bluuebunny/crossref_metadata_2025 huggingface dataset:
USP1-dependent nucleolytic expansion of PRIMPOL-generated nascent DNA strand discontinuities during replication stress
Authors: Nusawardhana Alexandra , Pale Lindsey M , Nicolae Claudia M , Moldovan George-Lucian
Published: January 2024

DNA replication stress-induced fork arrest represents a significant threat to genomic integrity. One major mechanism of replication restart involves repriming downstream of the arrested fork by PRIMPOL, leaving behind a single-stranded DNA (ssDNA) gap. Accumulation of nascent strand ssDNA gaps has emerged as a possible determinant of the cellular hypersensitivity to genotoxic agents in certain genetic backgrounds such as BRCA deficiency, but how gaps are converted into cytotoxic structures is still unclear. Here, we investigate the processing of PRIMPOL-dependent ssDNA gaps upon replication stress induced by hydroxyurea and cisplatin. We show that gaps generated in PRIMPOL-overexpressing cells are expanded in the 3′-5′ direction by the MRE11 exonuclease, and in the 5′-3′ direction by the EXO1 exonuclease. This bidirectional exonucleolytic gap expansion ultimately promotes their conversion into DSBs. We moreover identify the de-ubiquitinating enzyme USP1 as a critical regulator of PRIMPOL-generated ssDNA gaps. USP1 promotes gap accumulation during S-phase, and their expansion by the MRE11 and EXO1 nucleases. This activity of USP1 is linked to its role in de-ubiquitinating PCNA, suggesting that PCNA ubiquitination prevents gap accumulation during replication. Finally, we show that USP1 depletion suppresses DSB formation in PRIMPOL-overexpressing cells, highlighting an unexpected role for USP1 in promoting genomic instability under these conditions.
Two-dimensional semiconductor transistors and integrated circuits for advanced technology nodes
Authors: Li Weisheng , Shen Haoliang , Qiu Hao , Shi Yi , Wang Xinran
Published: January 2024

This Perspective aims to provide a concise survey of current progress and outlook future directions in high-performance transistors and integrated circuits (ICs) based on 2D semiconductors.
Racial and Ethnic Disparities in Adolescent Combustible Tobacco Smoking From 2014 to 2020: Declines Are Lagging Among Non-Hispanic Black Youth
Authors: Mantey Dale S , Omega-Njemnobi Onyinye , Montgomery LaTrice , Kelder Steven H
Published: January 2024

Introduction

We quantified the linear trend in combustible tobacco smoking among adolescents in the United States from 2014 to 2020, and then compared these trends across racial and ethnic categories. We also tested the effect of e-cigarette use on these trends for all-youth and across racial and ethnic categories.

Aims and Methods

We pooled and analyzed seven years of National Youth Tobacco Survey data for n = 124 151 middle and high school students from 2014 to 2020. Weighted logistic regression analyses calculated the annual change in combustible tobacco smoking (ie cigarettes, cigars, and hookah) from 2014 to 2020. Stratified analyses examined linear trends for non-Hispanic White (NHW), NH-Black (NHB), Hispanic/Latino, and NH-Other (NHO) youth. All-models controlled for sex, grade level, and past 30-day e-cigarette use.

Results

Combustible tobacco smoking from 2014 to 2020 dropped by more than 50% for NHW youth, more than 40% for Latino and NHO youth, compared to just 16% among NHB youth. From 2014 to 2020, the odds of combustible tobacco smoking declined by 21.5% per year for NHWs, which was significantly greater than Hispanic/Latinos (17% per year; p = .025), NHOs (15.4% per year; p = .01), and NHBs (5.1% per year; p < .001), adjusting for sex, grade, and e-cigarette use. Trends and disparities in trends by race and ethnicity were observed independent of e-cigarette use.

Conclusions

Combustible tobacco smoking declined for all-youth but at significantly different rates across races and ethnicities. Notably, declines in combustible tobacco smoking are lagging among NHB youth. Interventions are critically needed to address this disparity.

Implications

A direct, evidence-based intervention to reduce combustible tobacco smoking among NHB youth is critically needed. Such tobacco control initiatives should follow the Best Practices for Comprehensive Tobacco Control Framework, incorporating sustainable funding for school-based intervention, public health education, and adult cessation.
Model-Informed Precision Dosing Improves Outcomes in Patients Receiving Vancomycin for Gram-Positive Infections
Authors: Hall Nicole M , Brown Matthew L , Edwards W Seth , Oster Robert A , Cordell Will , Stripling Joshua
Published: January 2024

Background

Consensus guidelines for dosing and monitoring of vancomycin recommend collection of 2 serum concentrations to estimate an area under the curve/minimum inhibitory concentration ratio (AUC/MIC). Use of Bayesian software for AUC estimation and model-informed precision dosing (MIPD) enables pre–steady state therapeutic drug monitoring using a single serum concentration; however, data supporting this approach are limited.

