The impact of hepatic and splenic volumetric assessment in imaging for chronic liver disease: a narrative review.

Chronic liver disease is responsible for significant morbidity and mortality worldwide. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) can fully visualise the liver and adjacent structures in the upper abdomen providing a reproducible assessment of the liver and biliary system and can detect features of portal hypertension. Subjective interpretation of CT and MRI in the assessment of liver parenchyma for early and advanced stages of fibrosis (pre-cirrhosis), as well as severity of portal hypertension, is limited. Quantitative and reproducible measurements of hepatic and splenic volumes have been shown to correlate with fibrosis staging, clinical outcomes, and mortality. In this review, we will explore the role of volumetric measurements in relation to diagnosis, assessment of severity and prediction of outcomes in chronic liver disease patients. We conclude that volumetric analysis of the liver and spleen can provide important information in such patients, has the potential to stratify patients' stage of hepatic fibrosis and disease severity, and can provide critical prognostic information. CRITICAL RELEVANCE STATEMENT: This review highlights the role of volumetric measurements of the liver and spleen using CT and MRI in relation to diagnosis, assessment of severity, and prediction of outcomes in chronic liver disease patients. KEY POINTS: Volumetry of the liver and spleen using CT and MRI correlates with hepatic fibrosis stages and cirrhosis. Volumetric measurements correlate with chronic liver disease outcomes. Fully automated methods for volumetry are required for implementation into routine clinical practice.

Elevated nuclear TDP-43 induces constitutive exon skipping.

BACKGROUND: Cytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generate in vitro and in vivo model systems. METHODS: We analyzed RNA-seq datasets from mouse and human neurons overexpressing TDP-43 to explore species specific splicing patterns. We explored the dynamics between TDP-43 levels and exon repression in vitro. Furthermore we analyzed human brain samples and publicly available RNA datasets to explore the relationship between exon repression and disease. RESULTS: Our study shows that excessive levels of nuclear TDP-43 protein lead to constitutive exon skipping that is largely species-specific. Furthermore, while aberrant exon skipping is detected in some human brains, it is not correlated with disease, unlike the incorporation of cryptic exons that occurs after loss of TDP-43. CONCLUSIONS: Our findings emphasize the need for caution in interpreting TDP-43 overexpression data and stress the importance of controlling for exon skipping when generating models of TDP-43 proteinopathy.

Comparison of Long-Term Healthcare Cost and Utilisation of Nonoperative and Surgical Management of Thumb CMC Arthritis.

Background: Thumb carpometacarpal joint (CMC) osteoarthritis is the most symptomatic hand arthritis but the long-term healthcare burden for managing this condition is unknown. We sought to compare total healthcare cost and utilisation for operative and nonoperative treatments of thumb CMC arthritis. Methods: We conducted a retrospective longitudinal analysis using a large nationwide insurance claims database. A total of 18,705 patients underwent CMC arthroplasty (trapeziectomy with or without ligament reconstruction tendon interposition) or steroid injections between 1 October 2015 and 31 December 2018. Primary outcomes, healthcare utilisation and costs were measured from 1 year pre-intervention to 3 years post-intervention. Generalised linear mixed effect models adjusted for potentially confounding factors such as the Elixhauser comorbidity score with propensity score matching were applied to evaluate the association between the primary outcomes and treatment type. Results: A total of 13,646 patients underwent treatment through steroid injections, and 5,059 patients underwent CMC arthroplasty. At 1 year preoperatively, the surgery group required $635 more healthcare costs (95% CI [594.28, 675.27]; p < 0.001) and consumed 42% more healthcare utilisation (95% CI [1.38, 1.46]; p < 0.0001) than the steroid injection group. At 3 years postoperatively, the surgery group required $846 less healthcare costs (95% CI [-883.07, -808.51], p < 0.0001) and had 51% less utilisation (95% CI [0.49, 0.53]; p < 0.0001) annually. Cumulatively over 3 years, the surgical group on average was $4,204 costlier than its counterpart secondary to surgical costs. Conclusions: CMC arthritis treatment incurs high healthcare cost and utilisation independent of other medical comorbidities. At 3 years postoperatively, the annual healthcare cost and utilisation for surgical patients were less than those for patients who underwent conservative management, but this difference was insufficient to offset the initial surgical cost. Level of Evidence: Level III (Therapeutic).

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

REPORTED PRICES FOR HIGH VOLUME HAND SURGERY IN THE ERA OF PRICE TRANSPARENCY: IMPLICATIONS FOR FUTURE POLICY ITERATIONS.

