Study identifies genetic cause for yellow nail syndrome

An analysis of genetic sequencing data and gene and protein expression studies from patients with yellow nail syndrome (YNS) found that defects in the planar cell polarity (PCP) pathway play a significant role in the pathogenesis of YNS. According to the authors, this is the first demonstration of a mechanism explaining YNS development, especially in its congenital form. This study is published in Annals of Internal Medicine.

YNS is a rare disease characterized by the triad of yellow dystrophic nails, lymphedema, and chronic lung disease. The cause of YNS remains largely unknown, although some evidence points to lymphatic vessel development defects as a manifestation of the disease. The genetic cause of YNS, whether congenital or late-onset, remains unknown.

Researchers from the Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center and colleagues studied genetic data from six patients with congenital YNS (cYNS) and five with sporadic YNS (sYNS) to determine the genetic mechanisms underlying the disease. Among the patients with cYNS, their first symptoms appeared prenatally or shortly after birth.

The median age for onset of symptoms for those with sYNS was 12 years. Yellow nails and lung disease were the presenting symptoms in most patients with YNS. The researchers examined next generation sequencing data for all patients with YNS to identify and analyze genetic variants. CELSR1 was highlighted as the principal candidate disease-causing gene with autosomal recessive inheritance. The researchers found that all but one patient with cYNS had biallelic variants in CELSR1.

The remaining patient had a heterozygous loss-of-function variant in FZD6. Both CELSR1 and FZD6 are core molecules in the Wnt/PCP pathway. None of the patients with sYNS had candidate variants in either CELSR1 or FZD6.

The researchers then extracted RNA from all patients to assess the Wnt/PCP pathway expression, and found that the pathway is disrupted both in cYNS patients with genetic variants and, to a lesser degree, in sYNS patients without genetic defects. These results suggest a strong case for the involvement of Wnt/PCP signaling and PCP defects in the pathogenesis of YNS.

Reference:

Alina Kurolap, Chofit Chai Gadot, Impaired Wnt/Planar Cell Polarity Signaling in Yellow Nail Syndrome, Annals of Internal Medicine,  https://doi.org/10.7326/ANNALS-24-01101

Powered by WPeMatico

Vagus nerve stimulation relieves severe depression, reports research

People with severe, treatment-resistant depression who received a nerve-stimulating therapy showed significant improvement in depressive symptoms, quality of life and ability to complete everyday tasks after a year, according to the results of a national, multicenter clinical trial led by Washington University School of Medicine in St. Louis. The findings are published Dec. 18 in a pair of papers in the journal Brain Stimulation.

The study involved nearly 500 participants at 84 sites across the U.S. All of the participants suffered from severe depression that could not be treated effectively with medication or other approaches. This study represents one arm of the RECOVER trial; the other arm addresses bipolar depression and is ongoing. Three quarters of the participants were so ill they were unable to work. Each participant was implanted with a device that stimulates the left vagus nerve-a major conduit between the brain and the internal organs-but only half the devices were turned on. The researchers tracked the participants’ responses using multiple validated assessment tools. While the primary assessment tool revealed no significant differences between the on and off groups, many of the other measures showed significant benefits to using the device.

“These patients are extremely ill, and most have been for a very long time,” said Charles R. Conway, MD, a professor of psychiatry at WashU Medicine and the principal investigator of the RECOVER trial. “On average, each patient had already tried 13 treatments that failed to help them before they enrolled in the trial, and they had spent more than half of their lives sick with depression. But despite that super-high level of sustained illness, we still see statistically significant, measurable improvements in depressive symptoms, quality of life and functional outcomes.”

The improvements observed are potentially life-changing for these patients with severe, refractory depression, Conway said. Severe depression can render people “paralyzed by life,” unable to accomplish the tasks of daily living. The amount of improvement experienced by the participants could be the difference between being unable to get out of bed and being productive and effectively interacting with loved ones, Conway said.

A vagus nerve stimulation device was approved by the Food and Drug Administration (FDA) nearly two decades ago for treatment-resistant depression, but it has not become widely available. Between the cost of the device itself and the surgery to implant it, the therapy can be unaffordable for many patients, as the Centers for Medicare and Medicaid Services (CMS) and most private insurance plans currently don’t cover it.