Methods

Adult patients with culture-proven gram-positive infections treated with vancomycin ≥72 hours receiving either trough-guided or AUC-guided therapy were included in this retrospective study. AUC-guided therapy was provided using MIPD and single-concentration monitoring. Treatment success, vancomycin-associated acute kidney injury (VA-AKI), and inpatient mortality were compared using a desirability of outcome ranking analysis. The most desirable outcome was survival with treatment success and no VA-AKI, and the least desirable outcome was death.

Results

The study population (N = 300) was comprised of an equal number of patients receiving AUC-guided or trough-guided therapy. More patients experienced the most desirable outcome in the AUC-guided group compared to the trough-guided group (58.7% vs 46.7%, P = .037). Rates of VA-AKI were lower (21.3% vs 32.0%, P = .037) and median hospital length of stay was shorter (10 days [interquartile range {IQR}, 8–20] vs 12 days [IQR, 8–25]; P = .025) among patients receiving AUC-guided therapy.

Conclusions

AUC-guided vancomycin therapy using MIPD and single-concentration monitoring improved outcomes in patients with culture-proven gram-positive infections. Safety was improved with reduced incidence of VA-AKI, and no concerns for reduced efficacy were observed. Moreover, MIPD allowed for earlier assessment of AUC target attainment and greater flexibility in the collection of serum vancomycin concentrations.
Identifying Individuals at High Risk for HIV and Sexually Transmitted Infections With an Artificial Intelligence–Based Risk Assessment Tool
Authors: Latt Phyu M , Soe Nyi N , Xu Xianglong , Ong Jason J , Chow Eric P F , Fairley Christopher K , Zhang Lei
Published: January 2024

Background

We have previously developed an artificial intelligence–based risk assessment tool to identify the individual risk of HIV and sexually transmitted infections (STIs) in a sexual health clinical setting. Based on this tool, this study aims to determine the optimal risk score thresholds to identify individuals at high risk for HIV/STIs.

Methods

Using 2008–2022 data from 216 252 HIV, 227 995 syphilis, 262 599 gonorrhea, and 320 355 chlamydia consultations at a sexual health center, we applied MySTIRisk machine learning models to estimate infection risk scores. Optimal cutoffs for determining high-risk individuals were determined using Youden's index.

Results

The HIV risk score cutoff for high risk was 0.56, with 86.0% sensitivity (95% CI, 82.9%–88.7%) and 65.6% specificity (95% CI, 65.4%–65.8%). Thirty-five percent of participants were classified as high risk, which accounted for 86% of HIV cases. The corresponding cutoffs were 0.49 for syphilis (sensitivity, 77.6%; 95% CI, 76.2%–78.9%; specificity, 78.1%; 95% CI, 77.9%–78.3%), 0.52 for gonorrhea (sensitivity, 78.3%; 95% CI, 77.6%–78.9%; specificity, 71.9%; 95% CI, 71.7%–72.0%), and 0.47 for chlamydia (sensitivity, 68.8%; 95% CI, 68.3%–69.4%; specificity, 63.7%; 95% CI, 63.5%–63.8%). High-risk groups identified using these thresholds accounted for 78% of syphilis, 78% of gonorrhea, and 69% of chlamydia cases. The odds of positivity were significantly higher in the high-risk group than otherwise across all infections: 11.4 (95% CI, 9.3–14.8) times for HIV, 12.3 (95% CI, 11.4–13.3) for syphilis, 9.2 (95% CI, 8.8–9.6) for gonorrhea, and 3.9 (95% CI, 3.8–4.0) for chlamydia.

Conclusions

Risk scores generated by the AI-based risk assessment tool MySTIRisk, together with Youden's index, are effective in determining high-risk subgroups for HIV/STIs. The thresholds can aid targeted HIV/STI screening and prevention.
An Alleged Tension Between non-Classical Logics and Applied Classical Mathematics
Authors: Horvat Sebastian , Toader Iulian D
Published: January 2024

Timothy Williamson has recently argued that the applicability of classical mathematics in the natural and social sciences raises a problem for the endorsement, in non-mathematical domains, of a wide range of non-classical logics. We first reconstruct his argument and present its restriction to the case of quantum logic (QL). Then we show that there is no problematic tension between the applicability of classical mathematical models to quantum phenomena and the endorsement of QL in the reasoning about the latter. Once we identify the premise in Williamson’s argument that turns out to be false when restricted to QL, we argue that the same premise fails for a wider variety of non-classical logics. In the end, we use our discussion to draw some general lessons concerning the relationship between applied logic and applied mathematics.
The effect of total sleep deprivation on working memory: evidence from diffusion model
Authors: Li Jiahui , Cao Yixuan , Ou Simei , Jiang Tianxiang , Wang Ling , Ma Ning
Published: January 2024

Study objectives

Working memory is crucial in human daily life and is vulnerable to sleep loss. The current study investigated the impact of sleep deprivation on working memory from the information processing perspective, to explore whether sleep deprivation affects the working memory via impairing information manipulation.

Methods

Thirty-seven healthy adults attended two counterbalanced protocols: a normal sleep night and a total sleep deprivation (TSD). The N-back and the psychomotor vigilance task (PVT) assessed working memory and sustained attention. Response time distribution and drift-diffusion model analyses were applied to explore cognitive process alterations.

