Salivary and peri-implant crevicular fluid biomarkers promising predictors of peri-implant disease conditions: Study

Lithuania: A recent systematic review published in The International Journal of Oral & Maxillofacial Implants assessed the recent evidence (2017–2022) to identify salivary and peri-implant crevicular fluid biomarkers with potential prognostic and diagnostic capabilities for peri-implant disease conditions. 

The study found that of all 49 biomarkers evaluated, IL-1β and RANKL were promising as biomarkers of peri-implant disease conditions; however, the researchers suggest the need for clinical studies with a robust methodology to strengthen the evidence base.

“RANKL and IL-1β have the highest diagnostic significance in assessing peri-implant inflammatory conditions, as differences were observed between all three groups (HI < PIM < PI), the researchers wrote.

The study was conducted by Vykintas Pliavga, Lithuanian University of Health Sciences, Kaunas, Lithuania, and colleagues to summarize the latest scientific literature regarding the concentrations of biomarkers in saliva and peri-implant crevicular fluid (PICF) of healthy implant (HI) patients and patients with peri-implant mucositis (PIM) and peri-implantitis (PI).

For this purpose, the researchers performed a literature review according to PRISMA guidelines. The following online databases were used: ScienceDirect, PubMed MEDLINE, and Cochrane Library. A combination of keywords was used, and selection criteria were applied. Selected articles were published between 2017 and 2022, written in English, and conducted in humans. The articles investigated the levels of saliva and PICF biomarkers in peri-implantitis patients and compared them to healthy implant/peri-implant mucositis patients.

The researchers selected 16 publications comprising 1,117 patients with 1,346 implants.

Following were the key findings:

  • Qualitative analysis revealed 49 different biomarkers, the levels of which were compared between groups.
  • After evaluating the most frequently studied biomarkers, significantly higher values of IL-1β, RANKL, sRANKL, IL-6, TNF-α, TNFSF12, MMP2, and MMP8 levels were observed in the PI group than in the HI group.
  • Of the above-listed biomarkers, IL-1β and RANKL demonstrated the highest diagnostic significance as their levels differed among the three groups, with the highest levels in the peri-implantitis group, followed by the peri-implant mucositis group and the lowest levels in the healthy group.

“Of the 49 biomarkers evaluated, RANKL and IL-1β have potentially the highest diagnostic significance in assessing peri-implant inflammatory conditions, as differences were observed between all three groups (HI < PIM < PI), but data from current publications were not adequate to provide strong evidence,” the researchers concluded.

Reference:

Pliavga V, Peceliunaite G, Daugela P, Leketas M, Gervickas A, Juodzbalys G. Peri-implantitis Diagnosis and Prognosis Using Biomarkers: A Systematic Literature Review. Int J Oral Maxillofac Implants. 2023 Dec 12;38(6):1095-1105. doi: 10.11607/jomi.10353. PMID: 38085740.

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Growth hormone mediators linked with unique phenotype of pediatric type 2 diabetes: TODAY analysis

USA: A post hoc secondary analysis of a randomized clinical trial (TODAY) of 398 participants with youth-onset type 2 diabetes (T2D) revealed that growth hormone mediators may be linked with the unique phenotype of pediatric T2D.

The study, published in JAMA Network Open, suggests that changes in plasma growth hormone mediators are linked with loss of glycemic control in youth-onset T2D, with plasma insulin-like growth factor-1 associated with lower risk and growth hormone receptor and insulin-like growth factor binding protein 1 associated with increased risk.

“Changes from baseline to 3 years in plasma concentrations of growth hormone mediators, including growth hormone receptor, insulin-like growth factor-1, and insulin-like growth factor binding protein 1, were associated with measures of insulin resistance and beta cell function and glycemic failure,” the researchers reported.

Youth-onset type 2 diabetes has a more aggressive phenotype than adult-onset T2D, including increased complication risk and rapid loss of glycemic control. Chang Lu, Harvard Medical School, Boston, Massachusetts, and colleagues aimed to identify associations of growth hormone mediators with beta cell function, glycemic failure, and insulin sensitivity in youth-onset type 2 diabetes. The loss of glycemic control was defined as a haemoglobin A1c (HbA1c) level of 8% or more for six months or an inability to wean from insulin therapy.