Designed with an eye toward gathering the data that CMS needs to determine whether to cover the therapy, the RECOVER study aims to evaluate the effectiveness of vagus nerve stimulation therapy for treatment-resistant depression, both alone and as part of bipolar disorder. Many private health insurance companies follow the lead of CMS when it comes to coverage, so a decision by CMS to cover the device and the implantation surgery could make the therapy available to many more people. CMS helped design the RECOVER study and provided some funding.

Vagus nerve stimulation therapy for treatment-resistant depression involves implanting a pacemaker-like device under the skin in the chest with a wire connected to the left vagus nerve in the neck. The device is part of the VNS Therapy System manufactured by LivaNova USA, Inc., which also sponsored and funded the trial in partnership with CMS.

The VNS Therapy device emits stimulation to the nerve, which in turn sends electrical pulses to areas of the brain associated with mood regulation. In this study, 493 people were implanted with devices and approximately half (249) of the devices were activated for the 12-month randomized control period. The other half of the devices did not have active stimulation during the control period.

The first two months of the 12-month trial period were dedicated to getting the devices’ electrical parameters properly adjusted to each patient. Starting in month three, the researchers obtained monthly evaluations of the participants’ depressive symptoms using four validated assessment tools, two of which were completed by blinded, off-site clinicians on the research team, one by an on-site psychiatrist or psychologist, and one by the patients themselves. The participants also rated their own quality of life and ability to perform the tasks of daily living every three months using three validated tools for quality of life and two for functional abilities.

All participants were already in treatment for depression and continued seeing their treating mental-health providers during the trial. Providers were discouraged from starting patients on new antidepressant treatments during the trial, but those who were already receiving treatments were encouraged to continue with them. Outcomes were measured in terms of the percentage of time participants experienced relief of depressive symptoms.

Overall, people with activated devices spent significantly more time with improved symptoms than did those with inactive devices. Complete remission was rare and did not differ between groups. People with activated devices also reported significant improvement in quality of life and functional abilities.

“What’s really important here is that patients themselves were reporting that their lives were improving,” Conway said. “You have a population of people that has been failed by a ridiculously high number of treatments, including very aggressive treatments such as electroconvulsive therapy. And they’re not just saying, ‘Yeah, I feel a little better.’ They’re saying they are seeing meaningful improvements in their ability to function and live their lives. And the nice thing about vagus nerve stimulation, we know from other studies, is that when the patient responds, the effects usually stick.”

Most of the improvements weren’t seen until the last three months of the trial. This finding was unsurprising, given that potential improvements from vagus nerve stimulation are known to progress slowly over the first year of treatment. At the end of the year, the devices that had been off during the 12-month control period were turned on. The primary outcome measure failed to show a significant difference between the two treatment groups, because the off group reported more improvement than expected, particularly in the last several weeks. Of note, all participants knew that the devices would be activated at year’s end, which may have affected those in the control group who knew potential relief was forthcoming, said Conway.

The participants will be followed for another four years to determine how long the effects last and how much the participants ultimately benefit. In addition, researchers are working on identifying patients’ characteristics tied to the greatest response.

Reference:

Conway, Charles R. et al., Vagus Nerve Stimulation in Treatment-Resistant Depression: A One-Year, Randomized, Sham-Controlled Trial, Brain Stimulation, DOI:10.1016/j.brs.2024.12.1191.

Powered by WPeMatico

Development of global innovative drug in eye drop form for treating dry age-related macular degeneration

Age related macular degeneration (AMD) is the leading cause of vision loss in individuals over 65, characterized by abnormal changes in the macular, resulting in reduced vision and distorted objects. Dry AMD accounts for 90% of all AMD cases, with relatively mild vision impairment; however, approximately 30% progress to the severe vision loss associated with wet AMD within 10 years. The only FDA-approved treatments for dry AMD as of 2023 are two injectable drugs, which are limited by concerns over complications from intravitreal injections and modest efficacy in restoring vision.

The research team led by Dr. Moon-Hyeong Seo from the Natural Product Drug Development Center at the Korea Institute of Science and Technology (KIST, President Oh Sang-Rok) has developed a new therapeutic agent for dry AMD that can be administered as eye drops. Eye drops are the most preferred drug delivery method in the ophthalmic market, yet developing eye drop formulations targeting the retina, located in the posterior segment of the eye, remains a significant challenge.

