New Potential treatment found for patients suffering from Myasthenia Gravis: Study

For the thousands of people globally affected by the disease myasthenia gravis (MG), everyday activities become a struggle, and in severe cases, the disease can be life-threatening.

Until now, there has been no muscle-specific and effective treatment against this rare autoimmune disease that leads to severe weakening of the muscles and fatigue. But now, a team of researchers from Aarhus University reveals a breakthrough in the treatment of MG that could give hope to many patients worldwide.

“The patients simply became stronger because the new treatment improves the communication between motor nerves and muscle fibers,” says Thomas Holm Pedersen, an associate professor at the Department of Biomedicine at Aarhus University, CEO of NMD Pharma, and the lead author of the study that has just been published in the journal Science Translational Medicine.

Focusing on the link between nerve cells and muscles

MG is a disease where the immune system attacks the connection between nerves and muscle cells. It can affect breathing and be life-threatening, and it was precisely these symptoms that the researchers aimed to combat by strengthening the function of the contact point between nerves and muscle cells.

During his PhD project at Aarhus University, Thomas Holm Pedersen discovered that the so-called CIC-1 chloride channels at the neuromuscular junction are crucial for muscle activation.

“This led to the idea of using the CI channels as a new treatment point for diseases where the neuromuscular connection is compromised, including myasthenia gravis,” he explains.

And it proved to be a good idea. The researchers demonstrated that they could effectively strengthen the muscles’ ability to respond to nerve impulses by targeting a treatment at the specific channel. This, in theory, could increase muscle strength and reduce fatigue in patients.

“As there were no medications targeting the Cl channel, we first had to find the right molecule that we could test in patients, which requires considerable work and various tests before the regulatory authorities allow testing in humans. We tested it on patients who had to take a tablet daily for their muscle weakness and fatigue, and we could see that the treatment concept worked. The patients became stronger.

Treatment without side effects?

This represents a significant advance in the treatment of MG. Not only because it was successful in increasing muscle strength among patients, but also because the treatment, unlike existing methods, may well prove to be free from side effects.

“We won’t know for sure for a few years, after we’ve conducted more studies, but it looks really promising right now,” says Thomas Holm Pedersen.

The breakthrough could result in a significant improvement in the quality of life for patients struggling with MG, but it is also a big leap forward in the understanding and treatment of other neuromuscular diseases.

The research team is currently planning more follow-up clinical trials, including another study on MG and one on the hereditary disease spinal muscular atrophy, which leads to muscle wasting.

According to Thomas Holm Pedersen, we may be on the verge of a paradigm shift in the treatment of MG and other serious neuromuscular diseases.

“This study summarizes years of work here at Aarhus University and NMD Pharma. We have proven that the method works in patients, and now we continue with the clinical trials to bring the drug to the patients and to explore its broader application,” he says.

Reference:

Martin Skov et al. ,The ClC-1 chloride channel inhibitor NMD670 improves skeletal muscle function in rat models and patients with myasthenia gravis.Sci. Transl. Med.16,eadk9109(2024).DOI:10.1126/scitranslmed.adk9109.

Powered by WPeMatico

Adults with ideal CV health have lower risk of developing heart disease, stroke or kidney disease later in life: AHA

An analysis of health data for nearly 4 million young adults in Korea found that those who had ideal cardiovascular health had about a 65% lower risk of developing heart disease, stroke or kidney disease later in life compared to people with low heart health scores, according to preliminary research to be presented at the American Heart Association’s Epidemiology and Prevention, Lifestyle and Cardiometabolic Scientific Sessions 2024, March 18- 21, in Chicago. The meeting offers the latest science on population-based health and wellness and implications for lifestyle.

In a 2023 scientific statement and presidential advisory, the American Heart Association highlighted the link between heart disease and chronic kidney disease and the importance of improving cardiovascular health to prevent them.

