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.

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.

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.

Mechanical comparison of straight and pre-bent interlocking nails used for the stabilization of a tibial gap fracture model.

OBJECTIVE: To compare the mechanical behavior of straight (STRT) and pre-bent (BENT) I-Loc angle-stable interlocking nails (AS-ILN) used for stabilization of canine mid-diaphyseal tibial fractures. STUDY DESIGN: In vitro experimental study. SAMPLE POPULATION: Tibial gap fracture models (n = 5/group). METHODS: Tibial models simulating a comminuted mid-diaphyseal fracture were stabilized with either a STRT or BENT I-Loc AS-ILN. Bent nails were contoured to match the 10° tibial recurvatum of a mid-size dog. Constructs were subjected to cyclic eccentric compressive loads followed by ramp load until failure. Construct compliance, maximum compressive load and resistive torque, yield load and angular deformation at 450 N were statistically compared using t-tests (p < .05). Failure modes were described. RESULTS: Compliance was 45% lower in BENT than STRT groups (p < .0001). Constructs in the BENT group sustained ~20% and 34% greater maximum and yield loads, respectively, than STRT constructs. Maximum resistive torques were similar between groups (p = .16). At 450 N, sagittal plane angular deformation increased from 0° to 4° in procurvatum (STRT group) and decreased from 10° to 8° in recurvatum (BENT group-p < .0001). Construct yield failure occurred at the nail isthmus in both groups. CONCLUSION: These results demonstrated that, in a tibial gap fracture model, pre-bending I-Loc AS-ILNs provided mechanical advantages by increasing their ability to resist bending resulting from eccentric compressive loads. CLINICAL SIGNIFICANCE: Pre-bending may reduce the occurrence of tibial nail yield failure. Surgeons should therefore consider pre-bending tibial I-Loc nails to match the bone anatomical recurvatum prior to implantation.

Are Observational Studies on Distal Radius Fracture Treatment Robust? An E-value Approach to Analysis.

BACKGROUND: Reported complication frequencies after distal radius fracture (DRF) treatment vary widely in the literature and are based mostly on observational evidence. Whether that evidence is sufficiently robust to use in practice is controversial. The E-value is an innovative sensitivity analysis that quantitates the robustness of observational evidence against unmeasured confounders, whereby a greater E-value usually implies more robust evidence and vice versa; with DRF complications, this approach can help guide readers to a more confident interpretation of the available evidence. QUESTIONS/PURPOSES: In this study, we sought (1) to compare the complication frequencies among different DRF treatment modalities, and (2) to evaluate the robustness of these observational studies using the E-value as an index for unmeasured confounding. METHODS: We searched PubMed, Embase, and SCOPUS for observational studies on the management of DRFs that were published from January 2001 to July 2021 with the last database search performed on July 31, 2021. All articles that compared different DRF treatment modalities with reported complication frequencies were included to accurately capture the quality of the observational studies in research about DRF. Risk ratios (RRs) of the overall complication and major complication risks were calculated for each subgroup comparison: volar plating versus dorsal plating, casting, external fixation, and percutaneous K-wire fixation. The RRs and their corresponding lower limits of the 95% confidence intervals (CIs) were used to derive the E-values. E-values can have a minimum possible value of 1, which signifies that the treatment-outcome association is not strong and can readily be overturned by unmeasured confounders. By contrast, a large E-value means that the observed treatment-outcome association is robust against unmeasured confounders. We averaged RRs and E-values for the effect estimates and lower limits of CIs across studies in each treatment comparison group. We identified 36 comparative observational studies that met the inclusion criteria. Seven studies compared volar with dorsal plating techniques. Volar plating was also compared with casting (eight studies), external fixation (15 studies), and percutaneous K-wire fixation (six studies). RESULTS: Total and major complication risks did not differ among different DRF treatments. The mean RRs for total and major complications were 1.2 (95% CI 0.4 to 3.9; p = 0.74) and 1.8 (95% CI 0.4 to 11.4; p = 0.52) for the volar versus dorsal plating group; 1.2 (95% CI 0.3 to 11.2; p = 0.87) and 1.5 (95% CI 0.3 to 14.9; p = 0.74) for the volar plating versus casting group; 0.6 (95% CI 0.2 to 2.2; p = 0.33) and 0.8 (95% CI 0.2 to 6.7; p = 0.86) for the volar plating versus external fixation group; and 0.6 (95% CI 0.2 to 2.6; p = 0.47) and 0.7 (95% CI 0.2 to 4.0; p = 0.67) for the volar plating versus K-wire fixation group. The mean E-values for total and major complication frequencies for the between-group comparison ranged from 3.1 to 5.8; these were relatively large in the context of a known complication risk factor, such as high-energy impact (RR 3.2), suggesting a reasonable level of robustness against unmeasured confounding. However, the E-values for lower limits of CIs remained close to 1, which indicates the observed complication frequencies in these studies were likely to have been influenced by unmeasured confounders. CONCLUSION: Complication frequencies did not differ among different DRF treatment modalities, but the observed complication frequencies from most comparative observational studies were less robust against potential unmeasured confounders. The E-value method, or another type of sensitivity analysis, should be implemented in observational hand surgery research at the individual-study level to facilitate assessment of robustness against potential unmeasured confounders. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

Cardiac Risk Stratification in Liver Transplantation: Results of a Tiered Assessment Protocol Based on Traditional Cardiovascular Risk Factors.