Results

TSD increased the loading effect of accuracy, but not the loading effect of response time in the N-back task. TSD reduced the speed of information accumulation, increased the variability of the speed of accumulation, and elevated the decision threshold only in 1-back task. Moreover, the slow responses of PVT and N-back were severely impaired after TSD, mainly due to increased information accumulation variability.

Conclusions

The present study provides a new perspective to investigate behavioral performance by using response time distribution and drift-diffusion models, revealing that sleep deprivation affected multicognitive processes underlying working memory, especially information accumulation processes.
Sinonasal Quality of Life After Endoscopic Endonasal Skull Base Surgery
Authors: Bateman Emily , Tiano Benjamin , Marino Michael
Published: January 2024

This article is written to provide the reader with an overview of the sinonasal quality-of-life considerations for patients undergoing endoscopic endonasal skull base surgery.
Substance Use Overdose Deaths Among Black and Indigenous Women in Wisconsin: A Review of Death Certificate Data From 2018 to 2020
Authors: Lopez Alexa A. , Luebke Jeneile M. , Redner Ryan , Abusbaitan Hanan , Tarima Sergey
Published: January 2024

Objectives

We are in the midst of an overdose epidemic that has grown during the concurrent COVID-19 pandemic. In Wisconsin, overdose deaths increased 11-fold from 2000 to 2020, with over 1200 deaths in 2020. Because of disparities in substance use initiation, relapse, and treatment success among racially minoritized women, this study's purpose was to investigate overdose death rates among Black and Indigenous women in Wisconsin from 2018 to 2020.

Methods

Overdose death rates were examined under the following parameters: sex, race (Black, Indigenous, White), age, year, and manner of death. Logistic regression analysis was also conducted looking at death count data, with race, age, and year as potential predictor variables.

Results

Death rates (per 100,000) in 2018 were 14.1 (12.6–15.5) for White women, 20.8 (14.7–26.9) for Black women, and 26.5 (10.0–42.9) for Indigenous women; these rates increased in 2020 to 16.4 (14.8–17.9), 32.5 (25.0–40.0), and 59.9 (35.8–84.0) for White, Black, and Indigenous women, respectively. Regression findings illustrated that being Black or Indigenous and aged 15 to 44 or 45 to 64 years were significantly more likely to die from most causes of death (any drug, any opioid, prescription opioid, heroin, synthetic opioids, and cocaine; adjusted odds ratios > 1.25, Ps < 0.001).

Conclusions

This study confirms that deaths in Wisconsin are disproportionately higher in female minoritized populations. Understanding the complex intricacies between the impacts of the COVID-19 pandemic coupled with barriers to treatment access or acceptability in these populations is urgently needed. It will take a multipronged approach to address the overdose epidemic and better serve these marginalized, vulnerable populations.
Effect of Stimulus Bandwidth on the Auditory Steady-State Response in Scalp- and Ear-EEG
Authors: Sergeeva Anna , Bech Christensen Christian , Kidmose Preben
Published: January 2024

Objectives:

The auditory steady-state response (ASSR) enables hearing threshold estimation based on electroencephalography (EEG) recordings. The choice of stimulus type has an impact on both the detectability and the frequency specificity of the ASSR. Amplitude modulated pure tones provide the most frequency-specific ASSR, but responses to pure tones are weak. The ASSR can be enhanced by increasing the bandwidth of the stimulus, but this comes at the cost of a decrease in the frequency specificity of the measured response. The objective of the present study is to investigate the relationship between stimulus bandwidth and ASSR amplitude.

Design:

The amplitude of ASSR was measured for five types of stimuli: 1 kHz pure tone and band-pass noise with 1/3, 1/2, 1, and 2 octave bandwidths centered at 1 kHz. All stimuli were amplitude modulated with a 40 Hz sinusoid. Responses to all stimulus types were measured at 30, 40, and 50 dB SL. ASSRs were measured concurrently using both conventional scalp-EEG and ear-EEG.

Results:

Stimulus bandwidth and sound intensity were both found to have a significant effect on the ASSR amplitude for scalp- and ear-EEG recordings. In scalp-EEG ASSRs to all bandwidth stimuli were found to be significantly larger than ASSRs to pure tone at low sound intensity. At higher sound intensities, however, significantly larger responses were only obtained for 1- and 2-octave bandwidth stimuli. In ear-EEG, only the ASSR to 2 octave bandwidth stimulus was significantly larger than the ASSR to amplitude modulated pure tones.

Conclusions:

At low presentation levels, even small increases in stimulus bandwidth (1/3 and 1/2 octave) improve the detectability of ASSR in scalp-EEG with little or no impact on the frequency specificity. In comparison, a larger increase in stimulus bandwidth was needed to improve the ASSR detectability in the ear-EEG recordings.
Global, Regional, and National Burdens of Otitis Media From 1990 to 2019: A Population Based Study
Authors: Jin Yan , Yang Xue , Sun Hao , Zhang Jing , Yang Shize , Jiang Shuyi , Song Qingbin , Zhang Guofeng , Ma Bing , Yang Kaijie , Pan Leilei , Huang Longping , Li Yongze
Published: January 2024

Objectives:

Otitis media is one of the most important causes of hearing loss at an early age. Effective vaccination with the routine 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in 2000. It has been gradually replaced by the pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine or the higher-valent 13-valent PCV (PCV-13) since 2010. Data on the change in otitis media burden in recent years are sparse at the global, regional, and national levels.