“Cardiovascular disease is deadly, and kidney disease is quite common, even among younger adults,” said lead study author Hokyou Lee, M.D., Ph.D., an associate professor of preventive medicine at Yonsei University College of Medicine in Seoul, South Korea. “These two diseases should be prevented together because they often coexist or increase the likelihood of one another. However, the importance of ideal heart health behaviors and factors in young adults have often been overlooked due to their lower short-term risk of cardiovascular and kidney diseases.”

In this study, researchers reviewed data from the 2009-2010 Korean National Health Screening program to explore how cardiovascular health during young adulthood affects the risk of developing heart disease, stroke and kidney disease later in life. Participants’ heart health was assessed and scored using the three modifiable lifestyle behaviors and three health measures: being physically active, maintaining a healthy weight and quitting tobacco and blood pressure, cholesterol and blood sugar, from the American Heart Association’s Life’s Simple 7 metrics. (Note: In 2022, sleep health was added to the seven metrics in the Association’s new Life’s Essential 8 measures for optimal cardiovascular health.)

The analysis found:

  • Young adults with perfect heart health scores at enrollment had a 65% lower risk of developing cardiovascular or kidney disease during the 12-year follow-up compared to people with zero ideal cardiovascular health metrics. Note: In this study, a perfect heart health score was 6 out of 6 because a measure of diet was not available for participants.
  • The risk of developing cardiovascular or kidney disease decreased gradually with higher heart health scores.
  • People whose scores improved from low to high during follow-up also had a lower risk of developing cardiovascular or kidney disease compared to people who had consistently low heart health scores.

“Less than 1% of the young adults had ideal heart health scores at the beginning of the study, and, unfortunately, about half of those with perfect or near-perfect cardiovascular health eventually had lower heart health scores within a few years. However, fewer of the young adults with perfect or near-perfect cardiovascular health whose scores decreased experienced cardiovascular and kidney diseases than young adults who began with low heart health and remained that way,” Lee said. “Our study highlights the importance of achieving ideal cardiovascular health during young adulthood and maintaining or improving it throughout life. More effort is needed to raise awareness among young adults about implementing and maintaining heart-healthy lifestyle behaviors early in life to help them live longer, healthier lives.”

Study background information:

  • The study included 3,836,283 adults in South Korea who did not have a history of cardiovascular or kidney disease.
  • Participants self-identified as female (38.2%) and male (62.8%).
  • Participants were ages 20-39 years old, with a median age of 31 at the beginning of the study.

The study’s limitations included that it did not use the new Life’s Essential 8 health metrics to define cardiovascular health. In addition, dietary information about participants was not available, and the study included only people living in South Korea, which limits the generalizability of the study’s findings to other populations.

“The findings underscore the importance of early awareness of risk factors and intervention and the adoption of healthy lifestyle behaviors in young adulthood to prevent cardiovascular and kidney diseases later in life. Moreover, the research indicates that even individuals with initially low heart health scores who improved their cardiovascular health over time experienced a reduced risk of diseases compared to those with persistently low scores. This highlights the potential for positive health outcomes through lifestyle modifications,” said

Monica C. Serra, Ph.D., an associate professor and research investigator in the department of medicine in the Division of Geriatrics, Gerontology & Palliative Medicine and the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT Health San Antonio in San Antonio, Texas. Serra is co-chair of the program committee of EPI│Lifestyle Scientific Sessions 2024.

“The use of the American Heart Association’s Life’s Simple 7 metrics, including modifiable behaviors such as physical activity, weight management and tobacco cessation, along with biometric measures like blood pressure, cholesterol and blood sugar, provides a comprehensive assessment of heart health. It is noteworthy that the study did not include dietary components, and the addition of sleep health in the Association’s new Life’s Essential 8 was acknowledged,” she said. “Overall, the research contributes valuable evidence to the importance of cardiovascular health maintenance in young adulthood for long-term disease prevention.”

Reference:

Adults younger than 40 with ideal heart health had lower heart disease, stroke, and kidney disease risk, American Heart Association, Meeting: AHA EPI|Lifestyle Scientific Sessions 2024.