The post hoc secondary analysis of the TODAY randomized clinical trial included 398 participants (mean age, 13.9 years; 62% girls) from 15 university-affiliated medical centres with available plasma samples from baseline and 36 months.

Participants comprised youth aged 10 to 17 years with a T2D duration of less than 2 years who were randomized to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Participants were followed up for a median of 3.9 years during the trial, ending in 2011.

Exposures included growth hormone receptor (GHR), plasma insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein 1 (IGFBP-1).

The study’s outcomes were (1) loss of glycemic control during the TODAY study and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), high-molecular-weight adiponectin, insulin sensitivity (1/fasting C-peptide), and beta cell function (C-peptide oral disposition index, C-peptide index).

The analysis led to the following findings:

  • A higher increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995) and higher C-peptide index per 100-ng/mL increase in IGF-1 (β, 0.015).
  • A higher increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75) and lower C-peptide index (β, −0.02).
  • A higher increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37) and higher high-molecular-weight adiponectin (β, 431).

In conclusion, the researchers found novel associations of plasma GH mediator levels with measures of glycemia, glycemic failure, beta cell function, and insulin sensitivity in youths with T2D. However, additional mechanistic or longitudinal studies would help to explain the mechanism by which GH mediators impact glycemia or vice versa.

“Whether alterations in GH mediators may facilitate progression from prediabetes to type 2 diabetes or accelerated onset of diabetes complications in youth-onset T2D are important topics for future studies,” the researchers wrote.

Reference:

Lu C, Wolfs D, El ghormli L, et al. Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(2):e240447. doi:10.1001/jamanetworkopen.2024.0447

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New eye drops found safe and effective in diabetic retinopathy and diabetic macular edema in New trial

New eye drop treatment has been found to be safe and tolerable with 100% participants completing the study for diabetic retinopathy and diabetic macular edema, according to data recently released for the phase 1b/2a trial.

These data demonstrate the safety and tolerability of EXN407, as well as clear indications of biological activity, positioning it well for further development as the first topical treatment for retinal vascular diseases such as diabetic retinopathy and diabetic macular oedema. Exonate is now planning to progress EXN407 to the CLEAR-DM (Clinical Evaluation of a New Eyedrop for Alleviating Retinopathy in Diabetic Macular Oedema) Phase IIb clinical trial.

EXN407 is a twice-daily formulation, comprised of a small molecule SRPK1 inhibitor. The eye drop formula exploits SRPK1 involvement in the alternative splicing of vascular endothelial growth factor (VEGF), a protein heavily involved in the regulation of blood vessel growth. Through inhibition of SRPK1, EXN407 can selectively target pro-angiogenic isoforms of VEGF that lead to vascular retinal disease progression via aberrant growth of leaky blood vessels within the eye.

The mild NPDR/DME (NCT04565756) clinical study assessed the safety, tolerability and signals of biological response to EXN407 monotherapy in a double-masked, placebo-controlled Phase Ib/IIa dose-ranging clinical trial in treatment-naïve patients with mild/moderate non-proliferative diabetic retinopathy (NPDR) and mild diabetic macular oedema. The independent Dose Escalation Committee characterised EXN407 as safe and well-tolerated, with 100% of patients completing the study without requiring anti-VEGF rescue, and no major or serious adverse events reported relating to EXN407. Moreover, EXN407 exhibited high levels of tolerability, with drop comfort scores similar to placebo and artificial tears.

In addition to the primary safety and tolerability endpoints, the study concluded that there were promising signals of biological response from EXN407, demonstrating sustained decreases in macular thickness, relative to the placebo group and comparable to previously reported anti-VEGF injections. The trial further noted that EXN407 treatment led to a significant decrease in vascular leakage (60% of EXN407-treated patients relative to 20% placebo) and that EXN407 inhibited further increases to vascular leakage (10% of EXN407-treated patients relative to 50% placebo).

