Salvage Reconstruction of Composite Defects of the Anterior Mandible, Floor of Mouth, and Lip.

Anterior mandible defects result in loss of support for the tongue, floor of the mouth and lower lip, resulting in impairment of airway, feeding, and speech. We treated four patients with these "Andy Gump" deformities. Reconstruction was performed with two free flaps: a fibula osteocutaneous flap for the anterior mandible and floor of the mouth, and a soft tissue free flap for the lip, chin, and anterior neck. The lower lip was suspended cranially with fascia or tendon grafts ± mini-temporalis turndown flaps. All flaps survived completely. All patients were tube feed-dependent before surgery; they all resumed an oral diet. All tracheostomies were decannulated. Lip competence was restored as evidenced by cessation of drooling. Speech improved from unintelligible to intelligible with frequent repetitions. Objective assessment was performed with the functional intraoral Glasgow scale; the mean FIGS score improved from 3.25 (range 3-4) to 11 (range 9-13). We conclude that composite anterior mandible and tongue defects have large tissue requirements that require multiple free flaps. Reconstruction leads to significant improvement in function.

Mastering Quality: Uniting Risk Assessment With Quality by Design (QbD) Principles for Pharmaceutical Excellence.

The aim of this article is to present ideas and tools of risk assessment that can be implemented to overcome various pharmaceutical quality challenges. These elements cover the development, production, distribution, inspection, and reporting of review procedures for drug substances, drug products, and biological products at every stage of their lifecycle. In light of the constant requirement to ensure the drug's efficacy, safety, and quality, the pharmaceutical sector is always evolving. A key strategy for attaining pharmaceutical excellence in this dynamic environment is incorporating novel methods like quality by design (QbD) and risk assessment. Risk assessment is a methodical strategy to locate, assess, and minimize any risks in the manufacturing and development of pharmaceuticals. On the other hand, QbD principles place more emphasis on end-product testing and place it in the context of designing quality into the product from the beginning. The major goal of this paper is to address and examine the integration of risk assessment approaches with the QbD principle workflow to ensure pharmaceutical quality. Recent articles on how risk assessment has been used in pharmaceuticals were evaluated. To provide a useful overview, the various assessment methodologies have been highlighted, emphasizing their benefits and drawbacks.

Multidrug-Resistant Shigellosis as a Sexually Transmitted Infection in Advanced HIV: A Case Report.

Shigellosis, a significant public health concern, has increasingly been recognized as a sexually transmitted infection (STI) among men who have sex with men (MSM), particularly in those with HIV. This case report describes a 25-year-old MSM with advanced HIV who presented with recurrent multidrug-resistant (MDR) Shigella flexneri infection despite multiple hospitalizations and antibiotic courses. The patient's high-risk sexual behaviors and suboptimal HIV management likely contributed to recurrent exposure to Shigella and the selection of resistant strains. This case highlights the complex interplay of individual behaviors, immune suppression, antimicrobial resistance, and the healthcare system in the context of this emerging STI. It underscores the importance of optimized HIV care, comprehensive patient education, robust healthcare coordination, and strengthened surveillance to effectively combat MDR shigellosis in vulnerable populations.

When to feed after percutaneous endoscopic gastrostomy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Initiation of feeding after percutaneous endoscopic gastrostomy (PEG) placement has been debated. Randomized controlled trials (RCTs) have been performed on early feeding compared with delayed feeding after PEG placement with varying results. Therefore, a meta-analysis was conducted examining early vs delayed feeding after placement of a PEG. METHODS: A comprehensive search of databases was conducted in January 2024. Peer-reviewed published RCTs comparing early feeding (≤4 h) with delayed feeding (>4 h) were identified and included in the meta-analysis. Meta-analysis was completed using pooled estimates of overall complications, individual complications, mortality ≤72 h, and number of day 1 significant gastric residual volumes. RESULTS: Six RCTs (n = 467) were included in the analysis. Comparison of early feeding with delayed feeding after PEG showed no statistically significant differences for overall complications (P = 0.18), mortality ≤72 h (P = 0.3), and number of day 1 significant gastric residual volumes (P = 0.05). No differences were also noted for individual complications, including vomiting, wound infection, bleeding, or diarrhea. CONCLUSION: Feeding ≤4 h after PEG have no differences in minor and major complications compared with that of delayed feeding. Early feeding ≤4 h is safe and should be recommended in future guidelines.