Powered by WPeMatico

Survival rate of Metal–ceramic and monolithic zirconia implants 100% after 5 years, reveals study

The survival rate of Metal–ceramic and monolithic zirconia implants is 100% after 5 years, reveals a study published in the Journal of Clinical Medicine.

The current study aimed to present the clinical and radiological outcomes of monolithic zirconia superstructures compared to the metal–ceramic ones in the All-on-4 concept for the prosthetic rehabilitation of the maxillae. A total of 30 patients were subdivided into groups according to their superstructure type (metal–ceramic (n = 15) or monolithic zirconia (n = 15)). All implants were functionally loaded within 24 h after insertion with provisional acrylic superstructures. Prosthetic complications, marginal bone loss, plaque accumulation, probing pocket depth, bleeding on probing, and bite force were documented over 5 years. Marginal bone loss around the implants of the ceramic group remained well over the five years (1.21 ± 0.23 mm). However, marginal bone loss was significantly lower around the implants in the monolithic zirconia group (0.22 ± 0.14 mm) (p < 0.001). Bleeding on probing, plaque accumulation, and probing pocket depth values were correlated with marginal bone loss. Among all evaluated parameters, no differences could be detected in terms of the angulation of the implants. Detachment or chipping was observed in seven cases in the metal–ceramic superstructure group. In all cases, dentures were removed and repaired in the laboratory. In the monolithic zirconia group, chipping was detected after one year in two cases, after two years in four cases, and after five years in one case and could be managed by polishing in situ. Monolithic zirconia superstructures presented superior results regarding the parameters evaluated.

Reference:

Ayna M, Jepsen S. A Retrospective Evaluation of 5 Years of Clinical Results of Metal–Ceramic vs. Monolithic Zirconia Superstructures in Maxillary All-on-4TM Concept. Journal of Clinical Medicine. 2024; 13(2):557. https://doi.org/10.3390/jcm13020557

Keywords:

Survival rate, Metal–ceramic, monolithic zirconia implants,Ayna M, Jepsen S, Journal of Clinical Medicine, immediate loading; metal–ceramic; zirconia

Powered by WPeMatico

Cataract surgery and iStent Inject combo tied to significantly greater reduction of IOP in mild glaucoma patients: Study

Cataract surgery and iStent Inject combo tied to significantly greater reduction of IOP in mild glaucoma patients suggests a study published in the Ophthalmology Glaucoma.

A study was done to evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular micro bypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. Eyes with visually-significant cataracts and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 – 30 mmHg on 0 to 3 ocular hypotensive medications. Participants’ eyes were randomised (2017-2020) 1:1 to combine cataract surgery with iStent Inject (treatment group, n=56) or cataract surgery alone (control group, n=48), and followed up for two years. The co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24 months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24 months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. Results: Participants (67.3% male) were aged 53-85 years and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2 to 1.1, p=0.008). 57% of eyes in the treatment group were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the two groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the two groups. The visual outcomes and safety profiles were similar between the two groups. Combined cataract surgery with iStent Inject achieved a clinically- and statistically significantly greater reduction in ocular hypotensive medication usage at 24 months compared to cataract surgery alone, with no significant difference in IOP.

Reference:

Jennifer C. Fan Gaskin, Deus Bigirimana, George Yu Xiang Kong, Myra B. McGuinness, Alp Atik, Lei Liu, Anne MV. Brooks, Ghee Soon Ang. Prospective, Randomised Controlled Trial of Cataract Surgery versus combined Cataract Surgery with insertion of iStent Inject, Ophthalmology Glaucoma, 2024, ISSN 2589-4196, https://doi.org/10.1016/j.ogla.2024.02.004.