“The Phase Ib/IIa data demonstrate the clear potential of EXN407 as a non-invasive treatment for these devastating, sight-threatening conditions, and the favourable safety profile and biological activity of EXN407 support its continued clinical development in retinal vascular diseases,” said Catherine Beech, chief executive officer of Exonate: “The results suggest that topical ocular EXN407 may provide clinical benefit and substantially reduce the injection burden for patients with diabetic eye disease. We look forward to engaging with strategic partners to support the CLEAR-DM phase IIb trial, which has been designed to fully demonstrate the clinical benefits of EXN407 in NPDR/DME.”

Full results of the Phase Ib/IIa will be presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in May 2024.

About the EXN407 Phase Ib/IIa mild NPDR/DME Trial (NCT04565756)

The double-masked, placebo-controlled dose-ranging Phase Ib/IIa trial randomised 13 treatment-naïve mild diabetic molecular oedema (DMO/DME) patients (defined as Best Corrected Visual Acuity (BCVA) > 69 ETDRS letters and Central Macular Thickness (CMT) between 280 and 420 microns) to one of three twice-daily doses of EXN407 monotherapy, or placebo: 0.5 mg/mL (3 active/2 placebo), 1 mg/mL or 1.5 mg/ml (3 active/1 placebo for each cohort), for eight days. Following the conclusion of the dose escalation phase, 35 treatment-naïve mild DME patients were randomised to EXN407 monotherapy 1.5 mg/ml (23 active/12 placebo) for 85 days. Participants were all followed for one month (to day 113) after discontinuation of EXN407. Rescue medication (standard of care, ranibizumab or aflibercept) was made available.

The primary endpoint was safety/tolerability, and the secondary endpoint was systemic exposure. Exploratory endpoints were effects of EXN407 monotherapy on CMT and vascular leakage. The independent Dose Escalation Committee characterised EXN407 as safe and well-tolerated, with no major or serious drug-related safety concerns. EXN407 also exhibited improved tolerability, with drop comfort scores similar to placebo and artificial tears. Key safety results are summarised below:

• There were a total of four Treatment Emergent Adverse Events (TEAEs) that were considered as probably related (two related to EXN407 and two related to the placebo). There was one additional event considered as definitely related to EXN407. All of these events were ocular TEAEs, were considered mild in severity, did not lead to study discontinuation, and were resolved without treatment.

• None of the patients discontinued eye drop therapy during the course of the trial.

• Reported non-ocular events were consistent with those observed in diabetic populations.

• Exposure of EXN407 into the vascular compartment was low, achieving maximal concentrations by 30 minutes post administration, and blood concentration values returned to BLOQ by approximately four hours, indicating minimal risk of adverse drug reactions in non-ocular tissues. Further, the data indicated that there is little or no risk of accumulation of EXN407.

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Guselkumab Shows Superior Efficacy Over Ustekinumab for treatment of Psoriatic Arthritis: Study

Psoriatic arthritis is a chronic inflammatory condition that affects joints and skin, often causing pain, swelling, and skin lesions. Biologic therapies like guselkumab and ustekinumab have shown promise in managing PsA, but direct comparisons of their efficacy remain scarce.

A recent study published in Rheumatology and Therapy provides compelling evidence regarding the efficacy of guselkumab compared to ustekinumab in the treatment of psoriatic arthritis (PsA). Using individual patient-level data (IPD) analysis, researchers aimed to elucidate the comparative effectiveness of these two biologic treatments, shedding light on their joint and skin efficacy over a 52-week period.

Researchers Thilakarathne P and colleagues conducted an IPD analysis, pooling data from the DISCOVER-1, DISCOVER-2, PSUMMIT-1, and PSUMMIT-2 trials, encompassing a total of 44,115 participants. The analysis focused on evaluating joint and skin efficacy outcomes, including American College of Rheumatology 20% improvement (ACR20) and Psoriasis Area Severity Index 90% reduction (PASI 90) response rates.

Key Findings:

  • Four MetS score trajectory patterns were identified: low-stable, moderate-low, moderate-high, and elevated-increasing.

  • Compared to participants with a low-stable trajectory pattern, those with an elevated-increasing pattern had a higher risk of overall and site-specific cancers.

