Aug 28

Amoxicillin Treatment for Syphilis: Can an Old Drug Learn a New Trick?

The CDC reports that syphilis cases have increased among males and females, in all regions of the United States, and in all age groups, including congenital syphilis. In 2021, there were 176,713 cases, representing a 28.6% increase from 2020.1 Intramuscular benzathine penicillin G (BPG) is widely recommended2-3 as the first-line treatment for primary, secondary, latent and tertiary syphilis without CNS involvement, with reported success rates of 90-100%.4 Although not mentioned by the World Health Organization (WHO) and CDC guidelines, oral amoxicillin is included in the Japanese and United Kingdom guidelines. For early syphilis, amoxicillin 500 mg three times daily is a first-line option in the Japanese guidelines5, whereas amoxicillin 500 mg four times daily plus probenecid 500 mg four times daily is an alternative in the United Kingdom guidelines.6 Ando et al conducted an open-label, randomized controlled trial to assess the non-inferiority of two amoxicillin-based regimens for the syphilis treatment at a single center in Japan. Patients with HIV, age ≥20 years, and diagnosed with syphilis by positive Treponema pallidum hemagglutination (TPHA) and a positive rapid plasma regain (RPR) test were included. Positive RPR titers were defined as the following: an RPR titer greater than 8, an RPR titer equal to 8 with clinical symptoms compatible of primary or secondary syphilis, or at least a 4-fold rise in RPR titer. Pregnant and lactating individuals and patients with neurosyphilis were excluded from the study. Patients were randomized 1:1 to receive amoxicillin 500 mg three times daily (Japanese guideline dosage) or amoxicillin 1000 mg plus probenecid 250 mg three times daily. In both groups, patients with early syphilis received a 14-day course while patients with late syphilis received a 28-day course. Follow up visits were conducted at 3,6,9 and 12 months after treatment. The primary outcome was serological cure rate at 12 months, defined as a four-fold decrease or negative conversion in RPR titer by the conventional test, using per protocol analysis. The non-inferiority margin was 10%. Self-reported medication adherence and adverse effects including nausea, diarrhea, vomiting, drug allergy, Jarisch-Herxheimer reactions were assessed at the second visit. Between August 2018 and February 2022, a total of 112 patients were enrolled. All study participants identified as male, the median age was 39, and 97% of participants were Asian. The majority of patients took antiretroviral therapy (91%) and had HIV viral load <200 copies/mL (84.8%). The median RPR titer at diagnosis was 64 (IQR 32-128) and the majority of patients had early syphilis. Four patients that missed follow up appointments due to COVID-19 stay-at-home orders were excluded from analysis at the applicable timepoints. Amoxicillin monotherapy did not demonstrate non-inferiority to amoxicillin/probenecid for serological cure rate at 12 months (Table). Similar trends were confirmed with automated RPR testing. No significant differences between adverse effects or medication adherence were observed; 105 participants (93.8%) reported taking more than 95% of the regimen. Advertisement This study describes the effectiveness of amoxicillin-based regimens with similar observed effectiveness to first-line syphilis therapies including BPG and doxycycline. 4.8 As a low-cost oral regimen, amoxicillin with probenecid may provide advantages for select patients. Medication adherence to a multiday amoxicillin regimen is crucial, compared to single-dose or weekly intramuscular BPG administered by a healthcare professional. Alternative treatment options are particularly vital when managing medication shortages and as of April 2023 there is an ongoing shortage of BPG in the United States due to increased demand for the medication. The CDC has issued guidance to prioritize BPG supply for patients with no alternative treatment options: pregnant people with syphilis and babies with congenital syphilis.3 Of note, the probenecid dose used in this study varies from recommendations in the UK guideline and package insert. 6,7 Probenecid inhibits tubular secretion of penicillin and subsequently increases penicillin serum concentration.7 While treponemicidal amoxicillin serum concentrations have been described6, this study did not assess medication concentration levels in participants. Further prospective studies of amoxicillin/probenecid regimens for syphilis treatment in people without HIV and women should be conducted to optimize the dosing regimen and demonstrate safety and effectiveness in a diverse patient population. Article Citation: Ando, N., Mizushima, D., Omata, K., et al. Combination of Amoxicillin 3,000 mg and Probenecid versus 1,500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients with HIV: an Open-Label, Randomized, Controlled, Non-Inferiority Trial. Clin Infect Dis. 2023 May 9;ciad278. doi: 10.1093/cid/ciad278. Online ahead of print. References Centers for Disease Control and Prevention. (2023, May 16). National Overview of STDs, 2021. Centers for Disease Control and Prevention. https://www.cdc.gov/std/statistics/2021/overview.htm#Syphilis Workowski, K. A., Bachmann, L. H., Chan, P. A., et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187. doi: 10.15585/mmwr.rr7004a1 Guidelines for the management of symptomatic sexually transmitted infections. (2021). World Health Organization. Clement ME, Okeke NL, and Hicks CB. Treatment of syphilis: a systematic review. JAMA. 2014 Nov 12;312(18):1905-17. doi: 10.1001/jama.2014.13259. Japanese Society for Sexually Transmitted Infections. The Japanese STI diagnosis and treatment guidelines [in Japanese]. 2016. http://jssti.umin.jp/pdf/guideline-2016_v2.pdf Kingston, M., French, P., Higgins, S., et al. UK national guidelines on the management of syphilis 2015. Int J STD AIDS. 2016 May;27(6):421-46. doi:10.1177/0956462415624059. Epub 2015 Dec 31. Probenecid [package insert]. Lannett Company Inc; Philadelphia (PA): July 2012 Dai T, Qu R, Liu J, Zhou P, Wang Q. Efficacy of Doxycycline in the Treatment of Syphilis. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01092-16. doi: 10.1128/AAC.01092-16.

