High Variability in Standardized Outcome Thresholds of Clinically Important Changes in Shoulder Instability Surgery: A Systematic Review.

PURPOSE: The purpose of this study was to examine reported MCID and PASS values for PROMs following shoulder instability surgery and assess variability in published values depending on the surgery performed. Secondarily, our aims were to describe the methods used to derive MCID and PASS values in the published literature, including anchor-based, distribution-based, or other approaches, and to assess the frequency of MCID and PASS usage in studies on shoulder instability surgery. METHODS: A systematic review of MCID and PASS values following Bankart, Latarjet, and Remplissage procedures was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The Embase, Pubmed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were queried from 1985 to 2023. Inclusion criteria included studies written in English, and studies reporting utilization MCID or PASS for patient reported outcome measures (PROMS) following Latarjet, Bankart, Remplissage approaches for shoulder instability surgery. Extracted data included study population characteristics, intervention characteristics, and outcomes of interest. Continuous data were described using median and range. Categorical variables, including PROMs reported and MCID/PASS methods, were described using percentages. As MCID is a patient-level metric and not a group-level metric, the authors validated that all included studies reported proportions (%) of subjects that met or exceeded the MCID. RESULTS: A total of 174 records were screened, and 8 studies were included in this review. MCID was the most widely utilized outcome threshold which was reported in all 8 studies, with only 2 studies reporting both the MCID and the PASS. The most widely studied PROMs were the American Shoulder and Elbow Surgeons (ASES) (range 5.65-9.6 for distribution MCID, 8.5 anchor MCID, 86 anchor PASS); Single Assessment Numeric Evaluation (SANE) (range 11.4-12.4 distribution MCID, 82.5-87.5 anchor PASS); visual analog scale (VAS) (range 1.1-1.7 distribution MCID, 1.5-2.5 PASS); Western Ontario Shoulder Instability Index (WOSI) (range 60.7-254.9 distribution MCID, 126.43 anchor MCID, 571-619.5 anchor PASS); and Rowe scores (range 5.6-8.4 distribution MCID, 9.7 anchor MCID). Notably, no studies reported on substantial clinical benefit (SCB) or maximal outcome improvement (MOI). CONCLUSION: Despite the wide array of available PROMs for assessing shoulder instability surgery outcomes, the availability of clinically significant outcome thresholds such as MCID and PASS remains relatively limited. While MCID has been the most frequently reported metric, there is considerable inter-study variability observed in their values. CLINICAL RELEVANCE: Knowing the outcome thresholds such as MCID and PASS of the PROMs frequently used to evaluate the results of glenohumeral stabilization surgery is fundamental, since they allow us to know what is a clinically significant improvement for the patient.

Posttraumatic Stress Disorder and Type 2 Diabetes Outcomes in Veterans.

Importance: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown. Objective: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD. Design, Setting, and Participants: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to September 30, 2022) to create a cohort of patients aged 18 to 80 years with comorbid PTSD and T2D. Data analysis was performed from March 1 to June 1, 2024. Exposures: Diagnoses of PTSD and T2D. Main Outcomes and Measures: The main outcomes were insulin initiation, poor glycemic control, any microvascular complication, and all-cause mortality. Improvement of PTSD was defined as no longer meeting PTSD diagnostic criteria, per a PTSD Checklist score of less than 33. Entropy balancing controlled for confounding. Survival and competing risk models estimated the association between meeting PTSD criteria and T2D outcomes. Subgroup analyses examined variation by age, sex, race, PTSD severity, and comorbid depression status. Results: The study cohort included 10 002 veterans. More than half of patients (65.3%) were aged older than 50 years and most (87.2%) were men. Patients identified as Black (31.6%), White (62.7%), or other race (5.7%). Before controlling for confounding with entropy balancing, patients who no longer met PTSD diagnostic criteria had similar incidence rates for starting insulin (22.4 vs 24.4 per 1000 person-years), poor glycemic control (137.1 vs 133.7 per 1000 person-years), any microvascular complication (108.4 vs 104.8 per 1000 person-years), and all-cause mortality (11.2 vs 11.0 per 1000 person-years) compared with patients with persistent PTSD. After controlling for confounding, no longer meeting PTSD criteria was associated with a lower risk of microvascular complications (hazard ratio [HR], 0.92 [95% CI, 0.85-0.99]). Among veterans aged 18 to 49 years, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.69 [95% CI, 0.53-0.88]) and all-cause mortality (HR, 0.39 [95% CI, 0.19-0.83]). Among patients without depression, no longer meeting PTSD criteria was associated with a lower risk of insulin initiation (HR, 0.73 [95% CI, 0.55-0.97]). Conclusions and Relevance: The findings of this cohort study of patients with comorbid PTSD and T2D suggest that PTSD is a modifiable risk factor associated with a modest reduction in microvascular complications. Further research is needed to determine whether findings are similar in non-VHA health care settings.

Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in lethal prostate cancer.

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSIs) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood. EXPERIMENTAL DESIGN: We applied targeted cell-free DNA sequencing to 126 mCRPC patients from three academic cancer centers, and separately performed genome-wide cell-free DNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome-positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 mCRPC patients, respectively, to develop and validate a stem-like signature, which we inferred from cell-free DNA. RESULTS: Targeted cell-free DNA sequencing detected AR/enhancer alterations prior to first-line ARSIs which correlated with significantly worse PFS (p = 0.01; HR = 2.12) and OS (p = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (p < 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cell-free DNA revealed enrichment for stemness-associated transcription factors in lethal mCRPC patients. The resulting stemness signature was then validated in a completely held-out cohort of 80 mCRPC patients profiled by tumor RNA sequencing. CONCLUSIONS: We analyzed a total of 220 mCRPC patients, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness.

Development of Preliminary Integrated Health Care Clinical Competencies for United States Doctor of Chiropractic Programs: A Modified Delphi Consensus Process.

Background: There has been rapid growth of chiropractors pursuing career opportunities in both public and private hospitals and other integrated care settings. Chiropractors that prosper in integrated care settings deliver patient-centered care, focus on the institutional mission, understand and adhere to organizational rules, and are proficient in navigating complex systems. The Council on Chiropractic Education Accreditation Standards do not outline specific meta-competencies for integrated care clinical training. Objective: The purpose of this study was to develop preliminary integrated health care competencies for DC programs to guide the advancement of clinical chiropractic education. Methods: A systematic literature search was performed. Articles were screened for eligibility and extracted in duplicate. Domains and seed statements were generated from this literature, piloted at a conference workshop, and evaluated via a modified Delphi consensus process. Of 42 invited, 36 chiropractors participated as panelists. Public comment period yielded 20 comments, none resulting in substantive changes to the competencies. Results: Of 1718 citations, 23 articles met eligibility criteria. After 2 modified Delphi rounds, consensus was reached on all competency statements. A total of 78 competency statements were agreed upon, which encompassed 4 domains and 11 subdomains. The 4 domains were: 1) Collaboration, (2) Clinical Excellence, (3) Communication, and (4) Systems Administration. Conclusion: We identified 78 preliminary competencies appropriate for preparing DC students and early career chiropractors for clinical practice in integrated healthcare settings. Educational programs may consider these competencies for curricular design and reform to strengthen DC program graduates for integrated practice, advanced training, and employment.

The role of emerging elites in the formation and development of communities after the fall of the Roman Empire.

