (CKD) is common, costly, and life-limiting, requiring dialysis and transplantation in advanced stages. Although effective guideline-based therapy exists, the asymptomatic nature of CKD together with low health literacy, adverse social determinants of health, unmet behavioral health needs, and primary care providers' (PCP) limited understanding of CKD result in defects in screening and diagnosis. Care is fragmented between PCPs and specialty nephrologists, with limited time, expertise, and resources to address systemic gaps. In this article, the authors define how they classified defects in care and report the current numbers of patients exposed to these defects, both nationally and in their health system Accountable Care Organization. They describe use of the health system's three-pillar leadership model (believing, belonging, and building) to empower providers to transform CKD care. Believing entailed engaging individuals to believe defects in CKD care could be eliminated and were a collective responsibility. Belonging fostered the creation of learning communities that broke down silos and encouraged open communication and collaboration between PCPs and nephrologists. Building involved constructing a fractal management infrastructure with transparent reporting and shared accountability, which would enable success in innovation and transformation. The result is proactive and relational CKD care organized around the patient's needs in University Hospitals Systems of Excellence. Systems of excellence combine multiple domains of expertise to promote best practice guidelines and integrate care throughout the system. The authors further describe a preliminary pilot of the CKD System of Excellence in primary care.

[Path to health insurance coverage - The Clearing Center 1.0 at the Public Health Authority in Frankfurt am Main]. / Wege in den Krankenversicherungsschutz ­ Das Pilotprojekt Clearingstelle 1.0 am Gesundheitsamt Frankfurt am Main.

Nationwide, an estimated 500,000 to 1 million people are not insured and therefore lack access to regular health structures, which can have fatal consequences for the health of those affected. Especially in large cities, there are low-threshold medical outpatient clinics that offer basic health care parallel to the regular system. Sustainable solutions for ensuring adequate healthcare are lacking. Clearing centers (German: Clearingstelle), serving as contact points for people without health insurance coverage, and the concept of an Anonymous Treatment Voucher (German: Anonymer Behandlungsschein; ABS), bridge the gap between parallel and regular health systems. With the pilot implementation of "Clearing Center 1.0" at the Public Health Authority in Frankfurt am Main from 2020 to 2022, the basic medical care of Humanitarian Consultation Hour was complemented by professional social counseling with the aim of referring as many individuals as possible to the statutory regular system. The expansion of the counseling services and the permanent establishment of the clearing center in Frankfurt am Main are declared goals for the Public Health Authority.

Intervention Strategies to Address Barriers and Facilitators to a Healthy Lifestyle Using the Behaviour Change Wheel: A Qualitative Analysis of the Perspectives of Postpartum Women.

Postpartum women experience unique barriers to maintaining healthy lifestyles after birth. Theory-based behaviour change techniques and intervention strategies can be integrated into postpartum lifestyle interventions to enable women to overcome barriers to change. This study aims to explore barriers and facilitators to engaging in healthy postpartum lifestyle behaviours and develop intervention strategies for integration in a postpartum lifestyle intervention using the Behaviour Change Wheel (BCW). Semi-structured interviews were conducted with women up to two years postpartum (n = 21). Interviews were thematically analysed, themes were mapped to the Capability, Opportunity, and Motivation Model of Behaviour Change and intervention strategies were developed using the BCW. Findings suggest that women face barriers and facilitators within capability (sleep deprivation, mental exhaustion, ability to plan), opportunity (support of friends, partners and extended families) and motivation (challenges with prioritising self, exercise to cope with stress). Intervention strategies included supporting behaviour regulation and sleep to enhance capability, engaging partners, strengthening peer support to create opportunities and highlighting the mental health benefits of healthy lifestyles to inspire motivation. Integrating targeted evidence-based behaviour change strategies into postpartum lifestyle interventions may support women in overcoming commonly reported barriers to a healthy lifestyle.

Conspecific and heterospecific cueing in shelter choices of Blaptica dubia cockroaches.