(https://www.sciencedirect.com/science/article/pii/S2589419624000310)

Keywords:

Cataract surgery, iStent, Inject, reduction of IOP, mild glaucoma patients, Ophthalmology Glaucoma, Glaucoma; glaucoma surgery; minimally- invasive glaucoma surgery; intraocular pressure, Jennifer C. Fan Gaskin, Deus Bigirimana, George Yu Xiang Kong, Myra B. McGuinness, Alp Atik, Lei Liu, Anne MV. Brooks, Ghee Soon Ang

Powered by WPeMatico

Study busts myth: Smoking doesn’t help to stay thin, increases belly fat

The worry of gaining weight is a common excuse for smokers not to quit. A new study published today in the scientific journal Addiction has found that both starting smoking and lifetime smoking may increase abdominal fat, especially visceral fat: the unhealthy fat deep inside the abdomen that is linked to a higher risk of heart disease, diabetes, stroke, and dementia.

Smokers tend to have lower body weights than non-smokers, but they also have more abdominal fat, and more abdominal visceral fat. Visceral fat is hard to see; you can have a flat stomach and still have unhealthy amounts of it, raising your risk of serious illness. This new study offers supportive evidence that smoking may cause that type of fat to increase.

Researchers at the NNF Center for Basic Metabolic Research, University of Copenhagen used a form of statistical analysis called Mendelian randomization (MR) to determine whether smoking causes an increase in abdominal fat. MR combines the results from different genetic studies to look for causal relationships between an exposure (in this case, smoking) and outcome (increased abdominal fat). This new study combined multiple genetic results from European ancestry studies of smoking exposures and measures of body fat distribution (e.g., waist-hip ratio and waist and hip circumferences).

First, the researchers used previous genetic studies to identify which genes are linked to smoking habits and body fat distribution. Second, they used this genetic information to determine whether people with genes associated with smoking tend to have different body fat distributions. Finally, they accounted for other influences, such as alcohol consumption or socioeconomic background, to ensure that any connections they found between smoking and body fat distribution were truly due to smoking itself and not other factors.

Lead author Dr. Germán D. Carrasquilla explains: “This study found that starting to smoke and smoking over a lifetime might cause an increase in belly fat, as seen by measurements of waist-to-hip ratio. In a further analysis, we also found that the type of fat that increases is more likely the visceral fat, rather than the fat just under the skin.”

“Previous studies have been prone to confounding, which happens when an independent variable affects the results. Because our study design uses genetic variations, it does a better job of reducing or controlling for those variables. The influence of smoking on belly fat seems to happen regardless of other factors such as socioeconomic status, alcohol use, ADHD, or how much of a risk-taker someone is.”

“From a public health point of view, these findings reinforce the importance of large-scale efforts to prevent and reduce smoking in the general population, as this may also help to reduce abdominal visceral fat and all the chronic diseases that are related to it. Reducing one major health risk in the population will, indirectly, reduce another major health risk.”

The researchers determined that excess abdominal fat in smokers was predominantly visceral fat by studying how DNA variants linked to smoking habits and belly fat relate to fat compartments in different parts of the body. The key finding is that these genetic factors are more strongly linked to increased visceral adipose tissue-the deep fat that wraps around the abdominal organs-than to subcutaneous fat that is stored under the skin.

The two underlying European ancestry studies were large in scale: the smoking study looked at 1.2 million people who started smoking and over 450,000 lifetime smokers, and the body fat distribution study included over 600,000 people.  

Reference:

Germán D. Carrasquilla, Mario García-Ureña, María J. Romero-Lado, Tuomas O. Kilpeläinen, Estimating causality between smoking and abdominal obesity by Mendelian randomization, Addiction, https://doi.org/10.1111/add.16454.

Powered by WPeMatico

Morphological characteristics of vestibular aqueduct associated with occurrence of Meniere disease: Study

Morphological characteristics of vestibular aqueduct associated with the occurrence of Meniere disease suggest a study published in the Largnygoscope.