Elites played a pivotal role in the formation of post-Roman Europe on both macro- and microlevels during the Early Medieval period. History and archaeology have long focused on their description and identification based on written sources or through their archaeological record. We provide a different perspective on this topic by integrating paleogenomic, archaeological, and isotopic data to gain insights into the role of one such elite group in a Langobard period community near Collegno, Italy dated to the 6-8th centuries CE. Our analysis of 28 newly sequenced genomes together with 24 previously published ones combined with isotope (Sr, C, N) measurements revealed that this community was established by and organized around a network of biologically and socially related individuals likely composed of multiple elite families that over time developed into a single extended pedigree. The community also included individuals with diverse genetic ancestries, maintaining its diversity by integrating newcomers and groups in later stages of its existence. This study highlights how shifts in political power and migration impacted the formation and development of a small rural community within a key region of the former Western Roman Empire after its dissolution and the emergence of a new kingdom. Furthermore, it suggests that Early Medieval elites had the capacity to incorporate individuals from varied backgrounds and that these elites were the result of (political) agency rather than belonging to biologically homogeneous groups.

Dorsal arachnoid web of the thoracic spine associated with an arachnoid cyst and a presyrinx state as an unexplained cause of thoracic myelopathy: illustrative case.

BACKGROUND: Dorsal thoracic arachnoid web is a rare diagnosis and is not commonly seen in neurosurgical practice. Patients can present with symptoms and signs of thoracic myelopathy in the setting of an arachnoid cyst and a presyrinx state. OBSERVATIONS: A 57-year-old male with a 10-year history of worsening bilateral leg weakness and chronic back pain re-presented to the neurosurgery clinic after being seen by neurology and orthopedic spine surgery. Initial imaging was concerning for myelomalacia and syringomyelia, and repeat delayed computed tomography myelography findings were consistent with an evolving thoracic arachnoid web, now demonstrating spinal cord compression secondary to arachnoid cyst formation and consistent with the signs of thoracic myelopathy. Intraoperative ultrasound displayed the arachnoid web as the cause of the evolving arachnoid cyst, edematous spinal cord, and a presyrinx-like state. The patient underwent surgical decompression, which restored cerebrospinal fluid (CSF) dynamics, resulting in clinical improvement. LESSONS: Dorsal thoracic arachnoid web is a dynamic condition that can occur in the setting of an arachnoid cyst. There appears to be a relationship between dorsal thoracic arachnoid web formation and the presence of an arachnoid cyst resulting from a ball-valve mechanism leading to the creation of a pressure gradient effect that alters CSF fluid dynamics. https://thejns.org/doi/10.3171/CASE24313.

Polarization-sensitive optical coherence tomography and scleral collagen fiber orientation in osteogenesis imperfecta.

Osteogenesis imperfecta (OI), a rare genetic connective tissue disorder, primarily arises from pathogenic variants affecting the production or structure of collagen type I. In addition to skeletal fragility, individuals with OI may face an increased risk of developing ophthalmic diseases. This association is believed to stem from the widespread presence of collagen type I throughout various parts of the eye. However, the precise consequences of abnormal collagen type I on different ocular tissues remain unknown. Of particular significance is the sclera, where collagen type I is abundant and crucial for maintaining the structural integrity of the eye. Recent research on healthy individuals has uncovered a unique organizational pattern of collagen fibers within the sclera, characterized by fiber arrangement in both circular and radial layers around the optic nerve head. While the precise function of this organizational pattern remains unclear, it is hypothesized to play a role in providing mechanical support to the optic nerve. The objective of this study is to investigate the impact of abnormal collagen type I on the sclera by assessing the fiber organization near the optic nerve head in individuals with OI and comparing them to healthy individuals. Collagen fiber orientation of the sclera was measured using polarization-sensitive optical coherence tomography (PS-OCT), an extension of the conventional OCT that is sensitive to materials that exhibit birefringence (axial changes in light refraction). Birefringence was quantified and used as imaging contrast to extract collagen fiber orientation as well as the thickness of the radially oriented scleral layer. Three individuals with OI, exhibiting different degrees of disease severity, were assessed and analyzed, along with seventeen healthy individuals. Mean values obtained from individuals with OI were descriptively compared to those of the healthy participant group. PS-OCT revealed a similar orientation pattern of scleral collagen fibers around the optic nerve head between OI individuals and healthy individuals. However, two OI participants exhibited reduced mean birefringence of the radially oriented scleral layer compared to the healthy participant group (OI participant 1 oculus dexter et sinister (ODS): 0.34°/µm, OI participant 2: ODS 0.26°/µm, OI participant 3: OD: 0.29°/µm, OS: 0.28°/µm, healthy participants: ODS 0.38 ± 0.05°/µm). The radially oriented scleral layer was thinner in all OI participants although within ±2 standard deviations of the mean observed in healthy individuals (OI participant 1 OD: 101 µm, OS 104 µm, OI participant 2: OD 97 µm, OS 98 µm, OI participant 3: OD: 94 µm, OS 120 µm, healthy participants: OD 122.8 ± 13.6 µm, OS 120.8 ± 15.1 µm). These findings imply abnormalities in collagen organization or composition, underscoring the necessity for additional research to comprehend the ocular phenotype in OI.