Design:

The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates, and the average annual percentage changes (AAPCs) in otitis media in geographic populations worldwide from 1990 to 2019. These global trends were further analyzed by subgroup (age, sex, and sociodemographic index [SDI]).

Results:

Globally, the all-age rate of prevalence (AAPC = −0.7, 95% confidence interval [CI] = −0.7 to −0.8), DALYs (AAPC = −1.0, 95% CI = −1.1 to −1.0), and mortality (AAPC = −6.8, 95% CI = −7.3 to −6.4) from otitis media decreased constantly between 1990 and 2019. The all-age rate of incidence decreased sharply between 2000 and 2009 with an AAPC of −1.2 (95% CI = −1.4 to −0.9) and continued the downward trend between 2010 and 2019 (AAPC = −0.2, 95% CI = −0.3 to −0.1). In 2019, children aged 1 to 4 years old had the highest incidence at 29,127.3 per 100,000 population, while young adults under 30 years old accounted for 91.3% of the incident cases. Individuals living in middle-SDI countries had the largest increase in the incidence of otitis media, with an AAPC of 0.3 (95% CI = 0.3 to 0.3) between 1990 and 2019. The incidence and DALYs from otitis media decreased with increasing SDI. Regionally, the largest increase in incidence was observed in high-income Asia Pacific, Eastern Europe, and Western Sub-Saharan Africa between 1990 and 2019. Nationally, the largest increase in the incidence of otitis media was observed in the Republic of Korea, with an AAPC of 0.8 (95% CI = 0.6 to 1.1) in the same time period.

Conclusions:

There have been successful previous endeavors to reduce DALYs and mortality attributed to otitis media on a global scale. The worldwide incidence of otitis media experienced a sharp decline following the introduction of PCV-7 in 2000, and this downward trend persisted in subsequent years with the adoption of PCV-13/pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Continual epidemiological surveillance of otitis media’s global trends, pathogen distribution, and resistance patterns remains imperative.
Variables associated with loss of fixation of retrograde rami screws in minimally displaced lateral compression type 1 pelvic ring injuries
Authors: Tucker Nicholas J , Stacey Stephen , Kim Ye Joon , DeLeon Jorge , Richard Raveesh , Heare Austin , Mauffrey Cyril , Parry Joshua A
Published: January 2024

OBJECTIVES:

To evaluate variables associated with loss of fixation of retrograde rami screws in the treatment of stress-positive minimally displaced lateral compression type 1 (LC1) injuries.

METHODS:

Design:

Retrospective comparative study

Setting:

Level one trauma center

Patient Selection Criteria:

Stress-positive minimally displaced (<1 cm) LC1 pelvic ring injuries treated with retrograde rami screws

Outcome Measures and Comparisons
: Loss of fixation, defined as >5 mm of pelvic fracture displacement based on the radiographic tear-drop distance, or >5 mm of implant displacement on follow-up radiographs; Revision surgery for loss of fixation

RESULTS:

38 patients with 40 retrograde rami screws were analyzed. Median patient age was 64 years (IQR 42.5 to 73.3 years), 71.1% (n=27/38) were female, 52.6% (n=20/38) of injuries were secondary to low-energy mechanisms. Loss of fixation occurred in 17.5% (n=7/40) of screws with 10% (n=4/40) requiring revision surgery. Unicortical rami screws failed at a significantly higher rate than bicortical screws (62.5% (5/8) vs. 3.1% (1/32); observed difference (OD) 59.4%, 95% confidence interval (CI) 22.7% to 85.5%; p=0.0005). Other variables associated with loss of fixation included dynamic displacement on stress radiographs (22.1 vs. 15.4 mm; OD 6.6 mm, CI 2.0 to 11.3; p=0.02), unicortical screws (83.3% vs. 8.8%; OD -74.5%, CI -95.6% to -32.3%; p=0.0005), short screws ending medial to the acetabular sourcil (50.0% vs. 8.8%; OD 41.1%, CI 2.7% to 75.0%; p=0.03), and partially-threaded screws (66.7% vs. 23.5%; OD 43.1%, CI 1.1% to 73.9%; p=0.04). On univariate analysis, patients who had a loss of fixation were more likely to have greater dynamic displacement on stress radiographs (22.0 vs. 15.2 mm; median difference (MD) 5.6 mm, CI -19.2 to 10.3; p=0.04), unicortical rami screws (71.4% vs. 9.1%; PD 62.3%, CI 8.8% to 22.6%; p=0.001), and partially-threaded rami screws (71.4% vs. 21.2%; PD 50.2%, CI 10.0% to 77.6%; p=0.01). The remaining variables had no observed association (p≥0.05) with loss of fixation, including age, gender, BMI, energy of injury mechanism, tobacco use, ASA score, sacral fracture type, distal rami fractures, rami comminution, number of sacral screws, fully-threaded sacral screws, transsacral screws, or rami screw diameter. On multivariate analysis, only unicortical rami screws (p=0.01) remained associated with loss of fixation.