Background: Like many cockroaches, Argentinian wood roaches, Blaptica dubia, prefer darker shelters over lighter shelters. In three experiments, we asked whether chemical cues from other roaches might influence shelter choice, a process known as conspecific or heterospecific cueing, depending on whether the cues come from an individual of the same or a different species, respectively. Methods: Each experiment involved trials with focal B. dubia cockroaches in testing arenas containing plastic shelters of varying levels of darkness, with filter paper under each shelter acting as a carrier for chemical cues. In Experiment 1, we tested female and male B. dubia cockroaches with two shelters matched for darkness but differing in cues (conspecific vs. none). The shelter with no cue contained a blank filter paper as a control. In Experiment 2 (conspecific cueing) and Experiment 3 (heterospecific cueing), we tested B. dubia cockroach choices for lighter or darker shelters with filter papers containing chemical cues of other roaches or no chemical cues. For the conspecific cueing study of Experiment 2, we used chemical cues from other B. dubia cockroaches. In contrast, for the heterospecific cueing study of Experiment 3, we used chemical cues from a different species, the death's head cockroach, Blaberus craniifer. Results: In Experiment 1, B. dubia cockroaches overwhelmingly preferred shelters with conspecific chemical cues over darkness-matched shelters without cues. In Experiments 2 and 3, they strongly preferred darker shelters, especially when chemical cues were present. Additionally, they were more likely to be under the lighter shelter when chemical cues were present there. These results reveal that the public information B. dubia cockroaches gain from chemical cues-including those from other species-can drive shelter choices in this species.

Are dilution, slow injection and care bolus technique the causal solution to mitigating arterial-phase artifacts on gadoxetic acid-enhanced MRI? A large-cohort study.

OBJECTIVE: Arterial-phase artifacts are gadoxetic acid (GA)-enhanced MRI's major drawback, ranging from 5 to 39%. We evaluate the effect of dilution and slow injection of GA using automated fluoroscopic triggering on liver MRI arterial-phase (AP) acquisition timing, artifact frequency, and lesion visibility. METHODS AND MATERIALS: Saline-diluted 1:1 GA was injected at 1 ml/s into 1413 patients for 3 T liver MRI. Initially, one senior abdominal radiologist, i.e., principal investigator (PI), assessed all MR exams and compared them to previous and follow-up images, as well as the radiology report on record, determining the standard of reference for lesion detection and characterization. Then, three other readers independently evaluated the AP images for artifact type (truncation (TA), transient severe motion (TSM) or mixed), artifact severity (on a 5-point scale), acquisition timing (on a 4-point scale) and visibility (on a 5-point scale) of hypervascular lesions ≥ 5 mm, selected by the PI. Artifact score ≥ 4 and artifact score ≤ 3 were considered significant and non-significant artifacts, respectively. RESULTS: Of the 1413 exams, diagnostic-quality arterial-phase images included 1100 (77.8%) without artifacts, 220 (15.6%) with minimal, and 77 (5.4%) with moderate artifacts. Only 16 exams (1.1%) had significant artifacts, 13 (0.9%) with severe artifacts (score 4), and three (0.2%) non-diagnostic artifacts (score 5). AP acquisition timing was optimal in 1369 (96.8%) exams. Of the 449 AP hypervascular lesions, 432 (96.2%) were detected. CONCLUSION: Combined dilution and slow injection of GA with MR results in well-timed arterial-phase images in 96.8% and a reduction of exams with significant artifacts to 1.1%. CLINICAL RELEVANCE STATEMENT: Hypervascular lesions, in particular HCC detection, hinge on arterial-phase hyperenhancement, making well-timed, artifact-free arterial-phase images a prerequisite for accurate diagnosis. Saline dilution 1:1, slow injection (1 ml/s), and automated bolus triggering reduce artifacts and optimize acquisition timing. KEY POINTS: • There was substantial agreement among the three readers regarding the presence and type of arterial-phase (AP) artifacts, acquisition timing, and lesion visibility. • Impaired AP hypervascular lesion visibility occurred in 17 (3.8%) cases; in eight lesions due to mistiming and in nine lesions due to significant artifacts. • When AP timing was suboptimal, it was too late in 40 exams (3%) and too early in 4 exams (0.2%) of exams.

Modified Lemaire Lateral Extra-Articular Tenodesis Using an Inlay Technique and All-Suture Knotless Anchor Fixation.