A study was done to investigate the relationship between vestibular aqueduct (VA) morphology and Meniere’s disease (MD) using ultrahigh-resolution computed tomography (U-HRCT). Retrospective data were collected from 34 patients (40 ears) diagnosed with MD in our hospital who underwent temporal bone U-HRCT with the isotropic 0.05-mm resolution, magnetic resonance with gadolinium-enhanced, and pure-tone audiometry; 34 age- and sex-matched controls (68 ears) who underwent U-HRCT were also included. VA patency was qualitatively classified as locally not shown (grade 1), locally faintly shown (grade 2), or clearly shown throughout (grade 3). The width of the outer orifice and VA length and angle were quantitatively measured. Differences in VA morphology between the MD and control groups were analyzed. The correlations between VA morphology and the degrees of hearing loss and endolymphatic hydrops (EH) were also analyzed. Results: VA was classified as grades 1–3 in 11, 17, and 12 ears in the MD group and 5, 26, and 37 ears in the control group, respectively. The patency differed significantly between the groups (p < 0.01). The width of the outer orifice and length of VA were significantly smaller in the MD group than those in the control group (p < 0.05). Both VA patency and length were correlated with the degree of EH in the cochlea and the vestibule (p < 0.05). No difference was found between VA morphology and the degree of hearing loss (p > 0.05). The morphological characteristics of VA were found to be associated with the occurrence of MD and the degree of EH.

Reference:

Huang, Y., Tang, R., Xu, N., Ding, H., Pu, W., Xie, J., Yang, Z., Liu, Y., Gong, S., Wang, Z. and Zhao, P. (2024), Association Between Vestibular Aqueduct Morphology and Meniere’s Disease. The Laryngoscope. https://doi.org/10.1002/lary.31339

Keywords:

Morphological characteristics, vestibular aqueduct, occurrence, Meniere disease, Largnygoscope, Huang, Y., Tang, R., Xu, N., Ding, H., Pu, W., Xie, J., Yang, Z., Liu, Y., Gong, S., Wang, Z. and Zhao, P

Powered by WPeMatico

Lipoprotein (a) assay methods similarly predict MACE reduction with PCSK9 inhibitor Alirocumab: Study

USA: A recent comparison of changes in lipoprotein(a) mass and molar concentrations found that each essay method is similarly predictive of major adverse cardiovascular events (MACE) reductions with alirocumab (ALI).

The study stated, “With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, three Lp(a) assay methods appeared comparably predictive of ALI MACE reduction, independent of reduction in LDL cholesterol,”

The findings were published online in the European Journal of Preventive Cardiology on March 19, 2024.

Baseline (BL) lipoprotein (a) concentrations are similarly related to cardiovascular (CV) risk when measured in either molar units or mass by immunoassay (IA). Because of Lp(a) isoform variation in mass, there may be differences between Lp(a) measurement methods in terms of relating change to risk reduction.

Against the above background, Michael Szarek, Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA, and colleagues determined whether the reduction in MACE by PCSK9 inhibitor alirocumab has a similar relationship to the reduction in Lp (a) concentration as measured by three different methods.

Lipoprotein (a) was measured by IA-molar (Roche), IA-mass (Siemens), and mass spectrometry (MS)-molar assays at baseline and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial. The trial compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome.

Changes in Lp(a) from baseline to M4 were related to subsequent risk of MACE (nonfatal myocardial infarction, coronary heart disease death, unstable angina hospitalization, or fatal + nonfatal ischemic stroke) in the ALI group. Proportional hazard models were adjusted for baseline Lp(a), baseline LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay.

The study led to the following findings:

  • Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE.
  • Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while a change in IA-molar concentration was marginally significant; associations were more evident with coronary heart disease death + nonfatal MI.
  • MACE HRs for median change were similar across tests.

In conclusion, despite the relatively low number of MACE available for analysis, only moderately elevated lipoprotein levels, and intra-patient variability in serial value, the researchers showed that each of the 3 Lp(a) assay methods was similarly predictive of modest MACE reductions with alirocumab treatment.

“Greater clinical benefits might be observed, with the emergence of new potent Lp(a) lowering agents,” the researchers wrote.