BACKGROUND: In 2021, the United States enacted a law requiring hospitals to report prices for healthcare services. Across several healthcare services, poor compliance and wide variation in pricing was found. This study aims to investigate variation in reporting and listed prices by hospital features for high-volume hand surgeries including Carpal Tunnel release, Trigger Finger Release, De Quervain Tenosynovitis Release, and Carpometacarpal Arthroplasty. METHODS: The Turquoise Health price transparency database was used to obtain listed prices and linked to hospital characteristics from the 2021 Annual American Hospital Association Survey. This study used descriptive statistics and generalized linear regression. RESULTS: The analytic cohort included 2,652 hospitals from across the US. The highest rate of price reporting was in the Midwest (52%, n=836) and lowest in the South (39%, n=925). Compared to commercial insurers, ($3,609, 95% CI: $3,414 to $3,805) public insurance rates were significantly lower (Medicare: $1,588, 95% CI: $1,484 to $1,693, adjusted difference = -$2,021, p<0.001, Medicaid: $1,403, (95% CI: $1,194 to $1,612, adjusted difference = -$2,206, p<0.001). Listed rates for self-pay patients were not statistically different from commercial rates. CONCLUSIONS: Although pricing for high volume elective hand surgeries is frequently reported, a high proportion of hospitals do not report prices. These data highlight the need for future transparency policy to include pricing for high-volume hand surgery to give patients the ability to make financially informed choices. These results are a valuable aid for surgeons and patients to promote financially conscious decisions.

Etiologies and Impact of Exclusion Rates for Transcatheter Mitral and Tricuspid Valve Structural Heart Clinical Trials at a High-Volume Quaternary Care Hospital.

There are various devices under clinical investigation for transcatheter mitral valve intervention and transcatheter tricuspid valve intervention (TTVI); however, the exclusion rates remain high. We aimed to investigate the exclusion rates for transcatheter mitral valve repair (TMVr), transcatheter mitral valve replacement (TMVR), transcatheter tricuspid valve repair (TTVr), and transcatheter tricuspid valve replacement (TTVR). There were 129 patients who were referred to St. Francis Hospital & Heart Center valve clinic and completed screening between January 2021 and July 2022. The causes for exclusion were classified into 4 categories: patient withdrawal, anatomic unsuitability, clinical criteria, and medical futility. In 129 patients, the exclusion rates for TMVr, TMVR, TTVr, and TTVR were 81%, 85%, 91%, and 87%, respectively. Patient withdrawal and medical futility were leading etiologies for exclusion, followed by anatomic unsuitability. TMVr had the highest rate of patient withdrawal (64%) and the lowest anatomic unsuitability (5%) because of short posterior leaflet length. Replacement interventions have a higher anatomic unsuitability (33%) than repair interventions (17%) (p = 0.04). Most exclusions of anatomic unsuitability were because of mitral stenosis or small annulus size for TMVR and large annulus size for TTVR. A total of 50% of exclusions from TTVr were because of the presence of pacemaker/defibrillator leads. In patients excluded from their respective trials, patients being referred for TMVr had the highest recurrent hospitalization and repair group had a higher mortality (p <0.01 and p = 0.01, respectively). In conclusion, the exclusion rates for transcatheter mitral valve intervention and TTVI trials remain high because of various reasons, limiting patient enrollment and treatment. This supports the need for further device improvement or exploring alternative means of therapy.

A Geospatial Analysis of Hand Trauma Care: A Statewide Cross-Sectional Study.

BACKGROUND: Traumatic hand injuries often present with high acuity, but little is known about the influence of geospatial and socioeconomic factors on the timely delivery of care. METHODS: This cross-sectional study used the Michigan Trauma Quality Improvement Program database, a state-wide registry with 35 level I or II trauma centers. Adult patients sustained hand trauma requiring urgent operative treatment between 2016 and 2021. Zip codes of injury location were linked with the corresponding percentile score on the Area Deprivation Index (ADI), a comprehensive measure of neighborhood disadvantage. Multiple regression analyses were used to determine associations of patient, injury and geospatial characteristics with the odds of sustaining acute hand trauma and time to operative treatment. RESULTS: Among 1,826 patients, the odds of sustaining acute hand trauma based on the ADI followed a bimodal distribution. Female sex, smoking, obesity, work-related injury and residence in a minor city were associated with increased odds, while younger age, comorbidities, and rural residence were associated with decreased odds. For 388 patients who underwent surgery within 48 hours, time to treatment was significantly increased in the highest ADI quintile, for patients who underwent fracture fixation, and for those with severe global injury severity. Multi-system injuries, moderate global injury severity and direct admission to an orthopaedic service were associated with shorter times to treatment. CONCLUSIONS: Patients in areas with greater neighborhood disadvantage may experience delayed operative care after acute hand trauma. This study highlights the importance of considering underserved populations and geospatial factors when determining the allocation of hand surgery resources. LEVEL OF EVIDENCE: Prognostic Level III.

Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature.

INTRODUCTION: Viral persistence is one of the main hypotheses explaining the presence of post-COVID symptoms. This systematic review investigated the presence of SARS-CoV-2 RNA in plasma, stool, urine, and nasal/oral swab samples in individuals with post-COVID symptomatology. CONTENT: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to November 25th, 2023. Articles investigating the persistence of SARS-CoV-2 RNA in plasma, stool, urine or nasal/oral swab samples in patients with post-COVID symptoms were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. SUMMARY: From 322 studies identified, six studies met all inclusion criteria. The sample included 678 COVID-19 survivors (52 % female, aged from 29 to 66 years). The methodological quality was moderate in 88 % of the studies (n=5/6). Three papers investigated the presence of SARS-CoV-2 RNA in plasma, three studies in nasal/oral swabs, two studies in stool samples, one in urine and one in saliva. The follow-up was shorter than two months (<60 days after) in 66 % of the studies (n=4/6). The prevalence of SARS-CoV-2 RNA ranged from 5 to 59 % in patients with post-COVID symptoms the first two months after infection, depending on the sample tested, however, SARS-CoV-2 RNA was also identified in COVID-19 survivors without post-COVID symptoms (one study). OUTLOOK: Available evidence can suggest the presence of persistent SARS-CoV-2 RNA in post-COVID patients in the short term, although the biases within the studies do not permit us to make firm assumptions. The association between post-COVID symptoms and SARS-CoV-2 RNA in the samples tested is also conflicting. The lack of comparative group without post-COVID symptoms limits the generalizability of viral persistence in post-COVID-19 condition.

The Contemporary Management of Temporomandibular Joint Intra-Articular Pain and Dysfunction.

The understanding of the causes of temporomandibular joint pain and dysfunction has evolved over 50 years. Historically, the term internal derangement has been used to describe the abnormal relationship between the articular disc, condyle, and glenoid fossa, which was thought to correlate with patient symptoms. It is now known that the pathophysiology of intra-articular pain and dysfunction (IPD) involves synovitis, capsular impingement, symptomatic disc displacement, or a combination of these. Symptomatic disc displacement should only be considered to be a potential source of IPD after synovitis and capsular impingement have been treated. This philosophy provides the opportunity for most patients with IPD to be initially treated nonsurgically or with minimally invasive procedures such as arthrocentesis or arthroscopy.

Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection. METHODS: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom. RESULTS: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I2 ≥ 75%). CONCLUSION: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19.

The use of the E-value for sensitivity analysis.

Observational research designs enable clinicians to investigate topics for which randomized-controlled trials may be difficult to conduct. However, the lack of randomization in observational studies increases the likelihood of confounders introducing bias to study results. Analytical methods such as propensity score matching and regression analysis are employed to reduce the effects of such confounding, mainly by determining characteristics of patient groups and adjusting for measured confounders. Sensitivity analyses are subsequently applied to elucidate the extent to which study results could still be affected by unmeasured confounding. The E-value is one such approach. By presenting a value that quantifies the strength of unmeasured confounding necessary to negate the observed results, the E-value is a useful heuristic concept for assessing the robustness of observational studies. This article provides an introductory overview of how the E-value can be evaluated and presented in clinical research studies.

Evaluating treatment response following locoregional therapy for hepatocellular carcinoma: A review of the available serological and radiological tools for assessment.

Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer-related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non-curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post-treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

Elevated nuclear TDP-43 induces constitutive exon skipping.

Cytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generate in vitro and in vivo model systems. Our study shows that excessive levels of nuclear TDP-43 protein lead to constitutive exon skipping that is largely species-specific. Furthermore, while aberrant exon skipping is detected in some human brains, it is not correlated with disease, unlike the incorporation of cryptic exons that occurs after loss of TDP-43. Our findings emphasize the need for caution in interpreting TDP-43 overexpression data, and stress the importance of controlling for exon skipping when generating models of TDP-43 proteinopathy. Understanding the subtle aspects of TDP-43 toxicity within different subcellular locations is essential for the development of therapies targeting neurodegenerative disease.