To address the limitations of injection-based treatments, the research team focused on the inflammatory signaling pathway of Toll-like receptors (TLRs), which are known to play a critical role in AMD pathogenesis. By extracting peptide sequences from tens of thousands of proteins with structures similar to natural TLR signaling proteins, they established an extensive library of over 190,000 peptide drug candidates. Utilizing advanced technology for rapidly screening peptides that specifically bind to TLR signaling proteins, they successfully identified multiple candidate peptides capable of inhibiting interactions between these proteins.

The researchers validated the therapeutic efficacy of the peptides by administering them as eye drops to mice with induced dry AMD. The treated group exhibited retinal cell protection and significantly reduced retinal degeneration, comparable to normal mice. This demonstrated that peptide-based eye drops could effectively replace existing injectable therapies for dry AMD.

This new therapeutic agent, delivered in eye drop form, offers enhanced treatment convenience and adherence for patients while reducing complications and costs associated with repetitive invasive treatments. Furthermore, the non-invasive and safe nature of the therapy provides a novel treatment option that improves both efficacy and patient satisfaction. This innovation is expected to revolutionize the treatment accessibility of AMD and other related ophthalmic conditions.

Dr. Seo stated, “The KIST Natural Product Drug Development Center, established in September to focus on mission-driven research, aims to develop global drugs targeting aging-related diseases, including cancer and ophthalmic conditions. We plan to pursue collaborative research with domestic and international pharmaceutical companies to advance global clinical trials for this innovative dry AMD therapeutic.”

Reference:

Yun Lim, Tae Kyeom Kang, Meong Il Kim, Dohyeon Kim, Ji Yul Kim, Sang Hoon Jung, Keunwan Park, Wook-Bin Lee, Moon-Hyeong Seo, Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides, Advanced Science, https://doi.org/10.1002/advs.202406018

Powered by WPeMatico

New Clinical Trial Supports QX004N’s Safety and Effectiveness for Patients With Plaque Psoriasis

China: A new randomized clinical trial has demonstrated that QX004N, a humanized anti–IL–23 monoclonal antibody, offers superior safety and efficacy compared to a placebo in patients with moderate to severe plaque psoriasis. The findings, published in JAMA Dermatology, emphasize the potential of QX004N as a promising treatment option for individuals struggling with this chronic skin condition.

Results revealed that QX004N was well-tolerated and exhibited greater therapeutic benefit, achieving a higher rate of skin clearance than the placebo.

Psoriasis is a chronic, immune-driven skin condition with a significant need for effective biologic treatment options. IL-23 is a cytokine involved in inflammation and immune system regulation, and targeting it has been a key focus in developing new psoriasis treatments. QX004N, by inhibiting IL-23, addresses the immune dysfunction central to plaque psoriasis, aiming to reduce inflammation and control disease progression.

Against the above background, Xiaojiao Li, Phase I Clinical Trial Center, the First Hospital of Jilin University, Changchun, China, and colleagues aimed to evaluate the safety, pharmacokinetics, and efficacy of QX004N in both healthy individuals and patients with moderate to severe plaque psoriasis in China.

For this purpose, the researchers conducted a two-part randomized clinical trial in China to evaluate the safety, pharmacokinetics, and efficacy of QX004N. Part 1 was a first-in-human, single-ascending-dose phase 1a trial from November 2, 2021, to January 16, 2023, involving healthy participants receiving QX004N (10–600 mg) or placebo in a 4:1 ratio. Part 2 was a double-blind, multiple dose-escalation phase 1b trial from February 15, 2023, to January 5, 2024, involving patients with moderate to severe plaque psoriasis assigned similarly to receive 150 mg, 300 mg, or 600 mg of QX004N or placebo every two weeks.

The primary outcome of part 1 focused on safety and pharmacokinetics, while the primary endpoint of part 2 was achieving a 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12.