CONCLUSIONS:

Retrograde rami screws had a high rate of loss of fixation in minimally displaced LC1 pelvic ring injuries and this was associated with unicortical screws. These screws should be avoided when possible.

LEVEL OF EVIDENCE:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Contractile Effects of Amphetamine, Pseudoephedrine, Nor-pseudoephedrine (Cathine), and Cathinone on Atrial Preparations of Mice and Humans
Authors: Neumann Joachim , Hußler Wilhelm , Hofmann Britt , Gergs Ulrich
Published: January 2024

Amphetamine derivatives are used worldwide legally or illegally and intoxications may be accompanied by cardiac arrhythmias. Here, we tested contractile effects of cumulative applied (±)-amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine), and cathinone in electrically stimulated (1 Hz) human right atrial preparations (HAP) and mouse left atrial preparations and in spontaneously beating mouse right atrial preparations. In mouse atrial preparations, amphetamine increased force of contraction and beating rate in a concentration- and time-dependent manner, starting at 1 µM in left atrial preparations to 157.1% ± 3.0% and right atrial preparations to 146.6% ± 9.8% at 10 µM, respectively [mean ± standard error of the mean (SEM); n = 5; P < 0.05]. Pseudoephedrine, cathine, or cathinone alone were ineffective in mouse atrial preparations but after pre-incubation with the phosphodiesterase IV inhibitor rolipram (0.1 µM), a positive inotropic effect was noted (mean ± SEM: pseudoephedrine: 112.3% ± 9.8%; cathine: 109.0% ± 4.3%; cathinone: 138.3% ± 21.2%). The effects of all drugs were greatly attenuated by 10 µM cocaine or 10 µM propranolol treatments. However, In HAP, not only amphetamine (to a mean ± SEM of 208% ± 32%) but also pseudoephedrine (to a mean ± SEM of 287% ± 60%), cathine (to a mean ± SEM of 234% ± 52%), and cathinone (to a mean ± SEM of 217% ± 65%) increased force of contraction without the need of phosphodiesterase inhibition. The contractile effects in HAP were attenuated by 10 µM cocaine and antagonized by 10 µM propranolol. We conclude that amphetamine, pseudoephedrine, cathine, and cathinone act probably via release of noradrenaline from cardiac stores as indirect sympathomimetic agents in mouse and more pronounced in human atrial preparations.
Correlation Between N-Demethyl Imatinib Trough Concentration and Serious Adverse Reactions in Patients with Gastrointestinal Stromal Tumors: A Retrospective Cohort Study
Authors: Liu Mingfeng , Guo Teng , Ma Zhixue , Du Liying , Hou Juan , Tian Yuan , Meng Meng , Chen Xinran
Published: January 2024

Background:

Imatinib is the first-line treatment for gastrointestinal stromal tumors; however, the clinical prognosis and adverse reactions of patients vary owing to individualized discrepancies in plasma exposure.

Methods:

To determine the safe interval for steady-state plasma trough concentrations (Cmin) of imatinib and its active metabolite, N-demethyl imatinib (NDI), 328 plasma samples from 273 patients treated with imatinib were retrospectively analyzed. Imatinib Cmin and NDI Cmin were tested, and adverse reactions were recorded. The association between imatinib Cmin, NDI Cmin, and serious adverse reactions was evaluated.

Results:

The Cmin range of imatinib was 209.5–4950.0 ng/mL, with the mean value and SD of 1491.8 ± 731.4 ng/mL. The Cmin range of NDI was 80.0–2390.0 ng/mL with the mean value and SD of 610.8 ± 281.5 ng/mL. NDI Cmin was positively correlated with imatinib Cmin, whereas the ratio of NDI Cmin to imatinib Cmin (NDI Cmin/imatinib Cmin) was negatively correlated with imatinib Cmin. Univariate logistic regression analysis demonstrated that the treatment objective, daily dose, imatinib Cmin, NDI Cmin, and imatinib Cmin + NDI Cmin were significantly associated with serious adverse reactions. Multivariate logistic regression analysis showed that NDI Cmin was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL.

Conclusions:

NDI Cmin was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. Monitoring NDI Cmin was beneficial for the rational application of imatinib and individualized treatment of patients with gastrointestinal stromal tumors.
A randomized study of ceftriaxone for the prevention of infections in hospitalized patients with advanced cirrhosis
Authors: Fricker Zachary , Jiang Gordon , Patel Het , McLaughlin Annabel , Izunza Barba Sofia , Niezen Sebastian , Curry Michael
Published: January 2024

Background:

Infections frequently complicate hospital admission among patients with cirrhosis and are associated with adverse outcomes. In specific settings, administration of prophylactic antibiotics has been shown to improve outcomes. In this pilot study, we aimed to assess the feasibility of a randomized study of whether prophylactic ceftriaxone (CTX), administered to hospitalized patients with advanced cirrhosis (Model for End-Stage Liver Disease-Sodium ≥ 18) without known infection, could reduce the incidence of infection. We also sought to determine whether we could identify patients most likely to benefit through the use of clinical and laboratory parameters.

