Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

BACKGROUND AND AIMS: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking. APPROACH AND RESULTS: We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10 kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes).During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate: 0.74%/y, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12 kPa and follow-up platelet count >150 g/L) or rule-in (FU-liver stiffness measurement ≥25 kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure. CONCLUSIONS: In patients with compensated advanced chronic liver disease, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long term (>3 y). One-time post-treatment risk stratification based on noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. IMPACT AND IMPLICATIONS: Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure.

Evaluating the Effects of Corn Flour Product Consumption on Cardiometabolic Outcomes and the Gut Microbiota in Adults with Elevated Cholesterol: A Randomized Crossover.

BACKGROUND: Consumption of whole grains is associated with a reduction in chronic diseases and offers benefits for cardiovascular health and metabolic regulation. The relationship between whole-grain corn and corn bran with the gut microbiota (GM) remains an area of growing interest, particularly regarding their influence on cardiometabolic health. OBJECTIVES: To investigate the effects of different corn flours on cardiometabolic outcomes and GM changes in adults with elevated low-density lipoprotein cholesterol (LDL cholesterol) concentrations. METHODS: In this crossover study, 36 adults with LDL cholesterol above 110 mg/dL consumed 48 g/d of 3 corn flour types for 4 wk: whole-grain corn meal, refined corn meal (RCM), and a blend of RCM and corn bran (RCM + B). We assessed the impact on cardiometabolic markers [LDL cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), total cholesterol, and triglycerides)] and GM composition and estimated function. Statistical analyses included mixed-effects modeling and responder (>5% decrease in LDL cholesterol) analysis to evaluate changes in GM related to lipid profile improvements. RESULTS: Of the 3 corn flour types, only RCM + B significantly decreased LDL cholesterol over time (-10.4 ± 3.6 mg/dL, P = 0.005) and marginally decreased total cholesterol (-9.2 ± 3.9 mg/dL, P = 0.072) over time. There were no significant effects on HDL cholesterol or triglyceride concentrations. No significant changes were observed in GM alpha diversity, whereas beta diversity metrics indicated individual variability. Two genera, unclassified Lachnospiraceae and Agathobaculum (Padj ≤ 0.096), differed significantly by treatment, but only Agathobaculum remained significantly elevated in the whole-grain corn meal, compared to RCM and RCM + B, after adjustment for multiple comparisons. CONCLUSIONS: The type of corn flour, particularly RCM + B, notably influenced LDL cholesterol concentrations in adults with elevated LDL cholesterol. This study suggests that incorporating milled fractions (e.g., bran) of whole-grain corn with refined corn flour may be a viable alternative to supplementing manufactured grain products with isolated or synthetic fibers for improved metabolic health. This trial was registered at clinicaltrials.gov as NCT03967990.

Share of food group expenditure in Mexican households according to the gender of the head of household and size of the locality.

OBJECTIVE: To evaluate differences in the percentage of expenditure on food groups in Mexican households according to the gender of the household head and the size of the locality. DESIGN: Analysis of secondary data from the National Household Income and Expenditure Survey (ENIGH) 2018. We estimated the percentage of expenditure on fifteen food groups according to the gender of the head of household and locality size and evaluated the differences using a two-part model approach. SETTING: Mexico, 2018. PARTICIPANTS: A nationally representative sample of 74 647 Mexican households. RESULTS: Female-headed households allocated a lower share of expenditure to the purchase of sweetened beverages and alcoholic beverages and higher percentages to milk and dairy, fruits and water. In comparison with metropolitan households, households in rural and urban localities spent more on cereals and tubers, sugar and honey, oil and fat and less on food away from home. CONCLUSIONS: Households allocate different percentages of expenditure to diverse food groups according to the gender of the head of the household and the size of the locality where they are located. Future research should focus on understanding the economic and social disparities related to differences in food expenditure, including the gender perspective.

Time-expanded φOTDR using low-frequency electronics.

Time expanded phase-sensitive optical time-domain reflectometry (TE-φOTDR) is a recently reported technique for distributed optical fiber sensing based on the interference of two mutually coherent optical frequency combs. This approach enables distributed acoustic sensing with centimeter resolution while keeping the detection bandwidth in the megahertz range. In this paper, we demonstrate that TE-φOTDR can be realized with low-frequency electronics for both signal generation and detection. This achievement is possible thanks to the use of a couple of electro-optic comb generators driven by commercially available step recovery diodes. These components are fed by radio frequencies that are orders of magnitude lower than those involved in the signals so far originated by ultrafast waveform generation. The result is a simple, compact, low-cost and potentially field-deployable sensor that works without resorting to any decoding algorithm. Besides, high-resolution distributed sensing is carried out with no need of coding strategies or enhanced backscatter fibers. To check the capabilities of our system, we perform distributed strain sensing over a range of 20 m. The spatial resolution is 3 cm and the acoustic sampling rate can be increased up to 200 Hz. This performance reveals the prospective of the proposed approach for field applications, including structural health monitoring.