System-based strategies for mitigating burnout in radiology.

BACKGROUND: Burnout is a chronic problem prevalent in radiology, with a significant burden on individuals and healthcare systems. DISCUSSION: A substantial portion of the literature on managing burnout has focused on individual-based remedies. We posit that burnout is a systemic problem and present an overview of some system-based strategies that could be employed to mitigate burnout in radiology. These include managing workload, optimizing work shifts, maximizing autonomy, limiting work-life conflicts, creating opportunities for professional fulfillment, utilizing user-friendly electronic medical records (EMR), deploying efficient picture archiving and communication systems (PACS), building system redundancy, leadership transparency, and fostering a healthy work environment.  CONCLUSION: System-based strategies can help mitigate burnout.

Long-Term Biodegradation of Polyacrylamide Gel Residues in Mammary Glands: Physico-Chemical Analysis, Chromatographic Detection, and Implications for Chronic Inflammation.

In the past, polyacrylamide hydrogel was a popular choice for breast augmentation filler, and many women underwent mammoplasty with this gel. However, due to frequent complications, the use of polyacrylamide hydrogel in mammoplasty has been banned. Despite this ban, patients experiencing complications still seek medical treatment. The aim of this study was to investigate the fate of the polymer over a defined implantation period. Biopsies of breast implants were obtained from patients with 23 and 27 years of post-mammoplasty. These biopsies were meticulously purified from biological impurities and subjected to analysis using IR spectrometry, liquid chromatography-mass spectrometry, gas chromatography, and differential scanning calorimetry. The findings revealed the presence of polyacrylamide hydrogel residues, along with degradation products, within the infected material. Notably, the low-molecular-weight degradation products revealed via gas chromatography are aggressive and toxic substances capable of inducing chronic inflammation. This study sheds light on the long-term consequences of polyacrylamide hydrogel implantation, highlighting the persistence of harmful degradation products and their role in exacerbating patient complications.

Thermoelectric Properties of CrS2-x Te x (x: 0, 1, 2) Dichalcogenides Monolayers: First-Principles Study.

In this study, we conducted first-principles calculations interfaced with Boltzmann transport theory to examine the carrier-dependent thermoelectric properties of CrS2-x Te x (x: 0, 1, 2) dichalcogenides monolayers. We conducted a systematic analysis of the structural, phonon band structures, elastic properties, electronic structures, and thermoelectric properties, of electron (e) and hole (h) doped CrS2-x Te x (x: 0, 1, 2) dichalcogenides monolayers. The studied 2D TMDCs exhibit structural stability, as indicated by the negative formation energy. Additionally, the phonon band structures indicate no negative frequencies along any wave vector, confirming the dynamic stability of the CrS2-x Te x monolayers. CrS2 and CrTe2 monolayers are semiconductors with direct bandgaps of 1.01 and 0.67 eV, respectively. A Janus CrSTe monolayer has a smaller bandgap of 0.21 eV. Temperatures range between 300 and 500 K, and concentrations of e(h) doped in the range of 1.0 × 1018-1.0 × 1020 cm-3 are used to compute the thermoelectric transport coefficients. The low lattice thermal conductivity is predicted for the studied compounds, among which Janus CrSTe and CrTe2 have the minimum value of κlat ≈ 1 W/mK @ 700 K. The figure-of-merit ZT projected value at the optimal e(h) doping concentration for the CrS2 monolayer is as high as 0.07 (0.09) at 500 K. Our findings demonstrate how to design improved thermoelectric materials suitable for various thermoelectric devices.

Prevalence and predictors of mitral annular disjunction and ventricular ectopy in mitral valve prolapse.