  • Trajectories of MetS scores were associated with the occurrence of cancers, emphasizing the importance of long-term monitoring and evaluation of MetS.

The study highlights the significance of considering MetS score trajectory patterns in assessing cancer risk, particularly in individuals with elevated or increasing trajectories. Long-term monitoring of MetS may aid in early detection and intervention strategies for cancer prevention.

Reference:

Thilakarathne P, Schubert A, Peterson S, Noel W, Patel BP, Hassan F. Comparing Efficacy of Guselkumab versus Ustekinumab in Patients with Psoriatic Arthritis: An Adjusted Comparison Using Individual Patient Data from the DISCOVER and PSUMMIT Trials. Rheumatol Ther. 2024;11(2):457-474. doi:10.1007/s40744-024-00644-7

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Women with depression face higher CV risk compared to men: Study

People with depression face an increased risk of cardiovascular disease (CVD); however, more women experience CVD following a depression diagnosis than men, according to a new study published today in JACC: Asia. The study investigates the connection between depression and CVD, shedding light on potential mechanisms that contribute to its sex-based differences and underscoring the importance of tailoring CVD prevention and management strategies according to sex-specific factors.

Depression is the third leading cause of morbidity worldwide. Prior research shows that it is associated with a heightened risk of cardiovascular events, including myocardial infarction (MI), angina, stroke and CV mortality. Women with depression are at greater relative risk of developing heart-related negative health outcomes than men, but there is still controversy over the evidence on sex differences in the impact of depression on heart health and the mechanisms underlying this are not well understood.

“The identification of sex-specific factors in the adverse effects of depression on cardiovascular outcomes may help in the development of targeted prevention and treatment strategies that address the specific CVD risks faced by depressed patients,” said Hidehiro Kaneko, MD, assistant professor at the University of Tokyo in Japan and a corresponding author of the study. “A better understanding will allow healthcare providers to optimize care for both men and women with depression, leading to improved CVD outcomes for these populations.”

Researchers in this study evaluated the association between depression and subsequent CVD events by conducting an observational cohort study using the JMDC Claims Database between 2005 and 2022. They identified 4,125,720 participants who met the study’s criteria. The median age was 44 (36-52) years, and 2,370,986 participants were men. Depression was defined as those clinically diagnosed before their initial health checkup.

Using standardized protocols, the study collected participant’s body mass index (BMI), blood pressure and fasting laboratory values at their initial health checkup. The primary outcome was a composite endpoint including MI, angina pectoris, stroke, heart failure (HF) and atrial fibrillation (AF).

Researchers analyzed the statistical significance of differences in clinical characteristics between participants with and without depression. Results indicate that the hazard ratio of depression for CVD was 1.39 in men and 1.64 in women compared with participants without depression. Models also indicate that hazard ratios of depression for MI, angina pectoris, stroke, HF, and AF were higher for women than for men.

Study authors highlight an important discussion regarding the potential mechanisms that may contribute to why depression impacts women’s heart health more than men’s. One explanation is that women may experience more severe and persistent symptoms of depression compared to men, and they may be more likely to have depression during critical periods of hormonal changes, such as pregnancy or menopause.

Other mechanisms include women’s greater susceptibility to traditional risk factors when depressed, such as hypertension, diabetes and obesity, which may contribute to the development of CVD. Differences in healthcare utilization and treatment between men and women and sex-specific differences in biological factors, such as genetics and hormonal profiles, may also increase women’s CVD risk.

“Our study found that the impact of sex differences on the association between depression and cardiovascular outcomes was consistent,” Kaneko said. “Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management. Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

Limitations of the study include the inability to establish direct causality between depression and cardiovascular events and the inability to accurately reflect the severity or duration of depressive symptoms. Potential confounding factors that may influence the association between depression and CVD were not accounted for, such as socioeconomic status. Researchers also acknowledge that COVID-19 may have been a confounder. 

Reference:

Keitaro Senoo, Hidehiro Kaneko, Kensuke Ueno, Yuta Suzuki, Akira Okada, Katsuhito Fujiu, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Kentaro Kamiya, Junya Ako, Koichi Node, Hideo Yasunaga, Issei Komuro, Sex Differences in the Association Between Depression and Incident Cardiovascular Disease, JACC: Asia, 2024, https://doi.org/10.1016/j.jacasi.2023.11.015.