DOSage of Exercise for chronic low back pain disorders (DOSE): protocol for a systematic review with dose-response network meta-analysis.

Chronic low back disorders are the leading cause of direct and indirect healthcare burden globally. Exercise training improves pain intensity, mental health and physical function. However, the optimal prescription variables are unknown. We aim to compare the efficacy of various exercise dosages for chronic low back disorders to identify the optimal prescription variables. Six databases (Medline, SPORTDiscus, CINAHL, PsycINFO, EMBASE and CENTRAL), trial registries (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) and reference lists of prior systematic reviews will be searched, and we will conduct forward and backward citation tracking. We will include peer-reviewed randomised controlled trials (individual, cluster or cross-over trials) published in English or German language comparing exercise training to other exercise training or non-exercise training interventions (conservative, non-surgical, non-pharmacological, non-invasive treatments, placebo, sham, usual/standard care, no-treatment control, waitlist control) in adults with chronic low back disorders. Outcomes will include pain intensity, disability, mental health, adverse events, adherence rate, dropout rate and work capacity. Version 2 of the Cochrane risk-of-bias tool will be employed. The dose will be categorised as cumulative dose (total and weekly minutes of exercise training) and individual dose prescription variables (intervention duration, session duration, frequency and intensity). Dose-response model-based network meta-analysis will be used to assess the comparative efficacy of different exercise doses to determine a dose-response relationship. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation. Information about optimal exercise training dosage will help in enhancing treatment outcomes.

Decoding RNA Metabolism by RNA-linked CRISPR Screening in Human Cells.

RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC screens highlight modular interactions between gene networks regulating splicing, translation, and decay of mRNAs. When combined with biochemical fractionation of polysomes, ReLiC reveals striking pathway-specific coupling between growth fitness and mRNA translation. Perturbing different components of the translation and proteostasis machineries have distinct effects on ribosome occupancy, while perturbing mRNA transcription leaves ribosome occupancy largely intact. Isoform-selective ReLiC screens capture differential regulation of intron retention and exon skipping by SF3b complex subunits. Chemogenomic screens using ReLiC decipher translational regulators upstream of mRNA decay and uncover a role for the ribosome collision sensor GCN1 during treatment with the anti-leukemic drug homoharringtonine. Our work demonstrates ReLiC as a versatile platform for discovering and dissecting regulatory principles of human RNA metabolism.

Analytical Procedure Development and Proposed Established Conditions: A Case Study of a Mass Spectrometry Based NDSRI Analytical Procedure.