Methods:

Hospitalized patients with cirrhosis, with Model for End-Stage Liver Disease-Sodium ≥ 18 and no known infection after evaluation, were randomly assigned in a double-blinded fashion to receive either CTX 1 gr/day or placebo for up to 7 days. Subjects were monitored for incident infection and other outcomes of interest, including adverse reactions such as the development of C. difficile infection. Biomarkers of interest, including C-reactive protein and procalcitonin, were measured before initiation of treatment.

Results:

Thirty subjects were enrolled and received CTX or placebo (15 subjects each) per protocol. There were no observed statistically significant differences between groups in incidence of infection, mortality, length of stay, or key laboratory parameters, including C-reactive protein and procalcitonin. Adverse events related to treatment were rare and clinically of minor significance.

Conclusions:

Overall, enrollment of subjects proved feasible, and results from this pilot study, while inadequate for confirmation of the potential efficacy of CTX, provide evidence of study feasibility for future, more definitive clinical trials.
Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients
Authors: Luan Chih-Hsuan , Su Pin-Shuo , Chu Chi-Jen , Lin Chung-Chi , Su Chien-Wei , Luo Jiing-Chyuan , Lee I-Cheng , Chi Chen-Ta , Lee Shou-Dong , Wang Yuan-Jen , Lee Fa-Yauh , Huang Yi-Hsiang , Hou Ming-Chih
Published: January 2024

Background:

The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence.

Methods:

Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models.

Results:

The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR12), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors.

Conclusion:

This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR12, posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes.
Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors
Authors: Tonna Joseph E. , Boonstra Philip S. , MacLaren Graeme , Paden Matthew , Brodie Daniel , Anders Marc , Hoskote Aparna , Ramanathan Kollengode , Hyslop Rob , Fanning Jeffrey J. , Rycus Peter , Stead Christine , Barrett Nicholas A. , Mueller Thomas , Gómez Rene D. , Malhotra Kapoor Poonam , Fraser John F. , Bartlett Robert H. , Alexander Peta M.A. , Barbaro Ryan P. ,   on behalf of the Extracorporeal Life Support Organization (ELSO) Member Centers Group
Published: January 2024

The Extracorporeal Life Support Organization (ELSO) maintains the world’s largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0–28 days), children (29 days–17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.
Sex Disparities in Left Ventricular Assist Device Implantation: Delayed Presentation and Worse Right Heart Failure
Authors: Lamba Harveen K. , Kherallah Riyad , Nair Ajith P. , Shafii Alexis E. , Loor Gabriel , Kassi Mahwash , Chatterjee Subhasis , Rogers Joseph G. , Civitello Andrew B. , Liao Kenneth K.
Published: January 2024

We explored whether women undergo continuous-flow left ventricular assist device (CF-LVAD) implantation in later stages of heart failure (HF) than men, evidenced by worse preoperative right HF (RHF). We also compared two propensity models with and without preoperative RHF to assess its effect on outcomes. INTERMACS was queried from July 2008 to December 2017. Propensity model 1 matched men and women on age ≥50 years, HF etiology, body surface area, INTERMACS class, comorbidities, device strategy, temporary mechanical circulatory support, and device type. Model 2 included these variables plus LV end-diastolic diameter, right atrial pressure/pulmonary capillary wedge pressure, pulmonary artery pulsatility index, and right ventricular ejection fraction. The primary outcome was all-cause mortality. Secondary outcomes comprise RHF, rehospitalization, renal dysfunction, stroke, and device malfunction. In model 1, characteristics were comparable between 3,195 women and 3,195 men, except women more often had preoperative RHF and postoperative right VAD support and had worse 1 year and overall survival. In model 2, after propensity matching for additional risk factors for preoperative RHF, 1,119 women and 1,119 men had comparable post-LVAD implant RVAD use and survival. These findings suggest that women present more often with biventricular failure and after implantation have higher RHF and mortality rates.
Novel Left Ventricular Unloading Strategies in Patients on Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support
Authors: Inglis Sara S. , Rosenbaum Andrew N. , Rizzo Skylar A. , Anderson Jason H. , Yalamuri Suraj , Spencer Philip J. , Villavicencio Mauricio A. , Behfar Atta
Published: January 2024

The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP (p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO.
Perioperative hemostasis management in patients with von Willebrand disease: an institutional experience
Authors: Toenges Rosa , Miesbach Wolfgang , Ludwig Kaja , Krammer-Steiner Beate
Published: January 2024

Objectives

Patients with von Willebrand disease (vWD) undergoing surgery are routinely treated with von Willebrand factor (vWF)/factor VIII (FVIII) concentrate to control bleeding risk, but consensus is lacking on optimal dosing. This study aimed to evaluate the efficacy and safety of tailored doses of vWF/FVIII concentrate according to intervention-associated bleeding risk in vWD patients undergoing surgery.