The following were the key findings of the study:

  • The Phase 1a clinical trial enrolled 55 healthy participants with a mean age of 35.9 years (54.5% female).
  • The phase 1b clinical trial included 30 patients with moderate to severe plaque psoriasis.
  • In part 2, the mean age of QX004N-treated participants was 41.4 years (79.2% male), while the mean age of the placebo group was 35.3 years (83.3% male).
  • QX004N demonstrated linear pharmacokinetics and was well tolerated by healthy participants and psoriasis patients.
  • Most adverse events were mild to moderate, with no drug-related serious adverse events reported.
  • At week 12, 100% of patients receiving QX004N in the 150-mg, 300-mg, and 600-mg doses achieved PASI 75 (75% improvement in PASI), significantly higher than the 33.3% observed in the placebo group.
  • At week 16, 100% of QX004N-treated participants achieved PASI 90 (90% improvement in PASI).
  • The maximum proportion of participants achieving an Investigator’s Global Assessment score of 0 or 1 was 100% across all three QX004N dose groups.

The authors concluded that this phase 1a and 1b randomized clinical trial demonstrated that QX004N is safe and well-tolerated in healthy individuals and patients with moderate to severe plaque psoriasis in China. Treatment with QX004N at doses of 150 mg to 600 mg biweekly resulted in 100% of patients achieving a PASI 75 response by week 12, sustained through week 24, which was significantly higher than the placebo group.

“These findings support the continued development of QX004N as a promising treatment option for improving outcomes in patients with moderate to severe plaque psoriasis,” they wrote.

Reference:

Li X, Li B, Yang D, et al. Safety and Efficacy of Anti–IL-23 Monoclonal Antibody QX004N for Patients With Psoriasis: A Randomized Clinical Trial. JAMA Dermatol. Published online December 11, 2024. doi:10.1001/jamadermatol.2024.5059

Powered by WPeMatico

Prophylactic Trimetazidine may prevent contrast induced AKI in patients undergoing CAG or PCI: Study

Prophylactic Trimetazidine may prevent contrast induced AKI in patients undergoing CAG or PCI suggests a study published in the BMC Nephrology.

Contrast-induced acute kidney injury (CI-AKI) is a known complication after coronary angiography (CAG) or percutaneous coronary intervention (PCI). Clinical evidence suggests that trimetazidine (TMZ), an anti-ischemic drug, may prevent CI-AKI. We aimed to evaluate the role of trimetazidine in preventing CI-AKI in patients with pre-existing renal dysfunction undergoing CAG or PCI. They searched PubMed, Cochrane Library, EBSCOhost, Web of Science, and Google Scholar databases from January 2004 to January 2024. We reviewed RCTs involving participants aged ≥ 18 years with pre-existing renal insufficiency who underwent CAG or PCI. Outcomes should include the incidence of CI-AKI, adverse events, and changes in serum creatinine (Scr) levels at different time intervals. Two reviewers independently extracted the data, evaluated the quality and relevance of the studies, and graded the strength of evidence for each study through consensus. Results: Nine RCTs met the inclusion criteria and assessed the role of TMZ in patients with renal dysfunction who underwent CAG or PCI. All RCTs showed a significant decrease in the incidence of CI-AKI in the TMZ group compared to the control group (RR 0.36, 95% CI, [0.25, 0.52] P < 0.001). Changes in Scr at 24 h (SMD -0.33, 95% CI, [-0.56, -0.10], P = 0.01), at 48 h (SMD -0.27, 95% CI, [-0.46, -0.09], P = 0.01), and 72 h (SMD -0.32, 95% CI, [-0.56, -0.07], P = 0.01) were statistically significant in the TMZ group compared to the control group. However, the changes in Scr beyond 72 h following CAG or PCI were statistically insignificant in the TMZ group when compared to the control group (SMD -0.22, 95% CI, [-0.52, 0.09], P = 0.16). The incidence of adverse effects was lower in the TMZ group than in the control group, and the difference was statistically significant (RR 0.51, 95% CI, [0.29, 0.90]; P = 0.02).

The addition of TMZ to standard hydration protocols may offer a promising strategy for lowering the incidence of CI-AKI, adverse events, and postoperative SCr levels in patients with renal insufficiency within 72 h after CAG or PCI. However, large-scale RCTs are necessary to definitively establish the efficacy and safety of TMZ in patients with renal insufficiency after CAG or PCI.