Appreciation of persistent anterolateral rotatory instability and graft failure after anterior cruciate ligament (ACL) reconstruction procedures has led surgeons to adopt the addition of lateral extra-articular tenodesis (LET) in both the revision and primary setting. Multiple techniques have been shown to eliminate anterolateral rotatory instability and reduce forces on the ACL graft, which has translated to lower re-rupture rates and improved patient outcomes. The risk of ACL/LET tunnel convergence can potentially compromise the fixation of one or both graft reconstructions. This article describes a technique for LET fixation which minimizes the depth of the LET femoral bone socket and utilizes low-profile implants thus mitigating this risk.

Refractory shoulder injury related to vaccine administration: correlation with culture presence of Cutibacterium acnes.

Background: Shoulder pain following intramuscular administration of vaccine is common. However, a small number of patients experience prolonged pain and dysfunction atypical to normal transient postvaccination shoulder pain. Shoulder Injury Related to Vaccine Administration (SIRVA) remains incompletely understood, whether a robust immune response to vaccine antigen or inappropriate injection technique with needle placement in synovial or bursal tissue, or some combination of the two. Symptoms overlap with those of Cutibacterium acnes (C. acnes) infection but the relationship between the two, if any, has not been evaluated. Methods: Clinical case files were reviewed for 3 cases of SIRVA with positive cultures for C. acnes were reviewed. Presentation, treatment, and clinical outcomes were compared. Results: In all cases, patients were thin (body mass index < 23), females, who had high injection placement of a vaccine, all patients had positive magnetic resonance imaging findings of increased signal in the subacromial bursa, and/or greater tuberosity. All patients underwent arthroscopic débridement and culture harvest and cultures were positive for C. acnes. A combination of oral and intravenous antibiotics was used, and all patients demonstrated clinical improvement from the preoperative state. Discussion: This case series presents 3 patients with refractory SIRVA who ultimately underwent arthroscopic irrigation and débridement with culture biopsy. Each case had culture results positive for C. acnes and all responded, at least partially, to arthroscopic débridement and intravenous antibiotic therapy. The purpose of this manuscript is to raise awareness of potential coexistence of SIRVA and C. acnes which may be of assistance to surgeons treating refractory cases of SIRVA.

Diagnosis of functional strictures in patients with primary sclerosing cholangitis using hepatobiliary contrast-enhanced MRI: a proof-of-concept study.

OBJECTIVES: PSC strictures are routinely diagnosed on T2-MRCP as dominant- (DS) or high-grade stricture (HGS). However, high inter-observer variability limits their utility. We introduce the "potential functional stricture" (PFS) on T1-weighted hepatobiliary-phase images of gadoxetic acid-enhanced MR cholangiography (T1-MRC) to assess inter-reader agreement on diagnosis, location, and prognostic value of PFS on T1-MRC vs. DS or HGS on T2-MRCP in PSC patients, using ERCP as the gold standard. METHODS: Six blinded readers independently reviewed 129 MRIs to diagnose and locate stricture, if present. DS/HGS was determined on T2-MRCP. On T1-MRC, PFS was diagnosed if no GA excretion was seen in the CBD, hilum or distal RHD, or LHD. If excretion was normal, "no functional stricture" (NFS) was diagnosed. T1-MRC diagnoses (NFS = 87; PFS = 42) were correlated with ERCP, clinical scores, labs, splenic volume, and clinical events. Statistical analyses included Kaplan-Meier curves and Cox regression. RESULTS: Interobserver agreement was almost perfect for NFS vs. PFS diagnosis, but fair to moderate for DS and HGS. Forty-four ERCPs in 129 patients (34.1%) were performed, 39 in PFS (92.9%), and, due to clinical suspicion, five in NFS (5.7%) patients. PFS and NFS diagnoses had 100% PPV and 100% NPV, respectively. Labs and clinical scores were significantly worse for PFS vs. NFS. PFS patients underwent more diagnostic and therapeutic ERCPs, experienced more clinical events, and reached significantly more endpoints (p < 0.001) than those with NFS. Multivariate analysis identified PFS as an independent risk factor for liver-related events. CONCLUSION: T1-MRC was superior to T2-MRCP for stricture diagnosis, stricture location, and prognostication. CLINICAL RELEVANCE STATEMENT: Because half of PSC patients will develop clinically-relevant strictures over the course of the disease, earlier more confident diagnosis and correct localization of functional stricture on gadoxetic acid-enhanced MRI may optimize management and improve prognostication. KEY POINTS: • There is no consensus regarding biliary stricture imaging features in PSC that have clinical relevance. • Twenty-minute T1-weighted MRC images correctly classified PSC patients with potential (PFS) vs with no functional stricture (NFS). • T1-MRC diagnoses may reduce the burden of diagnostic ERCPs.