Aug 28

Opinion | Eva’s full but too-short life leaves a lasting legacy of love

Eva was born with CDG, a condition you are unlikely to have heard of. Congenital Disorders of Glycosylation is the collective term for a large group of rare and complex genetic, metabolic diseases which affect all parts of the body, including the brain. Diagnosis is a devastating moment for any parent – it all but guarantees that your child will face continual, grievous challenges, require round-the-clock care, and have a shortened lifespan. Symptoms in infancy include low muscle tone, poor growth, developmental delays, seizures and stroke-like episodes and heart problems. There is much to come to terms with. My dear cousin Jill and her husband Paul went through this anguished process following the birth of Eva. They were forced to rethink their hopes and expectations for her, and to reconstruct their lives around her care. Tough days and great sacrifice lay ahead. They did all this willingly, and with deep love and dedication. Despite her profound disabilities, Eva had a full and fulfilling existence. She rode horses and made trips to the beach in a specially built wheelchair. She attended and enjoyed school. She and her younger sisters, twins Sofia and Iona, were as close as siblings can be. Eva passed away on August 8, at the age of 12. Last week, I travelled to Cambridgeshire, where Jill and her family live, for the funeral. Ahead of time, I was dreading it – the loss of a child, even the thought of it, is unthinkably painful. As I hugged Jill – what to say? – I stupidly asked how she was doing. “Oh, you know…” she replied, before adding gently, “Well, you don’t, and I hope you never do.” I felt my heart break. A funeral entirely at one with nature Eva’s funeral was an occasion I will never forget, though not only for the reasons you can imagine. It took place deep in the Cambridgeshire countryside, at the Barton Woodland Burial Ground, which covers almost 40 acres. More than 20,000 trees have been planted there, including oak, ash, lime, wild cherry and silver birch. Birds chirp and butterflies flit among the flowers as the breeze blows softly through the branches. There are no gravestones or monuments – only biodegradable wooden plaques on the ground. It feels like a subtle, serene, sylvan heaven. Flowers and trees make the Barton Woodland Burial Ground a peaceful place to be (Image: Picasa) Appropriately, the entire funeral was at one with nature. Eva arrived in a small, electric hearse, and lay in a woven casket. The service was held in a wooden, chalet-style building, led by a humanist celebrant, and interspersed with readings from those who had known and loved Eva best. There were lots of tears, but also many smiles amid the reflections – how she had her mother’s sparkling blue eyes and her father’s wide, warming smile, how visitors to the house would be expected to pay court to “Queen Eva” until they were dismissed, how her belly laugh would fill the room – and, oh, how she loved to laugh. Eva had lessons to teach us all Like all children, she could be naughty: she was never happier than when playing with her sisters, though if they got too big for their boots, she would tug their hair to remind them who was boss. She bore the traumas of her condition, the seizures and hospital visits, with fortitude, and lived in and for the moment. Eva had lessons to teach us all – we who constantly fret over trivial, passing matters, so often missing the larger point of things. Her six-year-old sisters sat beside her, in shining yellow sundresses, on this final journey Throughout the afternoon, Jill and Paul showed a dignity and bravery that I found almost unfathomable – and when Jill addressed us all, it was with a mother’s raw heartbreak coupled with immense pride in and love for her daughter. Then Eva was placed on an open, flower-strewn carriage and pulled to her place of rest by a great, white horse. Her six-year-old sisters sat beside her, in shining yellow sundresses, on this final journey, as the rest of us walked behind, the only sounds our footsteps, the trundle of the wheels and the occasional equine neigh. An astonishing outpouring of love Within an hour of the funeral’s end, I was on a train back to Scotland, gazing through the window and struggling to absorb the immensity of the experience. I thought of my excitement whenever I used to make childhood visits to see Jill and her brother Nicky. They were my glamorous, slightly older cousins: Jill sharp and beautiful and funny, Nicky cool and dry, with an enviable array of Marvel comics and an impressive record collection. I always wanted to be more like them. Geographical distance means we don’t see each other as often as I’d like these days, but I still look up to them. I thought of how the young girl that was Jill would eventually have to find the strength to cope with the heavy demands caused by Eva’s condition, what she’d have to set aside of her own aspirations and ambitions. I tried to comprehend that one day, unbearably, she’d have to bury a daughter of her own. But, most of all, I thought of the astonishing outpouring of love in that small, wooden chalet, of those lucky enough to have known Eva well, and whose lives were forever changed by her – not just friends and family, but her carers and NHS workers. This sharing of love is what truly matters, the only worthwhile legacy we leave behind. For this, despite her poor, damaged body and too-short life, I will forever remember Eva as a superhero. Chris Deerin is a leading journalist and commentator who heads independent, non-party think tank, Reform Scotland