With the finalization of the ICH Q14 Analytical Procedure Development guideline, how to apply enhanced approaches (such as analytical quality by design (AQbD)) to develop an analytical procedure, and to propose Established Conditions (ECs) and corresponding reporting categories, is increasingly being discussed. To gain practical experience in applying an enhanced approach for method development and identifying ECs, we developed, validated, and implemented an analytical procedure for a nitrosamine drug substance-related impurity (NDSRI). Here, as an example of the application of Q12 Lifecycle Management guideline principles in regards to analytical procedures, we briefly elaborate how: 1) the principles documented in the ICH Q14 guideline for analytical procedure development were applied, with the focus on identifying an Analytical Target Profile (ATP), knowledge management and risk assessment; 2) analytical procedure robustness according to the recommendations in ICH Q2(R2) Validation of Analytical Procedure guideline and Q14, were evaluated; and 3) mass spectrometry ECs and associated proposed reporting categories were proposed.

Prediction of plant complex traits via integration of multi-omics data.

The formation of complex traits is the consequence of genotype and activities at multiple molecular levels. However, connecting genotypes and these activities to complex traits remains challenging. Here, we investigate whether integrating genomic, transcriptomic, and methylomic data can improve prediction for six Arabidopsis traits. We find that transcriptome- and methylome-based models have performances comparable to those of genome-based models. However, models built for flowering time using different omics data identify different benchmark genes. Nine additional genes identified as important for flowering time from our models are experimentally validated as regulating flowering. Gene contributions to flowering time prediction are accession-dependent and distinct genes contribute to trait prediction in different genotypes. Models integrating multi-omics data perform best and reveal known and additional gene interactions, extending knowledge about existing regulatory networks underlying flowering time determination. These results demonstrate the feasibility of revealing molecular mechanisms underlying complex traits through multi-omics data integration.

One-step genome engineering in bee gut bacterial symbionts.

Mechanistic understanding of interactions in many host-microbe systems, including the honey bee microbiome, is limited by a lack of easy-to-use genome engineering approaches. To this end, we demonstrate a one-step genome engineering approach for making gene deletions and insertions in the chromosomes of honey bee gut bacterial symbionts. Electroporation of linear or non-replicating plasmid DNA containing an antibiotic resistance cassette flanked by regions with homology to a symbiont genome reliably results in chromosomal integration. This lightweight approach does not require expressing any exogenous recombination machinery. The high concentrations of large DNAs with long homology regions needed to make the process efficient can be readily produced using modern DNA synthesis and assembly methods. We use this approach to knock out genes, including genes involved in biofilm formation, and insert fluorescent protein genes into the chromosome of the betaproteobacterial bee gut symbiont Snodgrassella alvi. We are also able to engineer the genomes of multiple strains of S. alvi and another species, Snodgrassella communis, which is found in the bumble bee gut microbiome. Finally, we use the same method to engineer the chromosome of another bee symbiont, Bartonella apis, which is an alphaproteobacterium. As expected, gene knockout in S. alvi using this approach is recA-dependent, suggesting that this straightforward procedure can be applied to other microbes that lack convenient genome engineering methods. IMPORTANCE: Honey bees are ecologically and economically important crop pollinators with bacterial gut symbionts that influence their health. Microbiome-based strategies for studying or improving bee health have utilized wild-type or plasmid-engineered bacteria. We demonstrate that a straightforward, single-step method can be used to insert cassettes and replace genes in the chromosomes of multiple bee gut bacteria. This method can be used for investigating the mechanisms of host-microbe interactions in the bee gut community and stably engineering symbionts that benefit pollinator health.

Source and variation of the amazing live Sea-Monkey microbiome.