Reference:

Szarek, M., Reijnders, E., Steg, P. G., Jukema, J. W., Schwertfeger, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Fazio, S., Garon, G., Goodman, S. G., Harrington, R. A., White, H. D., Zeiher, A. M., Cobbaert, C., & Schwartz, G. G. Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwae110

Powered by WPeMatico

Add on Benzbromarone outperformed febuxostat monotherapy in gout with combined-type hyperuricemia: JAMA

China: The addition of low-dose benzbromarone (25 mg/day) to low-dose (20 mg/day) febuxostat showed superior urate lowering versus febuxostat monotherapy in gout with a combined-type hyperuricemia, a recent study in Arthritis Care & Research has shown.

“For selected patients, expedited achievement of the serum urate (SU) target in more than 75% of patients using one titration step and low xanthine oxidase inhibitor and uricosuric doses is a potential alternative to standard urate-lowering therapy (ULT) regimens,” the researchers reported.

In gout, increased SU, called hyperuricemia, promotes crystal deposition of monosodium urate monohydrate crystals in periarticular and articular structures that can trigger acute episodes of very painful inflammatory arthritis (gout flare). Longstanding hyperuricemia and gout can also lead to joint damage, palpable tophi, and urolithiasis.

Urate-lowering therapy is the central strategy for effectively controlling hyperuricemia and gout, but there has been an unmet need for simpler ULT regimens that achieve the serum urate target and improve the overall quality of gout care. Therefore, Xiaomei Xue, Affiliated Hospital of Qingdao University, Qingdao, China, and colleagues reported a comparative effectiveness trial of febuxostat monotherapy versus benzbromarone add-on to low-dose febuxostat in gout specifically with combined renal urate underexcretion and overload.

The research team conducted a prospective randomized trial on patients with combined-type hyperuricemia and estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2. They were randomly assigned in 1:1 ratio to febuxostat and benzbromarone combination therapy (initially febuxostat at 20 mg/day, with benzbromarone at 25 mg/day added onto 20 mg/day of febuxostat if not at target) or febuxostat monotherapy (initially 20 mg/day, escalating to 40 mg/day if not at target).

The primary endpoint at 12 weeks was the proportion achieving an SU level <360 μmol/L. Other outcomes were altered kidney and liver function, gout flares, and new-onset urolithiasis.

Following were the study’s key findings:

  • Two hundred and fifty participants were randomized; 219 completed 12-week treatment.
  • More patients in the febuxostat and benzbromarone combination group achieved the SU target compared to patients in the febuxostat monotherapy group (75.5% vs 47.7%; odds ratio 3.37).
  • Safety profiles were comparable between the two groups.

The findings showed the superiority of low-dose benzbromarone add-on to low-dose febuxostat compared with febuxostat monotherapy in gout with combined-type hyperuricemia.

“For selected patients, expedited achievement of the SU target in more than 75% of patients using one titration step and low xanthine oxidase inhibitor and uricosuric doses is a potential alternative to standard ULT regimens,” the researchers concluded.

Reference:

Xue, X., Sun, M., Yan, F., Dalbeth, N., He, Y., Li, X., Qi, H., Chen, Y., Yuan, X., Li, M., Ji, A., Terkeltaub, R., & Li, C. Superiority of Low-Dose Benzbromarone Add-On to Low-Dose Febuxostat Compared With Febuxostat Monotherapy in Gout With Combined-Type Hyperuricemia. Arthritis Care & Research. https://doi.org/10.1002/acr.25283

Powered by WPeMatico

VCTE-based scores can accurately predict liver-related events in MASLD patients: JAMA

China: A cohort study of 16 603 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) who underwent vibration–controlled transient elastography (VCTE) examination showed VCTE-based scores to be accurate for predicting liver-related events.

The findings, published in the Journal of the American Medical Association (JAMA), suggest VCTE-based scores are a suitable alternative to liver biopsy in routine clinical practice and phase 2b and 3 clinical trials for steatohepatitis.

“The VCTE-based scores outperformed most noninvasive tests and were at least comparable if not better than histologic fibrosis staging in predicting liver-related events,” the researchers reported. “On repeated testing, the scores were largely stable, and there was a substantial reduction in the risk of liver-related events in patients with improved scores.”

