New Findings on Clopidogrel and CABG: 3-Day Gap Before Surgery Matches 5-Day Wait for Safety

USA: In a recent study published in The Annals of Thoracic Surgery, researchers explored the effects of preoperative clopidogrel on the outcomes of isolated coronary artery bypass grafting (CABG). This analysis provides new insights into the role of clopidogrel, a commonly used antiplatelet medication, in CABG surgery.

The study found that undergoing CABG within five days of clopidogrel use is linked to a modest rise in operative mortality and the need for re-exploration due to bleeding, as well as a significant increase in blood product utilization.

“The risks associated with clopidogrel decrease as the interval between discontinuation and surgery lengthens, stabilizing after three days. Consequently, performing CABG three days post-clopidogrel offers similar outcomes to waiting five days, potentially shortening the optimal waiting period,” Juan A. Crestanello, Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, and colleagues wrote.

Clopidogrel is frequently administered to patients undergoing cardiovascular procedures to prevent thrombotic events. Its use before CABG is intended to reduce the risk of postoperative complications such as graft occlusion and myocardial infarction. The researchers aimed to analyze the Society of Thoracic Surgeons Database to investigate risks and optimal timing for coronary artery bypass graft after clopidogrel administration.

For this purpose, patients were grouped according to their use of clopidogrel within five days before surgery and further divided based on the number of days since their last dose (ranging from 0 to 5 days). The control group consisted of patients who did not receive clopidogrel within five days of the operation.

The primary outcome measured was operative mortality, while secondary outcomes included the need for mediastinal re-exploration due to bleeding and the amount of blood products used.

The following were the key findings of the study:

  • Among 148,317 isolated CABG, 13.2% received clopidogrel within five days.
  • Minimal differences in operative mortality (2.8% versus 2.1%), higher rates of mediastinal re-exploration (3.5% versus 2.1%), and blood product utilization (72.7% versus 56.8%) were in the clopidogrel group.
  • The adjusted odds ratio of operative mortality peaked on the day of clopidogrel administration but was comparable to controls after that.
  • The odds of re-exploration were highest on day 0, decreasing gradually to a plateau after day 3.
  • Patients operated on day 3 after clopidogrel administration had similar odds of operative mortality and mediastinal re-exploration for bleeding and shorter total and preoperative length of stays but higher blood product utilization compared to day 5.

CABG within five days from clopidogrel — increased bleeding, mortality, transfusion, risk of mortality, and bleeding decreases over time, plateauing after three days, the researchers concluded.

Reference:

Choi, K., Schaff, H. V., Villavicencio, M. A., Dearani, J. A., Stulak, J. M., Greason, K. L., Spadaccio, C., Todd, A., & Crestanello, J. A. (2024). Effect of preoperative clopidogrel on outcomes of isolated coronary artery bypass graft. The Annals of Thoracic Surgery. https://doi.org/10.1016/j.athoracsur.2024.07.013

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Common lab tests not reliable for diagnosing Long COVID, finds study

A new study found that most routine laboratory tests are not reliable for diagnosing Long COVID, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC).

The study, published in Annals of Internal Medicine, found no reliable biomarker among 25 routine clinical laboratory values for prior infection, PASC or specific types of PASC clusters. This suggests none of these routine labs can serve as a clinically useful biomarker of PASC.

“Our study shows patients can have severe Long COVID with normal lab results. This suggests doctors should not focus on the results of blood panels to diagnose Long COVID but should focus more on symptoms and ways to help patients get relief by treating their symptoms,” said the study’s first author, Kristine Erlandson, MD, a professor in the Division of Infectious Diseases at the University of Colorado Anschutz Medical Campus.

Seven percents of all adults in the U.S., nearly 18 million people, currently have long COVID, according to Agency for Healthcare Research and Quality’s Medical Expenditure Panel Survey.

“Our challenge is to discover biomarkers that can help us quickly and accurately diagnose long COVID to ensure people struggling with this disease receive the most appropriate care as soon as possible,” said David Goff, MD, PhD, director for the Division of Cardiovascular Sciences at the NIH’s National Heart, Lung, and Blood Institute. “Long COVID symptoms can prevent someone from returning to work or school, and may even make everyday tasks a burden, so the ability for rapid diagnosis is key.”