BACKGROUND: Mitral annular disjunction (MAD) is associated with ventricular arrhythmia in mitral valve prolapse (MVP). The proportional risk from MAD and other predictors of ventricular arrhythmia in MVP has not been well characterized. OBJECTIVE: This study aimed to identify predictors of complex or frequent ventricular ectopy (cfVE) in MVP and to quantify risk of cfVE and mortality in MVP with MAD. METHODS: We studied 632 adult patients with MVP on transthoracic echocardiography at the University of North Carolina Medical Center from 2016 to 2019 (median age, 64 [interquartile range, 52-74] years; 52.7% female; 16.3% African American). Resting and ambulatory electrocardiograms were used to identify cfVE. RESULTS: MAD was present in 94 (14.9%) patients. Independent associations of MAD were bileaflet prolapse (odds ratio [95% CI], 4.25 [2.47-7.33]; P < .0001), myxomatous valve (2.17 [1.27-3.71]; P = .005), absence of hypertension (2.00 [1.21-3.32]; P = .007), electrocardiogram inferior or lateral lead T-wave inversion (2.07 [1.23-3.48]; P = .006), and female sex (1.99 [1.21-3.25]; P = .006). cfVE was frequent with MAD (39 [41.5%] vs 93 [17.3%] without; P < .0001). Independent cfVE predictors were MAD (hazard ratio [95% CI], 2.23 [1.47-3.36]; P = .0001), bileaflet prolapse (1.86 [1.25-2.76]; P = .002), heart failure (1.79 [1.16-2.77]; P = .009), lower left ventricular ejection fraction (0.14 [0.03-0.61]; P = .009), coronary artery disease (1.60 [1.05-2.43]; P = .03), and inferior or lateral lead T-wave inversion (1.51 [1.03-2.22]; P = .03). After a median of 40 (33-48) months, there was increased mortality with MAD (P = .04). CONCLUSION: MAD in MVP is associated with bileaflet or myxomatous MVP, absence of hypertension, T-wave inversion, and female sex. There is increased cfVE and mortality with MAD, highlighting the need for closer follow-up of these patients.

Cryptic diversity in southern African kelp.

The southern coast of Africa is one of the few places in the world where water temperatures are predicted to cool in the future. This endemism-rich coastline is home to two sister species of kelps of the genus Ecklonia maxima and Ecklonia radiata, each associated with specific thermal niches, and occuring primarily on opposite sides of the southern tip of Africa. Historical distribution records indicate that E. maxima has recently shifted its distribution ~ 70 km eastward, to sites where only E. radiata was previously reported. The contact of sister species with contrasting thermal affinities and the occurrence of mixed morphologies raised the hypothesis that hybridization might be occurring in this contact zone. Here we describe the genetic structure of the genus Ecklonia along the southern coast of Africa and investigate potential hybridization and cryptic diversity using a combination of nuclear microsatellites and mitochondrial markers. We found that both species have geographically discrete genetic clusters, consistent with expected phylogeographic breaks along this coastline. In addition, depth-isolated populations were found to harbor unique genetic diversity, including a third Ecklonia lineage. Mito-nuclear discordance and high genetic divergence in the contact zones suggest multiple hybridization events between Ecklonia species. Discordance between morphological and molecular identification suggests the potential influence of abiotic factors leading to convergent phenotypes in the contact zones. Our results highlight an example of cryptic diversity and hybridization driven by contact between two closely related keystone species with contrasting thermal affinities.

Design of overnight radiology shifts - primum non nocere.

Overnight radiology (ONR) is necessary for providing timely patient care but poses unique professional and personal challenges to the radiologists. Maintaining a sustainable, long-term overnight radiology program hinges on the retention of radiologists who grasp the institutional workflow and can adeptly navigate inherent disruptions while consistently delivering high-quality patient care. Design of radiology shifts can significantly impact the performance and well-being of radiologists, with downstream implications for patient care and risk management. We provide a narrative review of literature to make recommendations for optimally designing ONR shifts, with a focus on professional and personal challenges pertinent to overnight radiologists and system-based risk mitigation strategies.

Natural history of clinical outcomes and hepatic decompensation in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The natural progression of hepatic decompensation in metabolic dysfunction-associated steatotic liver disease (MASLD) is not well-characterised. We aimed to describe it by conducting a retrospective analysis. METHODS: This longitudinal, retrospective analysis of well-characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver-related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured. RESULTS: Of the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow-up of 3.2 years. Ascites was the most common first liver-related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver-related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy-three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years. CONCLUSION: The most common first liver-related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.

Complex percutaneous coronary intervention in patients unable to undergo coronary artery bypass grafting during the COVID-19 pandemic: insights from the UK-ReVasc Registry.