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How does a diabetes drug lessen symptoms of depression?

Research in animals has shown that the diabetes drug dulaglutide, which is a glucagon-like peptide-1 (GLP-1) receptor agonist may reduce symptoms of depression. A new study published in Brain and Behavior reveals the mechanisms that are likely involved.

By conducting a range of tests in mice treated with and without dulaglutide, investigators confirmed the effects of dulaglutide on depressive-like behaviors, and they identified 64 different metabolites and four major pathways in the brain associated with these effects.

Markers of depression and the antidepressant effects of dulaglutide were linked to lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism.

“These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression,” the authors wrote.

Reference:

Man Jin, Shipan Zhang, Boya Huang, Litao Li, Hao Liang, Aihua Ni, Lina Han, Peng Liang, Jing Liu, Haishui Shi, Peiyuan Lv, Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress, Brain and Behavior, https://doi.org/10.1002/brb3.3448.

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Musical Intervention may bring comfort among Patients undergoing Medical Imaging: Study

Patients undergoing imaging procedures often experience psychological distress and discomfort. In response to this challenge, researchers have explored the effectiveness of musical intervention (MI) in alleviating patient anxiety and improving overall comfort during medical imaging.

A recent systematic review (SR) and meta-analysis (MA) sought to evaluate the impact of MI on psychophysiological outcomes in this context. The SR included thirteen articles, which were assessed for quality using the Joanna Briggs Institute (JBI) Checklist. This study was published in the journal Radiography by L. Vieira and colleagues.

Across the studies, MI was commonly delivered through digital playlists, with headphones being the preferred medium. The average volume ranged from 50 to 60 dB, and the musical frequency typically fell between 60 and 80 beats per minute. While no specific music repertoire emerged as the most effective, some articles cited Johann Pachelbel’s “Canon in D major” as a preferred musical theme.

  • Results from the meta-analysis revealed that patients exposed to MI exhibited lower levels of anxiety and heart rate compared to control groups.

  • Furthermore, anxiety levels continued to decrease following MI, contributing to an overall improvement in patient comfort and examination experience.

  • Notably, the experimental group demonstrated a significant reduction in heart rate, particularly in the final phase of the examination, suggesting sustained benefits from MI intervention.

In conclusion, MI presents itself as a promising strategy for enhancing patient comfort and reducing anxiety during medical imaging procedures. Despite the absence of a universally effective music repertoire, the flexibility of MI allows for customization based on patient preferences.

Implementing MI protocols in imaging departments can contribute to a more positive patient experience and potentially improve examination outcomes. This cost-effective and side-effect-free intervention offers healthcare providers a valuable tool for addressing the psychological and emotional challenges faced by patients undergoing medical imaging.

Reference:

Vieira, L., Carvalho, C., Grilo, A., Reis, J., Pires, A. F., Pereira, E., Carolino, E., & Almeida-Silva, M. Effects of a music-based intervention on psychophysiological outcomes of patients undergoing medical imaging procedures: A systematic review and meta-analysis. Radiography (London, England: 1995),2024;30(2):589–604. https://doi.org/10.1016/j.radi.2024.01.014

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Maternal obesity may promote liver cancer among offsprings, reveals study

Obesity, which could reach 50% of the population in certain developed countries by 2030, is a major public health concern. It not only affects the health of those who suffer from it, but could also have serious consequences for their offspring.

Scientists at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the impact of maternal obesity on the risk of developing liver disease and liver cancer. Using an animal model, the team discovered that this risk was indeed much higher in the offspring of mothers suffering from obesity. One of the main causes was the transmission of a disturbed intestinal microbiota from the mother, resulting in a chronic liver disease whose effects became apparent in adulthood. These results, which have yet to be confirmed in humans, are a warning signal and a call for action to limit the deleterious effect of obesity on children. This research is published in the journal JHEP Reports.