Noise analysis in direct detection and coherent detection phase-sensitive optical time-domain reflectometry systems.

This study compares noise and signal-to-noise ratio (SNR) in direct detection and coherent detection fiber-based distributed acoustic sensing (DAS) systems. Both detection schemes employ the dynamic analysis of Rayleigh-backscattered light in phase-sensitive optical time-domain reflectometry (ΦOTDR) systems. Through theoretical and experimental analysis, it is determined that for photodetection filters with a sufficiently narrow bandwidth, the SNR performance of both detection schemes is comparable. However, for filters with poor selectivity, coherent detection was found to exhibit superior performance. These findings provide crucial guidelines for the design of high-performance time-domain DAS systems.

Dynamic curvature sensing using time expanded ΦOTDR.

Shape sensing can be accomplished using optical fiber sensors through different interrogation principles such as fiber Bragg gratings, optical frequency-domain reflectometry (OFDR), or optical time-domain reflectometry (OTDR). These techniques are either not entirely distributed, have poor performance in dynamic sensing, or are only valid for few-meter-long fibers. Here, we present a system able to perform distributed curvature sensing with a range of 125 m, 10-cm resolution, and a sampling rate of 50 Hz. This is done by interrogating three cores of a multi-core fiber (MCF) with the novel, to the best of our knowledge, time-expanded phase-sensitive (TE-Φ)OTDR technique. This system fills a performance gap in fiber shape sensors, opening the door to applications in civil engineering, medicine, or seismology.

Identification and validation of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening.

Blastocystis sp. is among the most frequent intestinal protists identified in humans globally. However, characterization of Blastocystis subtype diversity in humans is ongoing. We report here the identification of novel Blastocystis subtype ST41 in a Colombian patient undergoing colorectal cancer screening involving colonoscopy and fecal testing (microscopy, culture, PCR). The full-length ssu rRNA gene sequence of the protist was generated using MinION long-read sequencing technology. The validity of the novel subtype was confirmed via phylogenetic and pairwise distance analyses of the full-length ST41 sequence and all other valid subtypes. The study provides reference material essential for conducting subsequent experimental studies.

Humidity-insensitive optical fibers for distributed sensing applications.

Humidity is a critical environmental factor in various applications, and its temperature dependence must be considered when developing thermo-hygrometer fiber sensors. The optical fibers that constitute the sensor must have a temperature reference, which should be resistant to humidity to avoid cross-sensitivities. This paper presents two innovative optical fibers insensitive to humidity over temperatures ranging from -20∘ C to 55°C. To the best of our knowledge, the novel standard size optical fibers coated with acrylate and silicone are tested under controlled conditions using an optical time-domain reflectometer sensor based on Rayleigh scattering. The sensor achieves meter-range resolution over kilometers of length with a response time of few minutes.

Determinants of tap water mistrust among Phoenix, Arizona Latinx adults.

The purpose of this investigation was to characterize factors that predict tap water mistrust among Phoenix, Arizona Latinx adults. Participants (n = 492, 28 ± 7 years, 37.4% female) completed water security experience-based scales and an Adapted Survey of Water Issues in Arizona. Binary logistic regression determined odds ratios (OR) with 95% confidence intervals (95% CI) for the odds of perceiving tap water to be unsafe. Of all participants, 51.2% perceived their tap water to be unsafe. The odds of mistrusting tap water were significantly greater for each additional favorable perception of bottled compared to tap water (e.g., tastes/smells better; OR = 1.94, 95% CI = 1.50, 2.50), negative home tap water experience (e.g., hard water mineral deposits and rusty color; OR = 1.32, 95% CI = 1.12, 1.56), use of alternatives to home tap water (OR = 1.25, 95% CI = 1.04, 1.51), and with decreased water quality and acceptability (OR = 1.21, 95% CI = 1.01, 1.45; P < 0.05). The odds of mistrusting tap water were significantly lower for those whose primary source of drinking water is the public supply (municipal) (OR = 0.07, 95% CI = 0.01, 0.63) and with decreased water access (OR = 0.56, 95% CI = 0.48, 0.66; P < 0.05). Latinx mistrust of tap water appears to be associated with organoleptic perceptions and reliance on alternatives to the home drinking water system.