OBJECTIVES: Cardiac surgery for coronary artery disease was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with disease ordinarily treated with coronary artery bypass grafting (CABG) instead underwent percutaneous coronary intervention (PCI). We sought to describe 12-month outcomes following PCI in patients who would typically have undergone CABG. METHODS: Between March 1 and July 31, 2020, patients who received revascularization with PCI when CABG would have been the primary choice of revascularization were enrolled in the prospective, multicenter UK-ReVasc Registry. We evaluated the following major adverse cardiovascular events at 12 months: all-cause mortality, myocardial infarction, repeat revascularization, stroke, major bleeding, and stent thrombosis. RESULTS: A total of 215 patients were enrolled across 45 PCI centers in the United Kingdom. Twelve-month follow up data were obtained for 97% of the cases. There were 9 deaths (4.3%), 5 myocardial infarctions (2.4%), 12 repeat revascularizations (5.7%), 1 stroke (0.5%), 3 major bleeds (1.4%), and no cases of stent thrombosis. No difference in the primary endpoint was observed between patients who received complete vs incomplete revascularization (residual SYNTAX score £ 8 vs > 8) (P = .22). CONCLUSIONS: In patients with patterns of coronary disease in whom CABG would have been the primary therapeutic choice outside of the pandemic, PCI was associated with acceptable outcomes at 12 months of follow-up. Contemporary randomized trials that compare PCI to CABG in such patient cohorts may be warranted.

A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.

The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.

Low liver fat in non-alcoholic steatohepatitis-related significant fibrosis and cirrhosis is associated with hepatocellular carcinoma, decompensation and mortality.

BACKGROUND: Progression to cirrhosis in non-alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH-related significant fibrosis and cirrhosis is unclear. AIM: To investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH-related significant fibrosis and cirrhosis. METHODS: In this meta-analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI-derived protein density fat fraction (MRI-PDFF) were enrolled, and 296 patients with longitudinal follow-up were analysed. MRE combined with fibrosis-4 (MEFIB-index), and MRI-PDFF were used to measure liver fibrosis and fat, respectively. MEFIB-negative, MEFIB-positive+ MRI-PDFF ≥5% and MEFIB-positive+ MRI-PDFF <5% were defined as no significant liver fibrosis, NASH with significant fibrosis and higher liver fat content, and NASH with significant fibrosis and low liver fat content groups, respectively. The primary outcome was hepatic decompensation, HCC and death. RESULTS: The rates of decompensation, HCC and mortality were highest in the NASH with significant fibrosis and low liver fat group (33%, 17% and 17%, respectively), followed by the NASH with significant fibrosis and higher liver fat group (18%, 13% and 13% respectively), and lowest in the no significant fibrosis (MEFIB-negative) group (0%, 1% and 2% respectively). In multivariable-adjusted analysis, low liver fat content was strongly associated (HR = 42.2 [95% CI: 7.5-235.5, p < 0.0001]) with HCC, decompensation and death. Sensitivity analyses for patients with cirrhosis (MRE ≥5 kPa) determined consistent findings. CONCLUSIONS: Low liver fat content in patients with burnt-out NASH-related significant fibrosis and cirrhosis is associated with an increase in hepatic decompensation, HCC and mortality.

Genomic analysis of wolves from Pakistan clarifies boundaries among three divergent wolf lineages.

Among the three main divergent lineages of gray wolf (Canis lupus), the Holarctic lineage is the most widespread and best-studied, particularly in North America and Europe. Less is known about Tibetan (also called Himalayan) and Indian wolf lineages in southern Asia, especially in areas surrounding Pakistan where all three lineages are thought to meet. Given the endangered status of the Indian wolf in neighboring India and unclear southwestern boundary of the Tibetan wolf range, we conducted mitochondrial and genome-wide sequencing of wolves from Pakistan and Kyrgyzstan. Sequences of the mitochondrial D-loop region of 81 wolves from Pakistan indicated contact zones between Holarctic and Indian lineages across the northern and western mountains of Pakistan. Reduced-representation genome sequencing of 8 wolves indicated an east-to-west cline of Indian to Holarctic ancestry, consistent with a contact zone between these two lineages in Pakistan. The western boundary of the Tibetan lineage corresponded to the Ladakh region of India's Himalayas with a narrow zone of admixture spanning this boundary from the Karakoram Mountains of northern Pakistan into Ladakh, India. Our results highlight the conservation significance of Pakistan's wolf populations, especially the remaining populations in Sindh and Southern Punjab that represent the highly endangered Indian lineage.