Methods

This was a retrospective analysis of vWD patients who underwent surgical procedures at a haemophilia centre. Patients received vWF/FVIII concentrate with dosage and duration of treatment dependent on intervention type (dental, gynaecological, abdominal or orthopaedic/traumatic) and bleeding risk (moderate/high).

Results

Eighty-three surgical procedures (42 patients) were included. Median preoperative loading doses of vWF/FVIII concentrate were 29.9 IU/kg and 35.7 IU/kg for interventions with moderate (n = 16) or high (n = 67) bleeding risk, respectively. The median perioperative dose was highest in orthopaedic or trauma-related surgery (140 IU/kg) and lowest in dental or gynaecological interventions (76.4 IU/kg and 80.0 IU/kg, respectively). During follow-up, no bleeding or other complications were observed in 95% of patients.

Conclusions

Individually tailored doses of vWF/FVIII concentrate according to intervention-associated bleeding risk were effective in preventing postoperative bleeding, with few complications observed. These doses may be used as guidance in routine clinical care.
Systemic immune inflammation index and its implication on in-stent restenosis among patients with acute coronary syndrome
Authors: Ösken Altuğ , Polat Fuat , Çakir Bilal , Zengin Ahmet , Çalik Ali Nazmi , Ünal Dayi Şennur , Çam Neşe
Published: January 2024

Objective

This study aims to assess the predictive value of the Systemic Immune Inflammation Index (SII) in determining in-stent restenosis (ISR) likelihood in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI).

Methods

The study enrolled 903 ACS patients undergoing PCI, categorized into ISR (+) and ISR (−) groups based on control coronary angiography results. Demographic, clinical, laboratory, and angiographic-procedural characteristics were systematically compared.

Results

The ISR (+) group encompassed 264 individuals (29.2%), while the ISR (−) group comprised 639 individuals (70.8%). Patients had a mean age of 55.8 ± 10.2 years, with 69% being male. The ISR (+) group had higher diabetes and smoking prevalence and notably larger stent dimensions. Lab parameters showed significantly elevated creatinine, total cholesterol, red cell distribution width, white blood cell and neutrophil counts, SII index and C-reactive protein (CRP) in the ISR (+) group, while lymphocyte levels were lower. Binary logistic regression identified stent diameter (odds ratio [OR]: 0.598, 95% confidence interval [CI]: 0.383–0.935; P = 0.024), stent length (OR: 1.166, 95% CI: 1.132–1.200; P < 0.001), creatinine (OR: 0.366, 95% CI: 0.166–0.771; P = 0.003), CRP (OR: 1.075, 95% CI: 1.042–1.110; P = 0.031), and SII index (OR: 1.014, 95% CI: 1.001–1.023; P < 0.001) as independent ISR predictors.

Conclusion

The SII index exhibits potential as a predictive marker for ISR in ACS patients post-PCI, indicating systemic inflammation and heightened restenosis risk. Integrating the SII index into risk models could identify high-risk patients for targeted interventions.
Updating the Chronic Illness and Disability Payment System
Authors: Gilmer Todd , Kronick Richard
Published: January 2024

Background:

Of the 38 Medicaid programs that risk adjust payments to Medicaid managed care organizations (MCOs), 33 of them use the Chronic Illness and Disability Payment System (CDPS). There has been recent interest in adding social determinants of health (SDH) into risk-adjustment models.

Objective:

To update the CDPS models using recent MCO data based on the International Classification of Diseases version 10 coding system and to explore whether indicators of SDH are predictive of expenditures.

Research Design:

Data from 3 national Medicaid MCOs and 8 states are used to update the CDPS model. We test whether spending on Medicaid beneficiaries living in economically and socially deprived communities is greater than spending on similar beneficiaries in less deprived communities.

Subjects:

Medicaid beneficiaries with full benefits and without dual eligibility under Medicare enrolled in Medicaid MCOs in 8 states during 2017–2019, including 1.4M disabled beneficiaries, 9.2M children, and 6.4M adults.

Measures:

Health care eligibility and claims records. Indicators based on the Social Deprivation Index were used to measure SDH.

Results:

The revised CDPS model has 52 CDPS categories within 19 major categories. Six major categories of CDPS were revised: Psychiatric, Pulmonary, Renal, Cancer, Infectious Disease, and Hematological. We found no relationship between health care spending and the Social Deprivation Index.