This study was funded by National Institutes of Health’s (NIH) Researching COVID to Enhance Recovery (RECOVER) Initiative. The RECOVER initiative includes multiple research studies that involve thousands of participants from across the country. In Colorado, these studies take place in the Colorado Clinical and Translational Sciences Institute (CCTSI) at CU Anschutz.

To investigate clinical laboratory markers of SARS-CoV-2 and PASC, the researchers examined data from nearly 10,000 adults with and without SARS-CoV-2 infection. The researchers recruited from over 80 enrolling sites across 33 U.S. states plus Washington, DC and Puerto Rico, making it one of the largest and most diverse studies of its kind.

The study compared results in several ways: between participants with and without prior SARS-CoV-2 infection at six months after infection, between participants with and without PASC and between participants with each of four most common PASC symptom phenotypes and those unlikely to have PASC.

They found participants with prior SARS-CoV-2 infection showed modest increases in HbA1c (a marker of long-term blood sugar levels) and urinary albumin-to-creatinine ratio (uACR), along with small decreases in platelet counts.

“While these differences are statistically significant, these associations are generally small and not reliable enough to serve as diagnostic biomarkers for PASC,” Erlandson says.

The researchers suggest this data shows the complexity of PASC as a condition that may involve multiple physiological pathways beyond simple laboratory markers, such as those for inflammation, anemia or other markers.

“Long COVID has been very elusive; numerous possible symptoms, no definite cause and no clear treatment. We hear from patients that their concerns are dismissed by providers because their lab tests are normal. In this study, even the exhaustive list of routine blood tests could not help in making a PASC diagnosis. This is an important observation in PASC research as prior smaller studies showed inconsistent abnormalities in some blood tests. Until a reliable biomarker is found, the best diagnostic modality for PASC remains the old-fashioned history taking and clinical assessment,” Grace McComsey, MD, senior author of the paper, professor and vice dean of clinical and translational research at Case Western Reserve University.

The researchers also note that it’s still important to do routine laboratory tests to rule out other conditions during the process of diagnosing PASC.

Reference:

 Kristine M. Erlandson, Linda N. Geng, Caitlin A. Selvaggi, Tanayott Thaweethai, Peter Chen, Nathan B. Erdmann, Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort, Annals of Internal Medicine,  https://doi.org/10.7326/M24-0737.

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Ketogenic Diet reduces friendly gut bacteria and raises cholesterol levels, suggests study

Published in Cell Reports Medicine, the research from the Centre for Nutrition, Exercise, and Metabolism involved 53 healthy adults for up to 12 weeks. Participants followed either a moderate sugar diet (control), a low-sugar diet (less than 5% of calories from sugar), or a ketogenic (keto) low-carbohydrate diet (less than 8% of calories from carbohydrates).

Key findings include:

• Increased Cholesterol: The keto diet raised cholesterol levels, particularly in small and medium sized LDL particles. The diet increased apolipoprotein B (apoB), which causes plaque buildup in arteries. In contrast, the low-sugar diet significantly reduced cholesterol in LDL particles.

• Reduced Favourable Gut Bacteria: The keto diet altered gut microbiome composition, notably decreasing Bifidobacteria, beneficial bacteria often found in probiotics. This bacteria has wide ranging benefits: producing b vitamins, inhibiting pathogens and harmful bacteria and lowering cholesterol. Sugar restriction did not significantly impact the gut microbiome composition.

• Glucose Tolerance: The keto diet reduced glucose tolerance, meaning the adults’ bodies became less efficient at handling carbohydrates.

• Both Diets Resulted In Fat Loss: Keto Diet resulted in an average of 2.9 kg fat mass loss per person, whilst the sugar restricted diet followed with an average 2.1 kg fat mass loss per person at 12 weeks.

• Metabolism: Researchers also noticed that the keto diet caused significant changes in lipid metabolism and muscle energy use, shifting the body’s fuel preference from glucose to fats.

• Physical Activity Levels: Both sugar restriction and keto diets achieved fat loss without changing physical activity levels. Previous studies from the Centre for Nutrition, Exercise and Metabolism have shown that skipping breakfast or intermittent fasting cause reductions in physical activity.