Aug 28

City leaders urge employees to give blood

Albertville city employees will earn extra time off if they participate in a blood drive next week. During a city council meeting Monday night, Albertville City Councilmen granted additional vacation hours to any employee who participates in the annual Albertville vs. Boaz blood drive. The drive will he held Aug. 29 from 7 a.m. to 6 p.m. at the Albertville Depot, and at the Boaz Rec Center on Aug. 30 during the same hours. In other business, councilmembers also: • Postponed a public hearing for a request from Beck Holdings LLC to rezone property on South Broad Street from R-1 to R-8. The rezoning would allow the developer to build four garden homes on the property. However, nearby neighbors voiced concerns over increased traffic and having four driveways coming out onto the street in a small area, said Mayor Tracy Honea. “It will be easier to try to come to some type of resolution now while it is in the planning stages than it will be later on when construction starts,” he said. The closest cross street to the property is Bobo Street. The public hearing will be rescheduled. • Approved a resolution to purchase property at 319 White Oak Road at a cost of $200,000 for future expansion at the Albertville Regional Airport and authorized Honea to sign all necessary documents. • Approved a resolution for the Transportation Plan. The plan is part of the Rebuild Alabama Act. City leaders anticipate an allocation from the Rebuild Alabama Act fund of approximately $125,250 with increasing allocations for upcoming fiscal years. The funds received will be used to fund maintenance and improvement of city roads, including the resurfacing of Lexington Avenue, Vickie Drive and Northridge Trace. The council will next meet Sept. 11. The meeting was moved from its usual first Monday of the month due to the Labor Day holiday. The meeting begins at 6:30 p.m. in the Council Chambers at City Hall.

Aug 28

Modifiable risk factors found to be responsible for half of cardiovascular diseases