Cardiometabolic Risk Factors Among Insufficiently Active African American Women With Obesity: Baseline Findings From Smart Walk.

BACKGROUND: Low moderate-to-vigorous physical activity (MVPA) levels and obesity are associated with increased cardiometabolic disease risk. OBJECTIVE: The aim of this study was to describe MVPA and cardiometabolic risk characteristics of insufficiently active African American women with obesity (N = 60) enrolled in a culturally tailored MVPA intervention. METHODS: We assessed accelerometer-measured and self-reported MVPA, blood pressure, serum lipid profiles, cardiorespiratory fitness (VO 2 peak), and aortic pulse wave velocity. RESULTS: Participants (mean age, 38.4; mean body mass index, 40.6 kg/m 2 ) averaged 15 min/d of accelerometer-measured MVPA and 30 min/wk of self-reported MVPA. Systolic and diastolic blood pressure levels were elevated (135.4 and 84.0 mm Hg, respectively). With the exception of low-density lipoprotein cholesterol (121.4 mg/dL) and high-density lipoprotein cholesterol (47.6 mg/dL), lipid profiles were within reference ranges. Compared with normative reference values, average VO 2 peak was low (18.7 mL/kg/min), and pulse wave velocity was high (7.4 m/s). CONCLUSIONS: Our sample of insufficiently active African American women with obesity was at an elevated risk for cardiometabolic disease.

Single-cell mtDNA heteroplasmy in colorectal cancer.

Human mitochondria can be genetically distinct within the same individual, a phenomenon known as heteroplasmy. In cancer, this phenomenon seems exacerbated, and most mitochondrial mutations seem to be heteroplasmic. How this genetic variation is arranged within and among normal and tumor cells is not well understood. To address this question, here we sequenced single-cell mitochondrial genomes from multiple normal and tumoral locations in four colorectal cancer patients. Our results suggest that single cells, both normal and tumoral, can carry various mitochondrial haplotypes. Remarkably, this intra-cell heteroplasmy can arise before tumor development and be maintained afterward in specific tumoral cell subpopulations. At least in the colorectal patients studied here, the somatic mutations in the single-cells do not seem to have a prominent role in tumorigenesis.

Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer.

The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using different enrichment strategies (CellSearch, Parsortix, and FACS). Mutations inferred in the CTC pools differed depending on the enrichment strategy and, in all cases, represented a subset of the mutations detected in the matched primary tumor samples. However, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures, and drug-suitability scores remarkably close to those found in matching primary tumor samples. In addition, FACS CTC pools were enriched in apparent sequencing artifacts, leading to much higher genomic diversity estimates. Our results highlight the utility of CTCs to assess the genomic heterogeneity of individual tumors and help clinicians prioritize drugs in mCRC.

AKI-HRS, more than a name change for type-1 hepatorenal syndrome.

Acute renal failure (ARF) development is likely the most relevant event in the natural history of severely decompensated cirrhosis. It is a common complication affecting 20-49% of inpatients with decompensated cirrhosis. Also, its presence is associated with a notable increase in morbidity and mortality, and hampers management of classical cirrhosis decompensations such as ascites or hepatic encephalopathy.

[Design and validation of a scale to measure nomophobia among children 9-13 years old]. / Diseño y validación de una escala para medir la nomofobia en niños de 9 a 13 años.

OBJECTIVE: To design and validate a nomophobia scale in children aged 9-13 years. DESIGN: Cross-sectional descriptive observational study. SITE: The pilot study was carried out in December 2019 with students from a school in Ávila and another in Madrid. The field study was carried out during the months of January to March 2020, collecting data from 592 students from a school in Badajoz and 3 from Ávila. PARTICIPANTS: Students of both sexes from 4th, 5th and 6th of Primary Education and from 1st and 2nd of Compulsory Secondary Education, from public and private schools. METHOD: The study has been divided in 2 phases. PHASE I: consisted of the preparation of a 40-item questionnaire with the advice of a panel of experts. This questionnaire was passed, within the pilot study, to 312 children enrolled in Primary Education or Compulsory Secondary Education. After analyzing the results, the 40-item scale was modified to improve the understanding of the schoolchildren and a field study was carried out with 592 participants. PHASE II: consisted of an exploratory factorial analysis carried out using the principal components method, which provided the distribution of the items in 7 components. After the confirmatory factorial analysis, the final 32-item scale was defined. RESULTS: This scale was shown to produce valid and reliable scores. CONCLUSIONS: The validation of this scale will be useful to identify children at risk of nomophobia, allowing educators, parents and health professionals to detect this phenomenon early in order to prevent pathological smartphone use.