Lead researcher Dr. Aaron Hengist highlighted the concerning cholesterol findings:

“Despite reducing fat mass, the ketogenic diet increased the levels of unfavourable fats in the blood of our participants, which, if sustained over years, could have long-term health implications such as increased risk of heart disease and stroke.”

Dr. Russell Davies, who led the microbiome research, explained the impact on gut health:

“Dietary fibre is essential for the survival of beneficial gut bacteria like Bifidobacteria. The ketogenic diet reduced fibre intake to around 15 grams per day, half the NHS recommended intake. This reduction in Bifidobacteria might contribute to significant long-term health consequences such as an increased risk of digestive disorders like irritable bowel disease, increased risk of intestinal infection and a weakened immune function.”

Professor Javier Gonzalez, who oversaw the research, commented on the glucose findings:

“The ketogenic diet reduced fasting glucose levels but also reduced the body’s ability to handle carbs from a meal. By measuring proteins in muscle samples taken from participants’ legs, we think this is probably an adaptive response to eating less carbohydrates day-to-day and reflects insulin resistance to storing carbs in muscle. This insulin resistance is not necessarily a bad thing if people are following a ketogenic diet, but if these changes persist when people switch back to a higher carbohydrate diet it could increase the risk of developing type 2 diabetes in the long-term”

In light of this new research, the academics conclude that if you’re considering a diet, a low sugar one will be better for most people. More work is needed to understand how individuals may benefit from each type of diet. The government recommends that free sugars (those added to food or drink or found naturally in honey, syrups, fruit juices and smoothies) should be restricted to less than 5% of total energy intake. Professor Dylan Thompson, who also oversaw the work, said:

“The ketogenic diet is effective for fat loss, but it comes with varied metabolic and microbiome effects that may not suit everyone. In contrast, sugar restriction supports government guidelines for reducing free sugar intake, promoting fat loss without apparen­­t negative health impacts.”

Reference:

Aaron Hengist, Russell G. Davies, Jean-Philippe Walhin, Françoise Koumanov, Dylan Thompson Javier T. Gonzalez, Ketogenic diet but not free-sugar restriction alters glucose tolerance, lipid metabolism, peripheral tissue phenotype, and gut microbiome: RCT, Cell Reports Medicine, DOI:https://doi.org/10.1016/j.xcrm.2024.101667.

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Text-Message Program effective way to quit smoking in adolescents, unravels JAMA study

USA: A
targeted, interactive text message intervention increased self-reported vaping
cessation rates among adolescents who used to smoke, a study finds

The 2-group
randomized clinical trial published in the journal JAMA Network indicates that when a targeted, interactive text
message intervention was implemented which leads to to increased self-reported
vaping cessation rates among those recruited through social media channels.

E-cigarettes are the most popular tobacco product
among adolescents. Even though the dangers of nicotine for teens are well
known, there are no proven programs to help them quit smoking.

To execute such an intervention a 2-group, double-blind, individually randomized
clinical trial was conducted by Amanda L. Graham, PhD, Innovations Center, Truth
Initiative, Washington, DC and colleagues, where they recruited 1503 adolescent
e-cigarette users via social media ads, with follow-ups at 1 and 7 months after
randomization was conducted from October 1, 2021, to October 18, 2023. The
intervention was provided through text messages, with assessments completed
either online or over the phone.

Participants were U.S. residents aged 13 to 17 who had
used e-cigarettes in the past 30 days, were interested in quitting within the
next 30 days and owned a mobile phone with an active texting plan.

All participants received monthly text message assessments regarding their
e-cigarette use. The assessment-only control group (n = 744) received only text
messages related to study retention.

The main outcome measured was self-reported 30-day abstinence from vaping at
7 months, analyzed using an intention-to-treat approach, where missingness
coded as vaping.

The result revealed that:

  • The 7-month follow-up rate was 70.8%.
  • Point-prevalence abstinence rates were
    37.8% among intervention participants and 28.0% among control
    participants (relative risk, 1.35).

“The text-message
program was found to be effective in encouraging teenagers to quit recognizing
that this age group is still in a critical growth stage where exposure to
tobacco and smoke can negatively impact their development.,” said the researchers.