Credit: Pixabay/CC0 Public Domain Scientists of the Global Cardiovascular Risk Consortium under the auspices of the Department of Cardiology at the University Heart & Vascular Center of the Medical Center Hamburg-Eppendorf (UKE) and the German Center for Cardiovascular Research (DZHK) have proven that the five classic cardiovascular risk factors—excess weight, high blood pressure, high cholesterol, smoking, and diabetes mellitus—are directly connected to more than half of all cardiovascular diseases worldwide. High blood pressure is the most significant factor for the occurrence of heart attacks and strokes. The study’s results were published August 26 in the New England Journal of Medicine and are based on the data from 1.5 million persons from 34 countries. Cardiovascular diseases cause approximately a third of all deaths worldwide. They often develop silently over decades. Frequently without being recognized, the vascular walls change, giving rise to arteriosclerosis, in the wake of which coronary heart disease may occur, including complications such as heart attacks, acute cardiac death, or strokes. “Our study clearly shows that over half of all heart attacks and strokes are avoidable by checking and treating the classic risk factors. These results are of the highest significance for strengthening prevention in this area. At the same time, approximately 45% of all cardiovascular cases cannot be explained with these risk factors; they should motivate us and the academic funders to further research efforts,” says Professor Doctor Stefan Blankenberg, the medical director of the University Heart & Vascular Center at the UKE. The Global Cardiovascular Risk Consortium assessed the individual-level data of 1.5 million persons who took part in 112 cohort studies and originate from the eight geographical regions North America, Latin America, Western Europe, Eastern Europe and Russia, North Africa and the Middle East, Sub-Saharan Africa, Asia and Australia. The objective of the study was to gain a better understanding of the global distribution, the significance of the individual risk factors and their effects on cardiovascular diseases, and overall mortality in order to derive targeted preventive measures. “In principle, the five classic risk factors that we examined are modifiable, and thus responsive to preventive measures. So far, the proportion of preventable risk attributed to these five risk factors is still matter of debate,” lead author and associate professor Dr. Christina Magnussen, Department of Cardiology at the University Heart & Vascular Center of the UKE, explains. Regional differences in risk factors The study showed differences in the eight global regions regarding the frequency of the risk factors. The scientists saw the highest rates for overweight in Latin America, and the highest values for high blood pressure and high cholesterol in Europe. The risk factor smoking is particularly decisive in Latin America and Eastern Europe, diabetes mellitus in North Africa and in the Middle East. All five risk factors combined (excess weight, high blood pressure, high cholesterol, smoking, and diabetes mellitus) amount to 57.2% of women’s cardiovascular risk and to 52.6% of men’s. Thus, a substantial share of cardiovascular risk remains unexplained. In comparison, the five risk factors merely account for about 20% of the risk to die (overall mortality). Furthermore, the study also clearly shows a linear relation between high blood pressure, and high cholesterol, and the occurrence of cardiovascular diseases. The higher the values, the higher the likelihood of the occurrence of cardiovascular diseases. This result applies to all examined regions in the world. The scientists also identified a remarkable connection between cholesterol levels and overall mortality: Very low as well as high cholesterol levels increase overall mortality. The significance of all risk factors decreases with age; e.g., high blood pressure is more damaging to a 40 year old than an 80 year old. The body mass index (BMI) is the only exception and remains equally significant at any age. “This raises the question to which extent the target values for treating cardiovascular risk factors for the most elderly should be identical with those for the middle to older age bracket,” says Professor Blankenberg. Study identifies extensive range of starting points for preventive measures The study provides an extensive dataset to avoid cardiovascular diseases or reduce their effects for at-risk persons, or patients with cardiovascular diseases, by improving their lifestyle and by lowering blood pressure or cholesterol. “High systolic blood pressure accounts for the largest share of cardiovascular risk. We should place a particular focus on the therapy of patients with high blood pressure to avoid cardiovascular diseases as much as possible,” says associate professor Dr. Magnussen. More information: Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2206916 Provided by Universitätsklinikum Hamburg-Eppendorf Citation: Modifiable risk factors found to be responsible for half of cardiovascular diseases (2023, August 28) retrieved 28 August 2023 from https://medicalxpress.com/news/2023-08-factors-responsible-cardiovascular-diseases.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Aug 28

Dual-antiplatelet therapy should remain the standard strategy for PCI even in the drug-eluting stent era