Correlation of histologic, imaging, and artificial intelligence features in NAFLD patients, derived from Gd-EOB-DTPA-enhanced MRI: a proof-of-concept study.

OBJECTIVE: To compare unsupervised deep clustering (UDC) to fat fraction (FF) and relative liver enhancement (RLE) on Gd-EOB-DTPA-enhanced MRI to distinguish simple steatosis from non-alcoholic steatohepatitis (NASH), using histology as the gold standard. MATERIALS AND METHODS: A derivation group of 46 non-alcoholic fatty liver disease (NAFLD) patients underwent 3-T MRI. Histology assessed steatosis, inflammation, ballooning, and fibrosis. UDC was trained to group different texture patterns from MR data into 10 distinct clusters per sequence on unenhanced T1- and Gd-EOB-DTPA-enhanced T1-weighted hepatobiliary phase (T1-Gd-EOB-DTPA-HBP), then on T1 in- and opposed-phase images. RLE and FF were quantified on identical sequences. Differences of these parameters between NASH and simple steatosis were evaluated with χ2- and t-tests, respectively. Linear regression and Random Forest classifier were performed to identify associations between histological NAFLD features, RLE, FF, and UDC patterns, and then determine predictors able to distinguish simple steatosis from NASH. ROC curves assessed diagnostic performance of UDC, RLE, and FF. Finally, we tested these parameters on 30 validation cohorts. RESULTS: For the derivation group, UDC-derived features from unenhanced and T1-Gd-EOB-DTPA-HBP, plus from T1 in- and opposed-phase, distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.02, respectively) with 85% and 80% accuracy, respectively, while RLE and FF distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.004, respectively), with 83% and 78% accuracy, respectively. On multivariate regression analysis, RLE and FF correlated only with fibrosis (p = 0.040) and steatosis (p ≤ 0.001), respectively. Conversely, UDC features, using Random Forest classifier predictors, correlated with all histologic NAFLD components. The validation group confirmed these results for both approaches. CONCLUSION: UDC, RLE, and FF could independently separate NASH from simple steatosis. UDC may predict all histologic NAFLD components. CLINICAL RELEVANCE STATEMENT: Using gadoxetic acid-enhanced MR, fat fraction (FF > 5%) can diagnose NAFLD, and relative liver enhancement can distinguish NASH from simple steatosis. Adding AI may let us non-invasively estimate the histologic components, i.e., fat, ballooning, inflammation, and fibrosis, the latter the main prognosticator. KEY POINTS: • Unsupervised deep clustering (UDC) and MR-based parameters (FF and RLE) could independently distinguish simple steatosis from NASH in the derivation group. • On multivariate analysis, RLE could predict only fibrosis, and FF could predict only steatosis; however, UDC could predict all histologic NAFLD components in the derivation group. • The validation cohort confirmed the findings for the derivation group.

Deciphering the Hermeticae Philosophiae Medulla: Textual Cultures of Alchemical Secrecy.

This article presents the decryption, historical analysis, and alchemical interpretation of an alchemical cipher found in a shared notebook of John and Arthur Dee (British Library MS Sloane 1902). The cipher is an early example of a Bellaso/Della Porta/Vigenère type, a strong encryption method which was historically deemed indecipherable. The essay explores the medical and alchemical context for the manuscript into which the cipher was copied and provides the transcription, plaintext solution (in Latin), and English translation of the encrypted text. Further, it interprets the enciphered text through the lens of alchemical practice and provides evidence for the dissemination of this cipher as part of a larger alchemical knowledge network.