Reference:

Lukwaro, A., Lu, Y., Chen, J. et al. Trimetazidine as an adjunct to standard hydration reduces the incidence of contrast-induced acute kidney injury in patients with renal insufficiency undergoing coronary angiography or percutaneous cardiac intervention: a systematic review and meta-analysis.. BMC Nephrol 25, 471 (2024). https://doi.org/10.1186/s12882-024-03872-9

Keywords:

Prophylactic, Trimetazidine, prevent, contrast, induced, AKI, patients, undergoing, CAG, PCI, Study, BMC Nephrology, Lukwaro, A., Lu, Y., Chen, J

Powered by WPeMatico

LNG-IUD safe and effective for managing heavy menstrual bleeding in adolescents with inherited bleeding disorders: Study

One in four adolescents with heavy menstrual bleeding (HMB)
since menarche may have an inherited bleeding disorder (IBD).
Levonorgestrel-containing intrauterine devices (LNG-IUDs) are the preferred
treatment for HMB in adolescents owing to the substantial and extended
reduction in bleeding and favorable side effect profile. Medical management
alone is frequently insufficient in persons with IBDs, yet several barriers
impact the use of LNG-IUDs in those with IBDs, including a lack of standardized
periprocedural guidelines, perceived higher bleeding risk associated with IUD
insertion complications, and placement-related pain. In addition, a recent
history of HMB increases the risk of IUD expulsion threefold. Moreover, first
spontaneous IUD expulsion is more frequent among adolescents, potentially because
of small uterine size. Expulsion risk factors include young age, history of
anemia, concurrent bleeding disorder diagnosis, and abnormal uterine bleeding.
While the LNG-IUD is as effective for HMB treatment in adolescents with IBDs as
those without IBDs, a key barrier to securing this extended efficacy is a more
frequent IUD expulsion rate within 30 days of insertion. Importantly,
expulsions after 30 days are not more frequent than in adolescents without
IBDs.

Cygan et al hypothesize dthat prophylactic menstrual
suppression after IUD insertion may reduce early (≤30 days) device expulsion.
The primary objective was to examine the rates of early IUD expulsion in
adolescents with IBDs with concurrent menstrual suppression.

The Penn State Health Women and Girls Bleeding Disorder
Clinic provides women’s health services for patients with suspected or
confirmed IBDs, including Ehlers-Danlos syndrome. This retrospective study included
adolescent girls (aged 10–21 years) with known or suspected IBDs undergoing IUD
insertion between November 1st, 2019 and September 7th, 2022. According to the
clinic practice pattern, participants continued their prior hormonal therapy
for at least 30 days after insertion. IUD insertion was within 60 days of the
last depot medroxyprogesterone acetate injection to ensure adequate coverage
for 30 days. Assessed data included the incidence of IUD expulsion, bleeding
disorder diagnosis, mode of menstrual suppression in the first 30 days after
insertion, subjective reported bleeding profiles at follow-up, and any observed
complications. Bleeding patterns were categorized as amenorrheic, light,
normal, or heavy.

Chart review identified 24 IUD insertions in 22 adolescents.
First follow-up for all 24 insertions occurred approximately 30 days after
insertion (mean 30 days).

For patients initially seen at 30 days, a second follow-up
visit was reviewed to confirm at least 30-day compliance with menstrual
suppression, evaluate bleeding pattern, and assess IUD status.

Hormonal menstrual suppression was utilized for 22 of 24
(92%) insertions.

Menstrual suppression was shown to be effective, with 14 of
24 patients (58%) reporting light bleeding and seven of 24 patients (29%)
reporting amenorrhea.

Altogether, no early expulsions because of excess bleeding
were noted after any of the 24 IUD insertions. There were no expulsions because
of heavy bleeding before 30 days for 21 of 22 individuals. One individual with
type IIA von Willebrand disease had two expulsions (the first within 30 days of
insertion and the second within 4 months [137 days]), neither associated with
excessive bleeding.

Given the absence of HMB, expulsions in this youngest
individual in the cohort were likely attributable to uterine size. A subsequent
19.5-mg LNGIUD inserted 1 year later remained in place for >12 months. One
individual experienced partial expulsion in the setting of excess bleeding more
than 6 months after placement, supporting the relationship between heavy blood
flow and displacement of the IUD from the endometrial cavity. One IUD was
electively removed within 4 months because of cramping without excessive
bleeding. No other expulsions were observed at the final follow-up. This
includes five individuals evaluated through 6 months and 11 individuals
followed through 12 months.

At final follow-up, for those whose IUDs remained in place,
bleeding was well controlled; 11 of 19 (58%) had amenorrhea and seven of 19
(36%) had light bleeding. In addition, there was no uterine perforation,
hemorrhage, or bleeding that required further hemostatic interventions.