Prasugrel monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents is not superior to dual-antiplatelet therapy (DAPT) for major bleeding but is non-inferior for cardiovascular events in patients with acute coronary syndrome (ACS) or high bleeding risk (HBR), according to late breaking research presented in a Hot Line session today at ESC Congress 2023. Very short (1 to 3 months) durations of DAPT followed by P2Y12 inhibitor monotherapy has been shown to reduce bleeding events without increasing cardiovascular events compared with standard durations of DAPT after PCI using drug-eluting stents. However, the incidence of major bleeding events within the 1-month mandatory DAPT period after PCI remains high in real clinical practice, particularly in patients with ACS or HBR. In single-arm studies, aspirin-free prasugrel or ticagrelor monotherapy following successful new-generation drug-eluting stent implantation was not associated with any stent thrombosis in selected low-risk patients with or without ACS. Removing aspirin from the DAPT regimen might reduce bleeding events early after PCI without compromising the risk of cardiovascular events. However, the efficacy and safety of this strategy has not been proven in randomized trials. ESC guidelines recommend 6 months of DAPT in HBR patients with ACS and 12 months of DAPT in non-HBR patients with ACS after PCI. In patients with non-ACS, 1 to 3 months of DAPT is recommended in HBR patients after PCI. STOPDAPT-3 investigated the efficacy and safety of aspirin-free prasugrel monotherapy compared with 1-month DAPT with aspirin and prasugrel in patients with ACS or HBR undergoing PCI with cobalt-chromium everolimus-eluting stents. From January 2021 to April 2023, the study enrolled 6,002 patients with ACS or HBR from 72 centers in Japan. Just before PCI, patients were randomized in a 1:1 fashion to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel after a loading dose of prasugrel 20 mg in both groups. There were two primary endpoints: 1) major bleeding events (defined as Bleeding Academic Research Consortium [BARC] type 3 or 5) at 1 month for superiority; and 2) cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month for non-inferiority. The major secondary endpoint was a composite of the co-primary bleeding and cardiovascular endpoints (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding) at 1 month representing net clinical benefit. The full analysis set population consisted of 5,966 patients (no-aspirin group: 2,984 patients; DAPT group: 2,982 patients). The average age was 71.6 years and 23.4% were women. At 1 month, the no-aspirin strategy was not superior to DAPT for the co-primary bleeding endpoint (4.47% vs. 4.71%; hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.75-1.20; p for superiority=0.66). The no-aspirin strategy was non-inferior to DAPT with a relative 50% margin for the co-primary cardiovascular endpoint (4.12% vs. 3.69%; HR, 1.12; 95% CI, 0.87-1.45; p for non-inferiority=0.01). Related Stories There was no between-group difference in the incidence of all-cause death (2.28% vs. 2.11% in the no-aspirin and DAPT groups, respectively). The major secondary endpoint occurred in 7.14% patients in the no-aspirin group and 7.38% patients in the DAPT group, with no between-group difference, indicating a similar effect on net clinical benefit for both groups. There was an excess of any coronary revascularisation (1.15% vs. 0.57%) and definite or probable stent thrombosis (0.71% vs. 0.44%) in the no-aspirin group compared with the DAPT group, while definite stent thrombosis was not different between the 2 groups (0.47% vs. 0.37%). In a subgroup analysis stratified by ACS and non-ACS, the excess risk of cardiovascular events in the no-aspirin group compared with the DAPT group was seen in patients with ACS, but not in those without ACS. The aspirin-free strategy compared with the DAPT strategy failed to reduce major bleeding within 1 month after PCI, but it was non-inferior for the co-primary cardiovascular endpoint with a relative 50% margin. Aspirin used for a limited period of 1 month after PCI as a component of DAPT might have exerted a protective effect on vulnerable coronary lesions, particularly in patients with ACS, without a large increase in major bleeding. DAPT should remain the standard strategy for PCI even in the new-generation drug-eluting stent era.” Dr. Masahiro Natsuaki, Study Author, Saga University, Japan European Society of Cardiology (ESC)