The scientific community suspects that maternal obesity disrupts the metabolic balance of the unborn child, and even increases the risk of childhood cancer and colorectal cancer. But to what extent? ‘‘We wanted to understand whether the children of mothers suffering from obesity were at greater risk of developing liver diseases, and by what biological mechanisms,’’ explains Christian Toso, full professor at the UNIGE Faculty of Medicine and director of the Division of digestive surgery at the HUG, who led this research. ‘‘Indeed, while the risk of liver cancer due to a hepatic virus is decreasing, obesity-related liver diseases are constantly on the rise.’’

The scientists studied two groups of female mice: the first fed with a diet rich in fat and sugar – similar to junk food – which rapidly became obese. The second – the control group – was fed normally. All their offspring were fed with a normal diet and were not overweight. The only difference was therefore the maternal obesity of the first group. ‘‘At 20 weeks, which corresponds to adulthood in humans, we could not detect any notable differences,’’ explains Beat Moeckli, junior staff surgeon and researcher in professor Toso’s team, the first author of this work. ‘‘However, at 40 weeks, a senior age in mice, the liver health of the first group began to deteriorate. All the parameters of liver disease – fat deposits, fibrosis, and inflammation – were significantly higher in the offspring of mothers suffering from obesity. And these are the main risk factors for liver cancer in humans’’.

From disease to cancer: the role of microbiota

To confirm whether these mice had a higher risk of developing liver cancer, the team injected two groups of these mice with an oncogenic product just after weaning. And indeed, the offspring of obese mothers had an 80% risk of developing cancer, compared with 20% for the control group. ‘‘The mother’s obesity thus has an impact long after the birth of its offspring, which seem to inherit a dysfunctional microbiota despite their own living conditions,’’ analyses Beat Moeckli. ‘‘Obesity alters the composition and diversity of the mother’s microbiota, which is passed on to the next generation and persists throughout life’’.

However, by placing mice from both groups in the same cage, the scientists observed a normalisation of the microbiota. As mice are coprophagous (they eat their faeces), they quickly share the same microbiotic strains. Bacterial diversity then increased, favouring the good bacteria. As a result, the healthy microbiota naturally regains the upper hand, and the marker of liver disease dramatically decreased. ‘‘We see a clear effect of the microbiota on the risk of developing liver cancer, indicating its central role in transmitting the risk of disease from mother to child.’’

The junk food diet encourages the proliferation of bad bacteria and reduces bacterial diversity. This altered microbiota, transmitted at birth, then leads to greater inflammation in the liver and, over time, generates fibrosis and steatosis (an excessive presence of fat), which in turn increase the risk of developing liver cancer. Normalising the microbiota also normalises the risk of cancer.

And in humans?

These data come from a study on an animal model, in a highly controlled environment. To be applied in a clinical context, they need to be confirmed in humans under real-life conditions. The first stage will consist of an epidemiological study based on large bodies of data obtained from following mothers and their children over several decades. ‘‘However, we already know that it is possible to modify the microbiota, for instance by using probiotics. ‘‘Having highlighted the importance of the microbiome represents a first step towards new therapies,’’ the scientists conclude.

Reference:

Beat Moeckli, Vaihere Delaune, Benoît Gilbert, Quentin Gex, Stephanie Lacotte, Christian Toso, Maternal obesity increases the risk of hepatocellular carcinoma through the transmission of an altered gut microbiome, JHEP Reports, https://doi.org/10.1016/j.jhepr.2024.101056.

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Progesterone tops pessary at protecting women with short cervixes from preterm birth: BMJ

Women with a short cervix around 20 weeks of pregnancy have an increased risk of preterm birth. Preventing preterm birth in pregnant women with a short cervix is a crucial step in protecting the health of the child. Research from Amsterdam UMC now shows that, in pregnant women with a short cervix around 20 weeks, Progesterone (a hormone) is better than a cervical pessary at reducing the risk of severe preterm birth. This study was published today in The BMJ.

“This is an important improvement that can contribute to the reduction of preterm births and the associated complications, such as an increased risk of infant mortality and long-term health problems for the child,” says Eva Pajkrt, professor of obstetrics at Amsterdam UMC.