An embryonic diapause in unfavourable conditions has allowed brine shrimp to thrive in hypersaline environments and, unexpectedly, mail-order sachets and small, novelty tanks. Marketed as Sea-Monkeys®, each kit involves a 3-step process to generate adult Artemia within a matter of weeks. Whether these kits also allow for the maintenance of a host-associated microbiome is unclear. Therefore, comparing five replicate tanks under the same culture conditions, we sequenced the 16S ribosomal small subunit (SSU) gene to analyse bacterial community compositions in adults, their surrounding tank water, and their feed. Adult Sea-Monkeys® harboured a bacterial microbiome that was clearly distinguishable from the tank water and food. Furthermore, individual tanks had a notable effect on fine-scale microbiome variation. Several Sea-Monkey bacterial variants appeared absent in environmental samples and included genera (Leucobacter and Microbacterium) known to confer desiccation resistance in other hosts. Although Sea-Monkeys® taxonomy is unclear, phylogenetic inference of the cytochrome c oxidase I (COXI) gene from the host animal suggests Sea-Monkeys® belong to the Artemia franciscana 'superspecies'. Overall, Sea-Monkeys® kits appear to be a convenient and scalable mesocosm for the study of host-microbiome interactions and could serve as a useful tool for future invertebrate microbiome research, outreach, and education.

Metabolomic analysis combined with machine learning algorithms enables the evaluation of postharvest pecan color stability.

Nut kernel color is a crucial quality indicator affecting the consumers first impression of the product. While growing evidence suggests that plant phenolics and their derivatives are linked to nut kernel color, the compounds (biomarkers) responsible for kernel color stability during storage remain elusive. Here, pathway-based metabolomics with machine learning algorithms were employed to identify key metabolites of postharvest pecan color stability. Metabolites in phenylpropanoid, flavonoid, and anthocyanin biosynthetic pathways were analyzed in the testa of nine pecan cultivars using liquid chromatography-mass spectrometry. With color measurements, different machine learning models were compared to find relevant biomarkers of pecan color phenotypes. Results revealed potential marker compounds that included flavonoid precursors and anthocyanidins as well as anthocyanins (e.g., peonidin, delphinidin-3-O-glucoside). Our findings provide a foundation for future research in the area, and will help select genes/proteins for the breeding of pecans with stable and desirable kernel color.

T32 programs in emergency medicine: A report from the ACEP-SAEM Federal Research Funding Workgroup.

Advancing care in Emergency Medicine (EM) requires the development of well-trained researchers, but our specialty has lower amounts of research funding compared to similar medical fields. Increasing the number of pathways available for research training supports the growth of new investigators. To address the need for more EM researchers, the Society of Academic Emergency Medicine and the American College of Emergency Physicians convened a Federal Research Funding Workgroup. Here, we report the workgroup recommendations regarding the creation of Research Training Fellowships using the T32 grant structure sponsored by the National Institutes of Health. After reviewing the history of NIH-grant supported research fellowships in EM, we outline the rationale and describe the core components of T32-supported research fellowships, including program design, fellow evaluation, and recruitment considerations.

Hepatic Sinusoidal Disorders.

Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.

Machine Learning Models Can Define Clinically Relevant Bone Density Subgroups based on Patient Specific Calibrated CT Scans in Patients Undergoing Reverse Shoulder Arthroplasty.

BACKGROUND: Reduced bone density is recognized as a predictor for potential complications in reverse shoulder arthroplasty (RSA). While humeral and glenoid planning based on preoperative computed tomography (CT) scans assist in implant selection and position, reproducible methods for quantifying the patients' bone density are currently not available. The purpose of this study was to perform bone density analyses including patient specific calibration in an RSA cohort based on preoperative CT imaging. It was hypothesized that preoperative CT bone density measures would provide objective quantification of the patients' humeral bone quality. METHODS: This study consisted of three parts, (1) analysis of a patient-specific calibration method in cadaveric CT scans, (2) retrospective application in a clinical RSA cohort, and (3) clustering and classification with machine learning models. Forty cadaveric shoulders were scanned in a clinical CT and compared regarding calibration with density phantoms, air muscle, and fat (patient-specific) or standard Hounsfield unit. Post-scan patient-specific calibration was used to improve the extraction of three-dimensional regions of interest for retrospective bone density analysis in a clinical RSA cohort (n=345). Machine learning models were used to improve the clustering (Hierarchical Ward) and classification (Support Vector Machine (SVM)) of low bone densities in the respective patients. RESULTS: The patient-specific calibration method demonstrated improved accuracy with excellent intraclass correlation coefficients (ICC) for cylindrical cancellous bone densities (ICC>0.75). Clustering partitioned the training data set into a high-density subgroup consisting of 96 patients and a low-density subgroup consisting of 146 patients, showing significant differences between these groups. The SVM showed optimized prediction accuracy of low and high bone densities compared to conventional statistics in the training (accuracy=91.2%; AUC=0.967) and testing (accuracy=90.5 %; AUC=0.958) data set. CONCLUSION: Preoperative CT scans can be used to quantify the proximal humeral bone quality in patients undergoing RSA. The use of machine learning models and patient-specific calibration on bone mineral density demonstrated that multiple 3D bone density scores improved the accuracy of objective preoperative bone quality assessment. The trained model could provide preoperative information to surgeons treating patients with potentially poor bone quality.