Aug 28

Komrokji Examines Differences Between the WHO and ICC MDS Criteria

Rami Komrokji, MD Although the current classification systems for patients with myelodysplastic syndromes (MDS) were able to identify groups of patients with similar outcomes, further refinement is needed to create more consistent criteria, according to findings from an international dataset analysis of the 2 classification systems presented by Rami Komrokji, MD, during the 2023 EHA Congress. “It’s clear that we are moving to a new era in the classification of MDS and that we have molecularly defined groups; those patients should be thought of, treated, and enrolled in clinical trials separately,” Komrokji said. “Then we have the morphologically defined groups, but we definitely need to step up, try to harmonize those [criteria], and go back into 1 classification that hematopathologists, clinicians, and clinical trialists use as a common language rather than having 2 different classifications.” The analysis, which was conducted on behalf of the International Consortium for MDS, used datasets from Moffitt Cancer Center and the European initiative GenoMed4all:GM encompassing 7017 patients with available molecular data to validate and compare the World Health Organization (WHO) and International Consensus Classification (ICC) 2022 classification criteria. Results showed that patients with deletion 5q (del5q) in the WHO (n = 107) and ICC groups (n = 108) from the Moffitt cohort both achieved an overall survival (OS) of 75.6 months vs 82.1 months for those from GenoMed4all:GM with del5q in the WHO (n = 219) and ICC groups (n = 223), respectively. Patients with SF3B1 mutations, which represent approximately 12% of all MDS cases, had the best outcomes compared with those with del5q and TP53-mutated disease. These patients in the WHO (n = 294) and ICC groups (n = 277) from the Moffitt cohort experienced an OS of 101.8 months and 111.6 months vs 104.9 months and 101.9 months in the GenoMed4all:GM WHO (n = 654) and ICC (n = 594) groups, respectively. In an interview with OncLive®, Komrokji, the vice chair of the Malignant Hematology Department and the head of the Leukemia and MDS Section at Moffitt Cancer Center in Tampa, Florida, discussed the comparative analysis as well as the next steps being taken to develop a more harmonized classification system. OncLive: What was the rationale behind the analysis presented at the 2023 EHA Congress? Komrokji: The classification for MDS has been evolving over the years, from FAB [French American British] in the 1980s, to different iterations from the WHO, but [for] the first time, in 2022 we have 2 classification systems: the WHO and the ICC. Both of them are an attempt to improve the classification for MDS, but also it creates a dilemma in the field and controversy regarding which one to follow. There are some differences [between the classification systems]. It was important to generate data-driven evidence to hopefully guide future harmonization of those 2 classifications. People are mixing classification vs prognostic models. Risk stratification in MDS is based on [the] Revised International Prognostic Scoring System [IPSS-R]. The classification historically is pathological classification [and] it should reflect a unique biology of the disease [as well as] unique groups that have a certain clinical phenotype [where] maybe the pathogenesis of defective hematopoiesis is similar in that group. We were trying to validate those and hopefully this is the first step in trying to come up with harmonization and [return to] 1 classification [system] in MDS. How was the analysis conducted? When the [ICC 2022] classification came out we looked at our database—we have a large database with more than 2500 patients fully annotated—and then we approached our colleagues in Europe. They kindly joined us with the GenoMed4all:GM MDS database, which is the MDS database for almost the whole [of] Europe. Advertisement Together, we were able to put approximately 7000 patients with MDS [into our platform], which is a very large cohort. Hopefully [it] will be a platform not only for this project, but for several other projects down the road. We reclassified all the patients according to the WHO and ICC [criteria], included only patients with fully annotated molecular data, and we looked at the questions that we wanted to address. What were the key findings of the analysis? The 2 classifications recognize molecularly-defined categories of MDS, namely SF3B1, del5q, as well as P53. There are slight differences in the definitions between both of them. For example, we demonstrated that SF3B1 is a unique category, approximately 12% to 13% of patients with MDS have very favorable outcomes with a median OS of more than 10 years [and] low chance of [dying from] leukemia. We also looked at a subset of patients [with] MDS with ring sideroblasts, which is usually the phenotype we see with SF3B1, but [we examined patients] if they were SF3B1 wild-type. That’s a smaller subset, approximately only 4% of patients, but they did not have the same favorable outcomes. The WHO retained [classification of] MDS with ring sideroblasts, which is probably something that could go away down the road in the future based on this. However, we have to think of those models in terms of generalizing them. In countries where there is no access to SF3B1 [testing], ring sideroblasts are still a good marker for SF3B1. We also confirmed that [the patient population with] del5q is a favorable group, [constituting] approximately 5% of patients [with MDS]. Bi-allelic TP53 [is found in] approximately 10% of patients [with MDS] and unfortunately they have very poor outcomes. The ICC proposed a different group of P53, monoallelic. If the blasts were more than 10%, they would consider that MDS/AML with P53. Those patients had worse outcomes and part of it is driven by the increased blast [percentage]. In the future, that category may go away, and we’ll probably stick more to the bi-allelic [characterization of] P53. In the morphologically defined [criteria], we showed that MDS ring sideroblasts without SF3B1 [mutations] are not different. The ICC proposed that the number of lineage dysplasia, whether we have multilineage vs single lineage dysplasia, does matter [and we showed that] multilineage dysplasia did worse.