Conclusions:

The revised CDPS models and regression weights reflect the updated International Classification of Diseases-10 coding system and recent managed care delivery. States should choose alternative payment strategies to address disparities in health and health outcomes.
Artificial Intelligence-Enabled Prostate Cancer Diagnosis and Prognosis: Current State and Future Implications
Authors: Satturwar Swati , Parwani Anil V.
Published: January 2024

In this modern era of digital pathology, artificial intelligence (AI)-based diagnostics for prostate cancer has become a hot topic. Multiple retrospective studies have demonstrated the benefits of AI-based diagnostic solutions for prostate cancer that includes improved prostate cancer detection, quantification, grading, interobserver concordance, cost and time savings, and a potential to reduce pathologists’ workload and enhance pathology laboratory workflow. One of the major milestones is the Food and Drug Administration approval of Paige prostate AI for a second review of prostate cancer diagnosed using core needle biopsies. However, implementation of these AI tools for routine prostate cancer diagnostics is still lacking. Some of the limiting factors include costly digital pathology workflow, lack of regulatory guidelines for deployment of AI, and lack of prospective studies demonstrating the actual benefits of AI algorithms. Apart from diagnosis, AI algorithms have the potential to uncover novel insights into understanding the biology of prostate cancer and enable better risk stratification, and prognostication. This article includes an in-depth review of the current state of AI for prostate cancer diagnosis and highlights the future prospects of AI in prostate pathology for improved patient care.
Triangulation of Routine Antenatal HIV Prevalence Data and Adjusted HIV Estimates in Mozambique
Authors: Stevens Oliver , Boothe Makini , Tiberi Orrin , Mahy Mary , Walker Patrick , Glaubius Robert , McOwen Jordan , Couto Aleny , Cunha Morais , Imai-Eaton Jeffrey W.
Published: January 2024

Background:

Routine health system data are central to monitoring HIV trends. In Mozambique, the reported number of women receiving antenatal care (ANC) and antiretroviral therapy for prevention of mother-to-child transmission (PMTCT) has exceeded the Spectrum-estimated number of pregnant women since 2017. In some provinces, reported HIV prevalence in pregnant women has declined faster than epidemiologically plausible. We hypothesized that these issues are linked and caused by programmatic overenumeration of HIV-negative pregnant women at ANC.

Methods:

We triangulated program-reported ANC client numbers with survey-based fertility estimates and facility birth data adjusted for the proportion of facility births. We used survey-reported ANC attendance to produce adjusted time series of HIV prevalence in pregnant women, adjusted for hypothesized program double counting. We calibrated the Spectrum HIV estimation models to adjusted HIV prevalence data to produce adjusted adult and pediatric HIV estimates.

Results:

ANC client numbers were not consistent with facility birth data or modeled population estimates indicating ANC data quality issues in all provinces. Adjusted provincial ANC HIV prevalence in 2021 was median 45% [interquartile range 35%–52% or 2.3 percentage points (interquartile range 2.5–3.5)] higher than reported HIV prevalence. In 2021, calibrating to adjusted antenatal HIV prevalence lowered PMTCT coverage to less than 100% in most provinces and increased the modeled number of new child infections by 35%. The adjusted results better reconciled adult and pediatric antiretroviral treatment coverage and antenatal HIV prevalence with regional fertility estimates.

Conclusions:

Adjusting HIV prevalence in pregnant women using nationally representative household survey data on ANC attendance produced estimates more consistent with surveillance data. The number of children living with HIV in Mozambique has been substantially underestimated because of biased routine ANC prevalence. Renewed focus on HIV surveillance among pregnant women would improve PMTCT coverage and pediatric HIV estimates.
New HIV Infections Among Key Populations and Their Partners in 2010 and 2022, by World Region: A Multisources Estimation
Authors: Korenromp Eline L. , Sabin Keith , Stover John , Brown Tim , Johnson Leigh F. , Martin-Hughes Rowan , ten Brink Debra , Teng Yu , Stevens Oliver , Silhol Romain , Arias-Garcia Sonia , Kimani Joshua , Glaubius Robert , Vickerman Peter , Mahy Mary
Published: January 2024

Background:

Previously, The Joint United Nations Programme on HIV/AIDS estimated proportions of adult new HIV infections among key populations (KPs) in the last calendar year, globally and in 8 regions. We refined and updated these, for 2010 and 2022, using country-level trend models informed by national data.

Methods:

Infections among 15–49 year olds were estimated for sex workers (SWs), male clients of female SW, men who have sex with men (MSM), people who inject drugs (PWID), transgender women (TGW), and non-KP sex partners of these groups. Transmission models used were Goals (71 countries), AIDS Epidemic Model (13 Asian countries), Optima (9 European and Central Asian countries), and Thembisa (South Africa). Statistical Estimation and Projection Package fits were used for 15 countries. For 40 countries, new infections in 1 or more KPs were approximated from first-time diagnoses by the mode of transmission. Infection proportions among nonclient partners came from Goals, Optima, AIDS Epidemic Model, and Thembisa. For remaining countries and groups not represented in models, median proportions by KP were extrapolated from countries modeled within the same region.

Results:

Across 172 countries, estimated proportions of new adult infections in 2010 and 2022 were both 7.7% for SW, 11% and 20% for MSM, 0.72% and 1.1% for TGW, 6.8% and 8.0% for PWID, 12% and 10% for clients, and 5.3% and 8.2% for nonclient partners. In sub-Saharan Africa, proportions of new HIV infections decreased among SW, clients, and non-KP partners but increased for PWID; elsewhere these groups' 2010-to-2022 differences were opposite. For MSM and TGW, the proportions increased across all regions.

Conclusions:

KPs continue to have disproportionately high HIV incidence.