Using Science and Technology to Unveil The Hidden Delicacy Terfezia arenaria, a Desert Truffle.

Terfezia arenaria is a desert truffle native to the Mediterranean Basin region, highly appreciated for its nutritional and aromatic properties. Despite the increasing interest in this desert truffle, T. arenaria is not listed as an edible truffle authorized for trade in the European Union. Therefore, our objective was to showcase T. arenaria's nutritional and chemical composition and volatile profile. The nutritional analysis showed that T. arenaria is a good source of carbohydrates (67%), proteins (14%), and dietary fibre (10%), resulting in a Nutri-Score A. The truffle's volatile profile was dominated by eight-carbon volatile compounds, with 1-octen-3-ol being the most abundant (64%), and 29 compounds were reported for the first time for T. arenaria. T. arenaria's nutritional and chemical compositions were similar to those of four commercial mushroom and truffle species, while the aromatic profile was not. An electronic nose corroborated that T. arenaria's aromatic profile differs from that of the other four tested mushroom and truffle species. Our data showed that T. arenaria is a valuable food resource with a unique aroma and an analogous composition to meat, which makes it an ideal source for plant-based meat products. Our findings could help promote a sustainable future exploitation of T. arenaria and ensure the quality and authenticity of this delicacy.

Shaping global vaccine acceptance with localized knowledge: a report from the inaugural VARN2022 conference.

The first conference of the Vaccination Acceptance Research Network, VARN2022: Shaping Global Vaccine Acceptance with Localized Knowledge, was held virtually, from March 1st to 3rd 2022. This inaugural event brought together a global representation of experts to discuss key priorities and opportunities emerging across the ecosystem of vaccine acceptance and demand, from policies to programs and practice. Convened by the Sabin Vaccine Institute, VARN aims to support dialogue among multidisciplinary stakeholders to enhance the uptake of social and behavioral science-based solutions for vaccination decision-makers and implementers. The conference centered around four key themes: 1) Understanding vaccine acceptance and its drivers; 2) One size does not fit all: community- and context-specific approaches to increase vaccine acceptance and demand; 3) Fighting the infodemic and harnessing social media for good; and 4) Frameworks, data integrity and evaluation of best practices. Across the conference, presenters and participants considered the drivers of and strategies to increase vaccine acceptance and demand relating to COVID-19 vaccination and other vaccines across the life-course and across low-, middle- and high-income settings. VARN2022 provided a wealth of evidence from around the world, highlighting the need for human-centered, multi-sectoral and transdisciplinary approaches to improve vaccine acceptance and demand. This report summarizes insights from the diverse presentations and discussions held at VARN2022, which will form a roadmap for future research, policy making, and interventions to improve vaccine acceptance and demand globally.

MEFIB-Index and MAST-Score in the assessment of hepatic decompensation in metabolic dysfunction-associated steatosis liver disease-Individual participant data meta-analyses.

BACKGROUND: There are limited data regarding the longitudinal association between MEFIB-Index (MRE combined with FIB-4) versus MAST-Score (MRI-aspartate aminotransferase) and hepatic decompensation. AIM: To examine the longitudinal association between MEFIB-Index versus MAST-Score in predicting hepatic decompensation in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI-PDFF and were followed for hepatic decompensation. Cox-proportional hazard analyses were used to assess the association between MEFIB-Index versus MAST-Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment. RESULTS: This meta-analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB-Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST-Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow-up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB-Index [HR = 49.22 (95% CI: 6.23-388.64, p < 0.001)] and a positive MAST-Score [HR = 3.86 (95% CI: 1.46-10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB-Index (c-statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST-Score (c-statistic: 0.81, SE = 0.03) (p < 0.0001) in predicting hepatic decompensation. CONCLUSION: A combination of MRI-based biomarker and blood tests, MEFIB-Index and MAST-Score can predict the risk of hepatic decompensation in patients with MASLD.