Aug 28

USU set to compete in 20th annual blood battle against Weber State

Utah State University’s Aggies have donated enough blood to win the blood drive battle against Weber State University every year for the past 19 years — and USU isn’t planning on losing this year either, according to Bridger Esplin, the Aggie Red Cross student director. The event will take place from Sept. 5-8, and students and faculty can donate blood between 9 a.m. and 9 p.m. Not only is there a competitive aspect between USU and Weber, but all registered USU clubs, including sororities and fraternities, may receive prizes. But it’s not just the fact that USU has claimed victory for several decades — both universities’ donations have saved tens of thousands of lives. In the last 19 years, the blood battles have led to over 19,355 units of blood being donated, with each unit saving multiple lives, according to Kirsten Stuart, the communications and public affairs associate with the American Red Cross. “I think service should be a huge part of any student’s experience at college, and this is just a really great opportunity for students to get involved,” said Tyson Packer, the student advocate vice president for Utah State University Student Association. While the competitive aspect is certainly enjoyable for many students, Stuart said “the blood donations are important regardless of the situation,” especially with sharp declines in summer donors. “In the summer, the blood supply does go down because people are out more, they’re out doing more things and quite frankly, some people are getting hurt more and needing blood — but the donations are down,” Stuart continued. “This specific blood battle is an amazing way to help in replenishing that supply.” Utah’s blood donations don’t just help Utahns. USU’s blood battles are crucial in helping surgery patients and those recovering from disasters from all over the country. “Utah powers a lot of the country,” Esplin said. Blood donations could especially help victims of natural disasters, from wildfires in Maui, Hawaii to Hurricane Hilary’s impact on the U.S.’s West Coast, according to Nelda Ault-Dyslin, the assistant director of community-engaged learning at the USU Center for Community Engagement. Participants can observe where their donations may travel to on the Red Cross website or app and can even receive a letter of thanks stating which hospital their blood went to, as well as how it helped save a life, Stuart said. For students that are squeamish with needles, they can either volunteer with the Red Cross professionals or at the Blood Battle itself, Esplin said. Still, donating blood is still one of the most effective ways to make a difference. Despite Esplin’s original fears when he first donated, he felt confident afterward. “It actually wasn’t nearly as bad as I thought,” he said. Packer said students who may not understand the purpose of donating blood should ask the Red Cross volunteers about what their blood will do for other people. “They’ll tell you personal stories about people who have gotten blood transfusions, about EMTs who have had to get blood transfusions or have saved lives at car accidents that they’ve been called to,” Packer said. “I just tell students to get in there, ask around, hear about those personal experiences and it’ll really open their eyes to why it’s so important.” For Stuart, donating blood is about just that. When her mother had a gastrointestinal bleed and needed a blood transfusion, she said she found herself getting emotional after seeing the American Red Cross blood donation bags. “Quite frankly, all of us at some point are going to be touched by someone who needed a blood donation,” Stuart said. “I want them (students) to really realize the huge difference that they are making in so many people’s lives with their blood donation. Whether they’re saving the lives of an infant, a child, you know, someone’s mother, grandmother — that literal act of 30 minutes to an hour of their time can mean years to somebody else that they get with a family member.” Previous Article Women’s soccer falls to Utes on late goal

Aug 28

China to stop requiring negative COVID-19 test from incoming travelers

TAIPEI, Taiwan (AP) — China will no longer require a negative COVID-19 test result for incoming travelers starting Wednesday, a milestone in its reopening to the rest of the world after a three-year isolation that began with the country’s borders closing in March 2020. Foreign Ministry spokesperson Wang Wenbin announced the change at a briefing in Beijing on Monday. China in January ended quarantine requirements for its own citizens traveling from abroad, and over the past few months has gradually expanded the list of countries that Chinese people can travel to and increased the number of international flights. READ MORE: Severe floods in China killed 29 and caused tens of billions of economic losses Beijing ended its tough domestic “zero COVID” policy only in December, after years of draconian curbs that at times included full-city lockdowns and lengthy quarantines for people who were infected. The restrictions slowed the world’s second-largest economy, leading to rising unemployment and occasional instances of unrest. As part of those measures, incoming travelers were required to isolate for weeks at government-designated hotels. Residents were in some cases forcibly locked into their homes in attempts to stop the virus from spreading. Protests in major cities including Beijing, Shanghai, Guangzhou and Nanjing erupted in November over the COVID curbs, in the most direct challenge to the Communist Party’s rule since the Tiananmen protests of 1989. In early December, authorities abruptly scrapped most COVID controls, ushering in a wave of infections that overwhelmed hospitals and morgues. A U.S. federally funded study this month found the rapid dismantling of the “zero COVID” policy may have led to nearly 2 million excess deaths in the following two months. That number greatly exceeds official estimates of 60,000 deaths within a month of the lifting of the curbs. During the years of “zero COVID,” local authorities occasionally imposed snap lockdowns in attempts to isolate infections, trapping people inside offices and apartment buildings. READ MORE: China’s Xi calls for measures to mitigate flooding amid economic downturn From April until June last year, the city of Shanghai locked down its 25 million residents in one of the world’s largest pandemic-related mass lockdowns. Residents were required to take frequent PCR tests and had to rely on government food supplies, often described as insufficient. Throughout the pandemic, Beijing touted its “zero COVID” policy — and the initial relatively low number of infections — as an example of the superiority of China’s political system over that of Western democracies. Since lifting the COVID curbs, the government has been contending with a sluggish economic recovery. The restrictions, coupled with diplomatic frictions with the United States and other Western democracies, have driven some foreign companies to reduce their investments in China. Associated Press news assistant Caroline Chen in Beijing contributed to this report.