HCC risk stratification after cure of hepatitis C in patients with compensated advanced chronic liver disease.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) caused by chronic hepatitis C who have achieved sustained virologic response (SVR). We developed risk stratification algorithms for de novo HCC development after SVR and validated them in an independent cohort. METHODS: We evaluated the occurrence of de novo HCC in a derivation cohort of 527 patients with pre-treatment ACLD and SVR to interferon-free therapy, in whom alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. We validated our results in 1,500 patients with compensated ACLD (cACLD) from other European centers. RESULTS: During a median follow-up (FU) of 41 months, 22/475 patients with cACLD (4.6%, 1.45/100 patient-years) vs. 12/52 decompensated patients (23.1%, 7.00/100 patient-years, p <0.001) developed de novo HCC. Since decompensated patients were at substantial HCC risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de novo HCC development during FU than pre-treatment values or absolute/relative changes. Models based on post-treatment AFP, alcohol consumption (optional), age, LSM, and albumin, accurately predicted de novo HCC development (bootstrapped Harrel's C with/without considering alcohol: 0.893/0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low- (~2/3 of patients) and high-risk (~1/3 of patients) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk: 0% vs. 16.5%) and validation (3.3% vs. 17.5%) cohorts. An alternative approach based on alcohol consumption (optional), age, LSM, and albumin (i.e., without AFP) also showed a robust performance. CONCLUSIONS: Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol consumption, accurately stratified patients with cACLD based on their risk of de novo HCC after SVR. Approximately two-thirds were identified as having an HCC risk <1%/year in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC surveillance. LAY SUMMARY: Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately two-thirds) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound.

International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients.

We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs.

Dual electro-optic comb spectroscopy using a single pseudo-randomly driven modulator.

We present a dual-comb scheme based on a single intensity modulator driven by inexpensive board-level pseudo-random bit sequence generators. The result is a simplified architecture that exhibits a long mutual coherence time (up to 50 s) with no need of stabilization feedback loops or self-correction algorithms. Unlike approaches that employ ultrafast arbitrary waveform generators, our scheme makes it possible to produce long interferograms in the time domain, reducing the difference in the line spacing of the combs even below the hertz level. In order to check the system accuracy, we report two spectroscopic measurements with a frequency sampling of 140 MHz. All these results are analyzed and discussed to evaluate the potential of our scheme to implement a field-deployable dual-comb generator.

Cancellation of reference update-induced 1/f noise in a chirped-pulse DAS.

Distributed acoustic sensors (DAS) perform distributed and dynamic strain or temperature change measurements by comparing a measured time-domain trace with a previous fiber reference state. Large strain or temperature fluctuations or laser frequency noise impose the need to update such a reference, making it necessary to integrate the short-term variation measurements if absolute strain or temperature variations are to be obtained. This has the drawback of introducing a 1/f noise component, as noise is integrated with each cumulative variation measurement, which is detrimental to the determination of very slow processes (i.e., in the mHz frequency range or below). This work analyzes the long-term stability of chirped-pulse phase-sensitive optical time-domain reflectometry (CP-ΦOTDR) with multi-frequency database demodulation (MFDD) to carry out "calibrated" measurements in a DAS along an unmodified SMF. It is shown that, under the conditions studied in this work, a "calibrated" chirped-pulse DAS (CP-DAS) with a completely suppressed reference update-induced 1/f noise component is achieved capable of making measurements over periods of more than 2 months with the same set of references, even when switching off the interrogator during the measurement.

Endoscopic view of the intrahepatic biliary ducts by direct per-oral cholangioscopy in a patient with a choledochal cyst.

Sixty year old female with hypertension and crampy abdominal pain episodes. Admitted to hospital (September-2020) by obstructive jaundice. MRCP: biliary dilation due to Todani Ic (fusiform) choledocal cyst (CC), distal sludge. ERCP: normal mucosa prominent papilla; biliary dilation compatible with CC; choledocholithiasis; 8-mm CHD filling defect. Sphincterotomy, removal of stones/sludge, brush-cytology of the filling defect (pathology: atypias). US: dilation resolution (CBD: 6.5 mm).