Coronary artery disease (CAD) confers increased perioperative risk in patients undergoing liver transplantation (LT). Although routine screening for CAD is recommended, there are limited data on the effectiveness of screening strategies. We evaluated the safety and efficacy of a 3-tiered cardiac risk-assessment protocol that stratifies patients based on age and traditional cardiac risk factors. We peformed a single-center, prospective, observational study of consecutive adult patients undergoing LT assessment (2010-2017). Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) cardiac groups and received standardized investigations with selective use of transthoracic echocardiography (TTE), dobutamine stress echocardiography (DSE), computed tomography coronary angiography (CTCA), and coronary angiography (CA). Primary outcomes were cardiac events (CEs) and cardiovascular death up to 30 days after LT. Overall, 569 patients were included, with 76 patients identified as LR, 256 as IR, and 237 as HR. Cardiac risk factors included diabetes mellitus (26.0%), smoking history (47.3%), hypertension (17.8%), hypercholesterolemia (7.2%), family (17.0%) or prior history of heart disease (6.0%), and obesity (27.6%). Of the patients, 42.0% had ≥2 risk factors. Overall compliance with the protocol was 90.3%. Abnormal findings on TTE, DSE, and CTCA were documented in 3, 23, and 44 patients, respectively, and 12 patients were not listed for transplantation following cardiac assessment (1 LR, 2 IR, and 9 HR). Moderate or severe CAD was identified in 25.4% of HR patients on CTCA following a normal DSE. CEs were recorded in 7 patients (1.2%), with 2 cardiovascular deaths (0.4%). Cardiac risk stratification based on traditional cardiac risk factors with the selective use of DSE, CTCA, and CA is a safe and feasible approach that results in a low perioperative cardiac event rate.

An application of statistical and data mining methods to study the waste charging scheme in Hong Kong.

Waste charging policy is one of the tools used by many countries to solve waste management problems. Before a policy can be fully implemented, it is important to study residents' willingness to pay (WTP) for waste disposal and estimate its effectiveness. This study aims to use data mining models to predict the maximum WTP amount and ratio estimation method to estimate the effectiveness of the proposed waste charging policy in Hong Kong. The results show that the average value of the predicted maximum willingness to pay (WTP) amount varies between HK$36.75 and HK$39.99 based on the data mining models. According to the decision tree models, the predicted maximum WTP amount of the respondents in the training dataset varies between HK$11.3 and HK$94.6. At least 8% of the residents may not afford to pay for waste disposal and need help. At least 5% of the respondents may well afford to pay and may not be motivated by the waste charging policy to reduce waste. It is plausible that over 53% of the respondents may accept the waste charging policy. Assuming the residents will reduce waste to keep the waste disposal expenditure within their maximum WTP amount, the percentage of waste reduction is estimated to be around 12.56-28.12% under the price level of HK$0.11 per liter. The findings may be helpful to the related parties to design and implement the waste charging policy.

Persistent perceptual delay for active head movement onset relative to sound onset with and without vision.

Knowing when the head moves is crucial information for the central nervous system to maintain a veridical representation of the self in the world for perception and action. Previous studies have shown that active head movement onset has to precede a sound by approximately 80 ms to be perceived as simultaneous, suggesting that the perceived timing of head movement is slow. However, this research was conducted with closed eyes. Given that visual information is available for most natural head movements, could perceptual delays in head movement onset be related to removing vision? Here, we examined whether visual information affects the perceived timing of active head movement onset. Participants performed a series of temporal order judgment tasks between their active head movement and an auditory tone presented at various stimulus onset asynchronies. Visual information was either absent (eyes closed) or present while either maintaining fixation on an earth or head-fixed target in the dark or in the light. Results show that head movement onset has to precede a sound by ~76 ms with eyes closed confirming previous work. The results also suggest that head movement onset must still precede a sound when fixating targets in the dark with a trend for the head having to move with less lead time with visual information and with the vestibulo-ocular reflex active or suppressed (~70 to 48 ms). Together, these results suggest that the perception of head movement onset is persistently delayed and is not fully resolved even with full field visual input.

Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems.

BACKGROUND AND AIMS: The American College of Gastroenterology recommends early risk stratification in patients presenting with upper GI bleeding (UGIB). The AIMS65 score is a risk stratification score previously validated to predict inpatient mortality. The aim of this study was to validate the AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB and to compare it with established pre- and postendoscopy risk scores. METHODS: ICD-10 (International Classification of Diseases, Tenth Revision) codes identified patients presenting with UGIB requiring endoscopy. All patients were risk stratified by using the AIMS65, Glasgow-Blatchford score (GBS), pre-endoscopy Rockall, and full Rockall scores. The primary outcome was inpatient mortality. Secondary outcomes were a composite endpoint of inpatient mortality, rebleeding, and endoscopic, radiologic, or surgical intervention; blood transfusion requirement; intensive care unit (ICU) admission; rebleeding; and hospital length of stay. The area under the receiver-operating characteristic curve (AUROC) was calculated for each score. RESULTS: Of the 424 study patients, 18 (4.2%) died and 69 (16%) achieved the composite endpoint. The AIMS65 score was superior to both the GBS (AUROC, 0.80 vs 0.76, P < .027) and the pre-endoscopy Rockall score (0.74, P = .001) and equivalent to the full Rockall score (0.78, P = .18) in predicting inpatient mortality. The AIMS65 score was superior to all other scores in predicting the need for ICU admission and length of hospital stay. AIMS65, GBS, and full Rockall scores were equivalent (AUROCs, 0.63 vs 0.62 vs 0.63, respectively) and superior to pre-endoscopy Rockall (AUROC, 0.55) in predicting the composite endpoint. GBS was superior to all other scores for predicting blood transfusion. CONCLUSION: The AIMS65 score is a simple risk stratification score for UGIB with accuracy superior to that of GBS and pre-endoscopy Rockall scores in predicting in-hospital mortality and the need for ICU admission.

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.

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.

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).

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.

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.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study.

BACKGROUND: Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT. AIM: To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT. METHODS: This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing. RESULTS: Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes. CONCLUSION: Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

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.

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.

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.