Aug 28

Hypoxia and panvascular diseases: exploring the role of hypoxia-inducible factors in vascular smooth muscle cells under panvascular pathologies

image: In the panvascular system, hypoxia-inducible factors (HIFs) can lead to excessive activity of vascular smooth muscle cells (VSMCs), presenting a phenotype of proliferation and migration in atherosclerosis and pulmonary arterial hypertension. In atherosclerosis, VSMCs influenced by HIFs may also exhibit a myofibroblast-like transformation, whereas in pulmonary arterial hypertension, noteworthy electrophysiological changes occur in HIF-affected VSMCs. In the aortic aneurysm, HIFs are associated with apoptosis and vascular remodeling in VSMCs. Regarding vascular calcification, HIFs are related to osteochondral differentiation in VSMCs. view more Credit: ©Science China Press This study is led by Prof. Junbo Ge (Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases), Prof. Hua Li (Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases), and Prof. Hao Lu (Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases). As an emerging concept, panvascular diseases encompass a group of cardiovascular disorders characterized mainly by atherosclerosis, involving crucial organs such as the heart, brain, kidneys, and limbs. Hypoxia-inducible factor (HIF) plays a pivotal role as a major regulatory factor in the cardiovascular system’s response to common stressors, such as hypoxia. Meanwhile, vascular smooth muscle cells (VSMCs) serve as key cells responsible for regulating cardiovascular system pressure and oxygen delivery. The plasticity, versatility, and interaction of these two factors with panvascular diseases warrant in-depth investigation. In the pathological state of panvascular diseases, overactive VSMCs (e.g., in atherosclerosis, pulmonary arterial hypertension) or dysfunctional VSMCs (e.g., in arterial aneurysms, vascular calcification) are closely associated with HIFs. These widespread systemic diseases also underscore the interdisciplinary nature of panvascular medicine. Furthermore, considering the similarities in proliferative characteristics between VSMCs and cancer cells, as well as the delicate balance between angiogenesis and cancer progression, there is an urgent need for more precise regulatory targets or combination therapies to enhance the effectiveness of HIF-targeted treatments. Based on the above content, this review focuses on discussing the significance of the HIF signaling pathway in panvascular diseases related to VSMCs, taking into consideration the importance of balancing global and local, as well as temporal and spatial aspects. The review also explored the relevance of HIF-related drugs’ targets in panvascular diseases while weighing their pros and cons. The “-dustats” is a novel type of drug that can inhibit PHD, thus activating the HIF-EPO pathway, and its effect on increasing EPO in the body is gentle. In existing research, the drug “-dustats” has been found to improve iron metabolism while treating anemia, and it generally does not exhibit significant cardiovascular side effects or promote cancer occurrence. Furthermore, more precise and targeted HIF pathway-activating drugs require either more specific indirect activation of HIF (e.g., inhibitors targeting specific PHD1-3 or FIH) or more effective direct activation targeting the specific HIF isoforms. Additionally, the issue of drug resistance also needs to be addressed. Collectively, there are three key points in advancing the transformation of HIF-related treatment strategies for VSMC in panvascular medicine: (1) focusing on the commonality and specificity of HIFs in panvascular disease; (2) the overall consideration of targeting HIF-related pathways, and (3) the development of precise drugs targeting HIF-related pathways. Overall, the clinical transformation of HIFs-related therapies requires that doctors pay more attention to individual differences (eg, place of residence, gender, and disease) in diagnosis and treatment to identify underlying problems; researchers explore and clarify the different roles and interactions of HIFs in different organs/systems or different stages of the disease; and pharmaceutical experts or engineers strive to industrialize the production of personalized targeted drugs with superior pharmacodynamics and pharmacokinetics. Therefore, based on the principle of “from doctors, by engineers/researchers, for patients”, the substantial clinical transformation of HIFs-related treatment in panvascular medicine can be realized. Journal Science Bulletin Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.