No early (≤30 days after insertion) IUD expulsions because
of heavy bleeding were observed. If the risk for IUD expulsion in IBDs is
decreased during the first menses following insertion, the LNG-IUD’s favorable
bleeding profile may contribute to lower rates of late expulsion once patients
experience a reduction in monthly blood loss. While acknowledging that this
study is limited by loss of follow-up and subjective assessment of bleeding
profile improvement, the absence of early expulsion observed here in the
context of menstrual suppression is a promising improvement over similarly
sized studies that have reported higher rates of IUD expulsion in adolescents
with IBDs. The LNG-IUD is a safe and effective method of managing HMB in
adolescents with IBDs. Concurrent menstrual suppression for at least 30 days
after insertion, to prevent bleeding-related early expulsion in this
population, may maximize safety and minimize complications for this at-risk
group.

Source: CYGAN et al.; Int J Gynecol Obstet. 2024;00:1–4.

DOI: 10.1002/ijgo.16063

Powered by WPeMatico

Women with Endometriosis and uterine fibroids likely to have Premature death, suggests study

A new study published in the British Medical Journal showed that women who have a history of uterine fibroids and endometriosis may be more likely to die young after they have finished having children. With clinically significant prevalences of 10% and 15% to 30%, respectively, endometriosis and uterine fibroids are prevalent conditions among women in their reproductive years.

Growth of endometrial-like tissue outside the uterus is a hallmark of endometriosis. Uterine fibroids, on the other hand, are smooth muscle cell-based, non-cancerous tumors that usually develop inside or near the myometrium. But uterine fibroids and endometriosis have similar genetic roots, and they grow through a combination of proinflammatory, immunological, and endocrine mechanisms. As a result, Yi-Xin Wang looked at how endometriosis and uterine fibroids affected the long-term risk of premature death in women from the Nurses’ Health Study II (NHSII), which has been conducted every two years for 30 years in the United States.

In 1989, 110,091 women between the ages of 25 and 42 who had never had a hysterectomy previously were diagnosed with cancer, cardiovascular disease, or endometriosis or fibroids were included. The key performance indicators Hazard ratios (calculated using Cox proportional hazards models) for overall and cause-specific premature death based on uterine fibroids confirmed by ultrasound or hysterectomy or endometriosis verified by laparoscopy and reported in biennial questionnaires.

Over the course of 2994,354 person years of follow-up, 4356 premature deaths were documented, including 90 from respiratory illnesses, 304 from cardiovascular disorders, and 1459 from cancer. Women with and without laparoscopically diagnosed endometriosis had crude incidences of all-cause premature death of 2.01 and 1.40 per 1000 person years, respectively.

Laparoscopically verified endometriosis was linked to a hazard ratio of 1.19 for premature mortality in age-adjusted models and these models were reinforced after controlling for behavioral variables and other possible confounders. In cause-specific mortality studies, uterine fibroids verified by ultrasound or hysterectomy were linked to a higher chance of dying from a malignant tumor of gynecological organs, but not to all cause premature death.

Women who reported both endometriosis and uterine fibroids had a higher risk of premature mortality from all causes. Overall, women who had a history of endometriosis and uterine fibroids were more likely to die young and die from gynecological malignancies.

Source:

Wang, Y.-X., Farland, L. V., Gaskins, A. J., Wang, S., Terry, K. L., Rexrode, K. M., Rich-Edwards, J. W., Tamimi, R., Chavarro, J. E., & Missmer, S. A. (2024). Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. In BMJ (p. e078797). BMJ. https://doi.org/10.1136/bmj-2023-078797

Powered by WPeMatico

Sarcopenic obesity may increase risk of knee osteoarthritis, finds research

A new study published in the PLOS ONE journal showed that in middle-aged and older Chinese people, obesity, sarcopenic obesity, and low muscular strength were linked to an increased risk of occurrence of symptomatic knee osteoarthritis (OA) seven years later.

The growing number of people at risk for osteoarthritis and other health issues is a result of the changing aging demographics and the rising incidence of obesity. About 80% of all cases of OA worldwide are caused by knee OA, which is a common ailment. Sarcopenia is a physiological phenomenon that naturally happens with aging and is characterized by a loss of muscle mass and strength that can be increased by co-morbid illness states.