Preterm birth, defined as birth prior to 37 weeks, remains a serious problem with far-reaching consequences. Approximately 13.5 million children worldwide are born preterm each year. Children who are born preterm are at higher risk for, both physical and developmental, lifelong complications. Preventing preterm birth is therefore a major priority at the obstetrics department of Amsterdam UMC.

Reducing extreme preterm birth

The research team at Amsterdam UMC investigated the best treatment for women with a cervical length shorter than 25 mm at the 20-week ultrasound scan. In 25 centres across the Netherlands participated in this study. Women with a short cervix were eligible for randomization between progesterone and pessary. The results of this study show that Progesterone is more effective than a pessary in reducing extreme preterm birth. This study underlines the importance of measuring the length of the cervix during the 20-week ultrasound scan and informing women with a cervix shorter than 25 mm about the possibility of treatment with Progesterone.

No significant difference

For women with a cervical length between 25 mm and 35 mm, there was no significant difference in the number of complications due to preterm birth between the group taking Progesterone and the group using a pessary. “Based on our study, we recommend measuring the length of the cervix of all pregnant women during the 20-week ultrasound. Women with a cervix shorter than 25 mm should be informed about the possibility of treatment with Progesterone,” says Pajkrt.

The results of this study are of great importance for the healthcare system and can contribute to the reduction of preterm births and the associated complications. With major consequences for both the individual and for our society,” Pajkrt concludes.

Reference:

van Dijk C E, van Gils A L, van Zijl M D, Koullali B, van der Weide M C, van den Akker E S et al. Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks’ gestation: open label, multicentre, randomised, controlled trial BMJ 2024; 384 :e077033 doi:10.1136/bmj-2023-077033.

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Statin Initiation Linked to Reduced Alzheimer’s Risk, Particularly in genetically susceptible elderly: Study

The association between statin use and Alzheimer’s disease (AD) risk, especially in relation to the APOE ε4 allele, has been unclear. A recent longitudinal cohort study aimed to investigate whether statin initiation affects incident AD and cognitive decline differently depending on APOE ε4 status. This study was published in the Neurology journal by Kumar Rajan and colleagues.

Alzheimer’s disease is a progressive neurodegenerative disorder, and identifying interventions to reduce its risk is crucial. Statins, commonly used to manage cholesterol levels, have been proposed as potential candidates due to their anti-inflammatory and neuroprotective properties. However, the impact of statin use on AD risk remains debated.

The study, conducted in urban communities in Chicago, involved 4,807 participants with a mean age of 72 years, including 63% female and 61% non-Hispanic Black individuals. Statin initiation and incident AD diagnoses were recorded during the study period, along with cognitive assessments. The association between statin use and AD risk was analyzed, considering APOE ε4 allele status.

The key findings of the study were:

  • 31% of participants reported statin initiation during the study period.

  • Statin initiation was associated with a reduced risk of incident clinical AD, especially among those with the APOE ε4 allele.

  • Among APOE ε4 carriers, statin initiation was linked to a significantly lower risk of incident AD compared to non-users.

  • APOE ε4 carriers also experienced slower declines in global cognition and episodic memory after statin initiation.

  • However, the association between statin use and cognitive decline was not significant in individuals without the APOE ε4 allele.

The study suggests that statin use may be associated with a reduced risk of incident AD, particularly in individuals carrying the APOE ε4 allele. These findings highlight the potential benefits of statin therapy in reducing AD risk, especially among those genetically predisposed to the disease. Further research, including randomized clinical trials, is warranted to confirm these results and explore the mechanisms underlying this association.

Statin initiation may be linked to a lower risk of Alzheimer’s disease, especially among individuals with the APOE ε4 allele. These findings provide valuable insights into potential preventive strategies for AD and emphasize the importance of personalized approaches to treatment.

Reference:

Rajan, K. B., Mcaninch, E. A., Wilson, R. S., Dhana, A., Evans-Lacko, S., & Evans, D. A. Statin initiation and risk of incident Alzheimer disease and cognitive decline in genetically susceptible older adults. Neurology,2024;102(7). https://doi.org/10.1212/wnl.0000000000209168

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