Currently, MASLD is the most common chronic liver disease worldwide. Therefore, developing noninvasive tests to assess the disease severity and prognosis is important. Considering this, Huapeng Lin, The Chinese University of Hong Kong, Hong Kong, China, and colleagues aimed to study the prognostic implications of baseline levels and dynamic changes of the VCTE–based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.

The study included data from a natural history cohort of MASLD patients who underwent VCTE examination at 16 tertiary referral centers in Europe, the US, and Asia from 2004 to 2023, of which the prospective collection of data was done at 14 centers.

The study included adults aged at least 18 years with hepatic steatosis diagnosed by imaging studies (computed tomography, ultrasonography, or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE) or histologic methods (steatosis in ≥5% of hepatocytes).

The primary outcomes were liver-related events (LREs), denied as hepatocellular carcinoma or hepatic decompensation (variceal hemorrhage, ascites, hepatorenal syndrome, or hepatic encephalopathy), liver-related deaths, and liver transplants. The Agile scores were compared with histologic and eight other noninvasive tests.

The researchers reported the following findings:

  • A total of 16 603 patients underwent VCTE examination at baseline (mean age, 52.5 years; 57.8% were male). At a median follow-up of 51.7 months, 1.9% developed LREs.
  • Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89).
  • 65.8% of patients had repeated VCTE examination at a median interval of 15 months and were included in the serial analysis.
  • 81.9% of patients had stable Agile 3+ scores, and 92.6% of patients had stable Agile 4 scores (same risk categories at both assessments).
  • The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores.
  • In patients with a high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with a substantial reduction in the risk of LREs.
  • A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group.

In conclusion, the findings suggest that single or serial Agile scores are highly accurate in predicting liver-related events in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and phase 2b and 3 clinical trials for steatohepatitis.

Reference:

Lin H, Lee HW, Yip TC, et al. Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease. JAMA. Published online March 21, 2024. doi:10.1001/jama.2024.1447

Powered by WPeMatico

Increased Risk of Severe COVID-19 Observed in People with Epilepsy: Study

A recent retrospective study revealed concerning findings regarding the susceptibility of people with epilepsy (PWE) to severe COVID-19. The key findings of the study were published in the journal of Epilepsia.

This study by Huw Strafford and team spanned from March 1, 2020 to June 30, 2021 and the analysis involved linked electronic health records of the SAIL databank from hospital admissions and primary care data for the Welsh population. This research conducted in Wales identified 27,279 individuals with epilepsy during the study period and matched with 136,395 controls based on sex, age and socioeconomic status. The data showed that PWE underwent a significantly increased risk of both hospitalization due to COVID-19 and death from the virus when compared to their matched counterparts.

Among the individuals with PWE, there were a total of 158 COVID-19 deaths and 933 hospitalizations, while in the control group 370 deaths and 1871 hospitalizations were reported. The hazard ratios for COVID-19 death and hospitalization in PWE when compared to controls were high at 2.15, even after adjusting for comorbidities that were known to exacerbate the COVID-19 risks.

The significance of these findings underscore the urgent need for tailored strategies to protect and prioritize PWE against COVID-19. The outcomes of this study emphasized the importance of characterizing this elevated risk to inform both individuals with epilepsy and healthcare planning moving forward.

These revelations prompt considerations for future distribution of vaccine and treatment prioritization efforts. The health authorities may need to reassess vaccination strategies to ensure equitable access and protection for this population with a better understanding of the increased vulnerability of PWE to severe COVID-19 outcomes.

Reference:

Strafford, H., Hollinghurst, J., Lacey, A. S., Akbari, A., Watkins, A., Paterson, J., Jennings, D., Lyons, R. A., Powell, H. R., Kerr, M. P., Chin, R. F., & Pickrell, W. O. (2024). Epilepsy and the risk of COVID‐19‐related hospitalization and death: A population study. In Epilepsia. Wiley. https://doi.org/10.1111/epi.17910

Powered by WPeMatico