Also, obesity raises the risk of sarcopenia due to ectopically accumulated lipids and chronic inflammation in skeletal muscle. This study examined whether reduced muscular strength may mediate the effects of obesity on the start of knee OA in middle-aged and older Chinese populations, as well as the possible impacts of muscle strength and sarcopenic obesity on the incidence of knee OA.

The China Health and Retirement Longitudinal Study yielded a total of 12,043 participants. Using Poisson regression models, the effects of sarcopenic obesity on the development of knee OA were computed. The mediating proportion of muscular strength on the relationship between obesity and incidence of knee OA was estimated using mediation analysis.

A total of 12,043 people were included in the trial, and 2,008 of them developed knee OA. Poisson analysis showed a causal relationship between the start of knee OA and both abdominal and overall obesity. The participants who had the greatest degree of normalized grip strength were 0.33 times less likely to experience incident knee OA than those in the control group, and chair-rising time was linked to a 0.65-fold higher risk of incident knee OA.

Similar findings were found via sensitivity analysis. When compared to the reference group, the participants with sarcopenic obesity had an approximately twofold increased incidence of acute knee OA. The relationship between obesity and the incidence of knee OA was mediated by normalized grip strength and chair-rising time. Overall, the study found that incidence-symptomatic knee OA is influenced by sarcopenic obesity and low muscular strength in middle-aged and older Chinese individuals. 

Source:

Yan, L., Ge, H., Wang, Z., Shen, A., Xu, Q., Jiang, D., & Cao, Y. (2024). Roles of low muscle strength and sarcopenic obesity on incident symptomatic knee osteoarthritis: A longitudinal cohort study. In S. Agostini (Ed.), PLOS ONE (Vol. 19, Issue 10, p. e0311423). Public Library of Science (PLoS). https://doi.org/10.1371/journal.pone.0311423

Powered by WPeMatico

Increased maternal butylparaben exposure elevates risk of asthma: Study

A recent study published in the Environmental Pollution journal highlighted how prenatal exposure to certain chemicals, commonly found in everyday products, may contribute to asthma development in children. This study analyzed the effects of maternal urinary phenol concentrations during early pregnancy on childhood asthma risk at age four.

The research examined a total of 3,513 mother-child pairs enrolled in the Japan Environment and Children’s Study (JECS) Sub-Cohort Study. Maternal urine samples, collected during the first trimester of pregnancy, were tested for 24 types of phenols, including parabens, bisphenol A, octylphenol, and nonylphenol. Also, phenol levels varied widely among participants. One key finding was that methylparaben was present at high concentrations in almost all samples, with an average level of 267.7 ng/ml and a large variation across individuals.

The analysis revealed significant associations between prenatal exposure to certain phenols and the risk of asthma in children. High levels of butylparaben in maternal urine were linked to a 54% increase in the odds of asthma onset by age four. Meanwhile, exposure to 4-nonylphenol showed a gender-specific effect where the boys born to mothers with detectable levels of this compound had more than double the odds of developing asthma (odds ratio: 2.09), and the girls showed no significant increase in risk.

These findings underline the complexity of phenol exposure and its potential to impact children’s health differently based on gender and chemical type. While the mechanisms remain unclear, the results indicate that certain phenols act as endocrine disruptors, possibly influencing respiratory health through hormonal pathways.

The study provides a crucial step toward understanding the risks of prenatal chemical exposure. Given that many of these phenols are widely used in consumer products, the findings emphasize the need for increased awareness and potential regulation to minimize exposure during pregnancy. And so, avoiding products containing butylparaben or nonylphenol during pregnancy might help reduce the risk of asthma in children.

Overall, these findings will inspire further studies to investigate the biological pathways involved and inform future public health guidelines to protect vulnerable populations, particularly pregnant women and children.

Reference:

Kuraoka, S., Oda, M., Ohba, T., Mitsubuchi, H., Nakamura, K., Katoh, T., Kamijima, M., Yamazaki, S., Ohya, Y., Kishi, R., Yaegashi, N., Hashimoto, K., Mori, C., Ito, S., Yamagata, Z., Inadera, H., Nakayama, T., Sobue, T., Shima, M., … Katoh, T. (2024). Association of phenol exposure during pregnancy and asthma development in children: The Japan Environment and Children’s study. In Environmental Pollution (Vol. 361, p. 124801). Elsevier BV. https://doi.org/10.1016/j.envpol.2024.124801

Powered by WPeMatico

Risk of bleeding after dental extractions rather low among patients on antiplatelet therapy, suggests study

A study published in BMC Oral Health suggests that the risk of bleeding after dental extractions is rather low among patients on antiplatelet therapy.