Off-Vertical Body Orientation Delays the Perceived Onset of Visual Motion.

The integration of vestibular, visual and body cues is a fundamental process in the perception of self-motion and is commonly experienced in an upright posture. However, when the body is tilted in an off-vertical orientation these signals are no longer aligned relative to the influence of gravity. In this study, the perceived timing of visual motion was examined in the presence of sensory conflict introduced by manipulating the orientation of the body, generating a mismatch between body and vestibular cues due to gravity and creating an ambiguous vestibular signal of either head tilt or translation. In a series of temporal-order judgment tasks, participants reported the perceived onset of a visual scene simulating rotation around the yaw axis presented in virtual reality with a paired auditory tone while in an upright, supine and side-recumbent body position. The results revealed that the perceived onset of visual motion was further delayed from zero (i.e., true simultaneity between visual onset and a reference auditory tone) by approximately an additional 30 ms when viewed in a supine or side-recumbent orientation compared to an upright posture. There were also no significant differences in the timing estimates of the visual motion between all the non-upright orientations. This indicates that the perceived timing of visual motion is negatively impacted by the presence of conflict in the vestibular and body signals due to the direction of gravity and body orientation, even when the mismatch is not in the direct plane of the axis of rotation.

Can a Deep Learning Algorithm Improve Detection of Occult Scaphoid Fractures in Plain Radiographs? A Clinical Validation Study.

BACKGROUND: Occult scaphoid fractures on initial radiographs of an injury are a diagnostic challenge to physicians. Although artificial intelligence models based on the principles of deep convolutional neural networks (CNN) offer a potential method of detection, it is unknown how such models perform in the clinical setting. QUESTIONS/PURPOSES: (1) Does CNN-assisted image interpretation improve interobserver agreement for scaphoid fractures? (2) What is the sensitivity and specificity of image interpretation performed with and without CNN assistance (as stratified by type: normal scaphoid, occult fracture, and apparent fracture)? (3) Does CNN assistance improve time to diagnosis and physician confidence level? METHODS: This survey-based experiment presented 15 scaphoid radiographs (five normal, five apparent fractures, and five occult fractures) with and without CNN assistance to physicians in a variety of practice settings across the United States and Taiwan. Occult fractures were identified by follow-up CT scans or MRI. Participants met the following criteria: Postgraduate Year 3 or above resident physician in plastic surgery, orthopaedic surgery, or emergency medicine; hand fellows; and attending physicians. Among the 176 invited participants, 120 completed the survey and met the inclusion criteria. Of the participants, 31% (37 of 120) were fellowship-trained hand surgeons, 43% (52 of 120) were plastic surgeons, and 69% (83 of 120) were attending physicians. Most participants (73% [88 of 120]) worked in academic centers, whereas the remainder worked in large, urban private practice hospitals. Recruitment occurred between February 2022 and March 2022. Radiographs with CNN assistance were accompanied by predictions of fracture presence and gradient-weighted class activation mapping of the predicted fracture site. Sensitivity and specificity of the CNN-assisted physician diagnoses were calculated to assess diagnostic performance. We calculated interobserver agreement with the Gwet agreement coefficient (AC1). Physician diagnostic confidence was estimated using a self-assessment Likert scale, and the time to arrive at a diagnosis for each case was measured. RESULTS: Interobserver agreement among physicians for occult scaphoid radiographs was higher with CNN assistance than without (AC1 0.42 [95% CI 0.17 to 0.68] versus 0.06 [95% CI 0.00 to 0.17], respectively). No clinically relevant differences were observed in time to arrive at a diagnosis (18 ± 12 seconds versus 30 ± 27 seconds, mean difference 12 seconds [95% CI 6 to 17]; p < 0.001) or diagnostic confidence levels (7.2 ± 1.7 seconds versus 6.2 ± 1.6 seconds; mean difference 1 second [95% CI 0.5 to 1.3]; p < 0.001) for occult fractures. CONCLUSION: CNN assistance improves physician diagnostic sensitivity and specificity as well as interobserver agreement for the diagnosis of occult scaphoid fractures. The differences observed in diagnostic speed and confidence is likely not clinically relevant. Despite these improvements in clinical diagnoses of scaphoid fractures with the CNN, it is unknown whether development and implementation of such models is cost effective. LEVEL OF EVIDENCE: Level II, diagnostic study.