Long-term disease-specific quality of life after laparoscopic Nissen fundoplication in patients with borderline GERD.

BACKGROUND: Historically, DeMeester score over 14.7 has been used to diagnose GERD. The 2022 American Gastroenterological Association clinical guidelines define GERD based on acid exposure time (AET) instead of DeMeester score. We aim to compare outcomes after laparoscopic Nissen fundoplication (LNF) in patients based on differing GERD diagnostic criteria. METHODS: Patients who underwent first-time LNF between 2009 and 2017 were identified. Demographics, objective GERD evaluation, and outcomes were maintained in an IRB-approved database. Disease-specific quality of life was assessed with a survey (GERD-HRQL) with higher values representing more symptomatic disease. Descriptive statistics, Fischer's exact test and logistic regression were used to analyze the data, p-value < 0.05. RESULTS: 225 patients were stratified into two groups: borderline GERD (AET 4-6%, n = 25.11%) and GERD (AET ≥ 6%, n = 200.89%). The mean age was 50.1 ± 13.4 years and 169 (75%) were female. Baseline GERD-HRQL was lower in the borderline group (24.3 vs 30.0, p = 0.031). Short-term (5 weeks [IQR 4, 8]), medium-term (14 months [IQR 7.25, 31]) and long-term (6.75 years [IQR 5.5, 8]) follow-up was performed. GERD-HRQL scores did not differ between borderline and GERD patients at short-(6.0 vs 7.1, p = 0.630), medium-(12.0 vs 12.1, p = 0.818), or long-term follow-up (10.0 vs 9.0, p = 0.757). The absolute long-term improvement in GERD-HRQL was -12.3 (p = 0.022) vs. -21.3 (p < 0.001). At long-term follow-up there was no difference in PPI use (50% vs 47%, p = 0.852), satisfaction (58% vs 76%, p = 0.187), willingness to repeat the procedure given the benefit of hindsight (75% vs 85%, p = 0.386), or need for reoperation (14% vs 13%, p = 0.910). CONCLUSION: Both patients with borderline GERD and GERD achieve GERD-HRQL improvements at 7 years following laparoscopic Nissen fundoplication and demonstrate similar long-term PPI usage and satisfaction with surgical results. Borderline GERD patients have lower GERD-HRQL at baseline, and thus have smaller improvements in their QOL scores. Anti-reflux surgery should be considered for patients with a diagnosis of borderline GERD refractory to medical therapy.

PET/CT targeted tissue sampling reveals intravenously administered HGN194 IgG1 affects HIV distribution after rectal exposure.

Neutralizing monoclonal antibodies hold great potential for prevention of human immunodeficiency virus (HIV) acquisition. IgG is the most abundant antibody in human serum, has a long half-life, and potent effector functions, making it a prime candidate for an HIV prevention therapeutic. We combined Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interaction with mucosal barriers and viral penetration in colorectal tissue two hours after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found in mesenteric lymph nodes. Taken together, our results show that HGN194 IgG1 does not prevent virions from penetrating into the colorectal mucosa but may perturb HIV virion access to the lymphatic system.