This retrospective study aimed to identify high-risk dental extraction patients and the timing of postoperative haemorrhage to evaluate whether preventive hospitalization should be considered in patients on antiplatelet medication (AP) or anticoagulants. The study included 1595 procedures; 1319 were conducted under monotherapy (Group I: AP; Group II: indirect oral anticoagulant [IAC]; Group III: direct oral anticoagulant [DOAC]) and 276 under dual therapy (Group IV: double AP; Group V: AP and IAC; Group VI: AP and DOAC). We evaluated the incidence, frequency and timing of haemorrhage, hospitalization rate, and treatment of bleeding incidents. Results: The incidence of hemorrhagic events was significantly higher in the dual therapy groups compared to the monotherapy groups (p < 0.001). Comparing the procedures under monotherapy, those on DOAC (Group III) had a significantly higher risk of postoperative bleeding than Groups I and II (p < 0.001) and a higher rate of repeated bleeding episodes (p = 0.035).

Regarding bleeding incidents, 44% (dual therapy) vs. 51.1% (monotherapy) occurred on the day of surgery. The bleeding risk after dental extractions is overall low and patients were often hospitalized preventively due to their comorbidities rather than actual bleeding risk. Patients should be instructed about local compression, and surgeries should be completed in the morning to avoid emergency visits. However, patients with cardiovascular diseases and dual therapy had a higher risk of postoperative haemorrhage. Thus, hospitalization is to be considered in these cases.

Reference:

Katz, M.S., Benidamou, R., Ooms, M. et al. Influence of antiplatelet medication and anticoagulation therapy after dental extractions on hospitalization: a retrospective 10-year study. BMC Oral Health 24, 1485 (2024). https://doi.org/10.1186/s12903-024-05275-6

Keywords:

A study published in BMC Oral Health suggests that the risk of bleeding after dental extractions is rather low among patients on antiplatelet therapy.

The aim of this retrospective study was to identify high-risk dental extraction patients and the timing of postoperative hemorrhage to evaluate whether preventive hospitalization should be considered in patients on antiplatelet medication (AP) or anticoagulants. The study included 1595 procedures; 1319 were conducted under monotherapy (Group I: AP; Group II: indirect oral anticoagulant [IAC]; Group III: direct oral anticoagulant [DOAC]) and 276 under dual therapy (Group IV: double AP; Group V: AP and IAC; Group VI: AP and DOAC). We evaluated the incidence, frequency and timing of hemorrhage, hospitalization rate, and treatment of bleeding incidents. Results: The incidence of hemorrhagic events was significantly higher in the dual therapy groups compared to the monotherapy groups (p < 0.001). Comparing the procedures under monotherapy, those on DOAC (Group III) had a significantly higher risk of postoperative bleeding than Groups I and II (p < 0.001) and a higher rate of repeated bleeding episodes (p = 0.035). Regarding bleeding incidents, 44% (dual therapy) vs. 51.1% (monotherapy) occurred on the day of surgery. The bleeding risk after dental extractions is overall low and patients were often hospitalized preventively due to their comorbidities rather than actual bleeding risk. Patients should be instructed about local compression, and surgeries should be completed in the morning to avoid emergency visits. However, patients with cardiovascular diseases and dual therapy had a higher risk of postoperative hemorrhage. Thus, hospitalization is to be considered in these cases.


Reference:

Katz, M.S., Benidamou, R., Ooms, M. et al. Influence of antiplatelet medication and anticoagulation therapy after dental extractions on hospitalization: a retrospective 10-year study. BMC Oral Health 24, 1485 (2024). https://doi.org/10.1186/s12903-024-05275-6


Keywords:

Risk, bleeding, after, dental, extractions, rather, low, among, patients, antiplatelet, therapy ,study, BMC Oral Health, Katz, M.S., Benidamou, R., Ooms, M, Postoperative bleeding, Antiplatelet therapy, Oral anticoagulation, Dental extraction, Hospitalization, Risk patients

Powered by WPeMatico