Participant recruitment for paediatric research using social media: A practical 'how-to' guide for researchers.

AIM: Social media platforms are being increasingly used to support participant recruitment into paediatric health-related research. This study aimed to develop a multi-phase approach for using social media as a recruitment strategy for paediatric research studies. METHODS: The process was informed by the authors' prior experiences recruiting for paediatric obesity-related research studies, expertise in social media marketing and digital participant/ patient recruitment. Reflection on these experiences resulted in the iterative creation of a draft process which was further refined. A narrative literature review using a structured search was conducted to refine and augment the content and finalise the process. RESULTS: A six-phase recruitment approach was developed that includes: (i) plan for social media use as a recruitment strategy, (ii) explore relevant ethical considerations to protect the wellbeing of potentially vulnerable groups and create an ethical management plan, (iii) identify and understand the different target audiences and develop the advertising strategy, (iv) develop and design campaign content, (v) implement, monitor and iteratively refine the recruitment campaign, (vi) evaluate the campaign success. Potential activities and key considerations relevant for paediatric research are presented within each phase. CONCLUSION: Due to the widespread use and diverse characteristics of social media users, social media has the potential to disseminate details of research opportunities to community members who may otherwise not hear about, engage with, and potentially benefit from research participation. Researchers should collaborate with communication experts and target audiences to generate relevant and effective recruitment campaigns. Researchers should implement processes to protect vulnerable audiences' wellbeing at each stage of the process. Recruitment via social media may support wider community participation in research studies designed to improve young people's health.

Harvest of All-Soft Tissue Quadriceps Tendon Autograft for Anterior Cruciate Ligament Reconstruction With or Without Closure of Resulting Defect Has No Effect on Patellar Height.

Purpose: To evaluate the radiographic effect of quadriceps tendon harvest on patellar height and to determine whether closure of a quadriceps graft harvest defect resulted in a significant change in patellar height compared to nonclosure. Methods: We conducted a retrospective review of prospectively enrolled patients. The institutional database was queried and all patients who underwent quadriceps autograft anterior cruciate ligament reconstruction between 2015 and March 2020 were included. Graft harvest length in millimeters and final graft diameter after preparation for implantation were obtained from the operative record and demographic data were obtained from the medical record. Radiographic analysis was performed of eligible patients using standard ratios of patellar height: Insall-Salvati (IS), Blackburn-Peele (BP), and Caton-Deschamps (CD). Measurements were performed using digital calipers on a digital imaging system by 2 postgraduate fellow surgeons. Preoperative and postoperative radiographs were performed at 0° according to a standard protocol. Postoperative radiographs were performed 6 weeks postoperatively in all cases. Preoperative patellar height ratios were compared with postoperative patellar height ratios for all patients using t-tests. Subanalysis was then performed to compare the effect of closure of with nonclosure on patellar height ratios using repeated-measures analysis of variance. Interrater reliability between the 2 reviewers was assessed using an intraclass correlation coefficient calculation. Results: In total, 70 patients met final inclusion criteria. There were no statistically significant changes from pre- to postoperative values for either reviewer for IS (reviewer 1, P = .47; reviewer 2, P = .353), BP (reviewer 1, P = .98; reviewer 2, P = .907), or CD (reviewer 1, P = .107; reviewer, 2 P = .188). The closure and nonclosure groups were adequately powered and no statistically significant demographic differences between the closure and nonclosure groups was identified for sex (P = .066), age (P = .343), weight (P = .881), height (P = .42), laterality (P = 1), meniscal repair (P = .332), graft diameter (P = .068), or graft length (P = .183). According to the repeated measures analysis of variance, closure of the quadriceps defect had no significant impact on any of the knee ratios. However, reviewer identity had a significant influence on the CD ratio. Intraclass correlation coefficient analysis revealed excellent agreement between reviewers for the IS (0.982) and BP (0.954) ratios, but only moderate-to-good agreement for the CD (0.751) ratio. Conclusions: Harvest of quadriceps tendon graft does not result in radiographic changes in patellar height. Furthermore, closure of the quadriceps defect does not appear to result in radiographic changes in patellar height. Level of Evidence: III, retrospective comparative trial.