Reference: Graham AL, Cha S, Jacobs MA, et al. A Vaping Cessation Text
Message Program for Adolescent E-Cigarette Users: A
Randomized Clinical Trial. JAMA. Published online
August 07, 2024. doi:10.1001/jama.2024.11057

 

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Subdural irrigation and burr-hole drainage may reduce complications in hematoma patients, finds research

A new study published in the journal of The Lancet found that the patients who had burr-hole drainage with subdural irrigation had lower reoperation rates and similar functional results when compared to patients without subdural irrigation.

One common intracranial emergency that is surgically treated is chronic subdural hemorrhage. In order to remove a chronic subdural hematoma, a burr hole must be created for access, the subdural region must be irrigated and a subdural drain must be inserted. Despite the subdural drain has been developed as advantageous, the curative effect of subdural irrigation has not been explored. Therefore, Rahul Raj and colleagues did this study in order to investigate the efficiency of subdural irrigation in Chronic subdural hematoma.

The FINISH experiment was conducted over 5 neurosurgery centers in Finland that included persons over 18 years of age with a persistent subdural hematoma needing burr-hole drainage. The patients were randomly allocated (1:1) by computer-generated block randomisation with block sizes of 4, 6, or 8 stratified by location, to burr-hole drainage either with or without subdural irrigation. A burr hole was drilled at the site of greatest hematoma thickness in both groups, and the subdural space was either drained or not before inserting a subdural drain that was left in place for 48 hours. The percentage of reoperations within 6 months was the main outcome measured and a non-inferiority margin of 7·5% was established. Important secondary outcomes that were also necessary to determine non-inferiority included the percentage of patients who had poor functional results and the 6-month death rate.

This study evaluated 1644 patients between January 1, 2020 and August 17, 2022, to determine their eligibility. Of these individuals, 589 (or 36%) were treated and randomly allocated to a therapy group. The 6-month duration of follow-up was prolonged till February 14, 2023. 54 (18·3%) out of 295 patients in the group allocated to receive no irrigation and 37 (12·6%) out of 294 participants in the group assigned to receive irrigation were found to require reoperation in the intention-to-treat analysis.

The mortality rate and the percentage of individuals with a modified Rankin Scale score of 4-6 did not differ significantly across the groups. The systemic infections, cerebral hemorrhage, and epileptic seizures were the most common serious adverse events. Overall, the experiment supports the use of subdural irrigation because there were no variations in functional outcome or death between the groups.

Reference:

Raj, R., Tommiska, P., Koivisto, T., Leinonen, V., Danner, N., Posti, J. P., Laukka, D., Luoto, T., Rauhala, M., Tetri, S., Korhonen, T. K., Satopää, J., Kivisaari, R., Luostarinen, T., Schwartz, C., Czuba, T., Taimela, S., Lönnrot, K., Järvinen, T. L. N., … Zeiler, F. A. (2024). Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial. In The Lancet (Vol. 403, Issue 10446, pp. 2798–2806). Elsevier BV. https://doi.org/10.1016/s0140-6736(24)00686-x

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Kidney stones not independently linked to chronic kidney disease, suggests study

A new study published in the Journal of American Society of Nephrology found that kidney stones were not independently linked to chronic kidney disease (CKD). Around 5 and 13% of adults suffer from kidney stones and chronic kidney disease, respectively. Renal crystal deposition, or nephrocalcinosis, can cause progressive loss of GFR and end-stage renal disease (ESRD) at a young age. Rare inherited illnesses such as primary hyperoxaluria, 2-8-hydroxyadenine crystalluria, Dent disease, and cystinuria can cause CKD which is a documented consequence of kidney stones.

Kidney stones may be a contributing factor in the development and progression of CKD even though the incidence of ESRD directly linked to kidney stones is estimated to be 3.2% among patients starting continuous hemodialysis. The precise association between previous kidney stones and increased CKD risk is yet unknown, despite observational studies suggesting such a possibility. Therefore, Zhou LT and team conducted this study to find out the intricate relationship between kidney stones and CKD.

Unbiased screening was employed to find shared comorbidities between two illnesses. Genetic association studies across a range of variables were conducted after obtaining genome-wide association study summary results from the UK Biobank (UKBB), CKDGen, and FinnGen. To identify causal relationships, bidirectional Mendelian randomization (MR) studies were carried out. Multivariable MR was also employed, which encompassed the common comorbidities such as obesity, diabetes, and hypertension. Using a UKBB subgroup and cohorts from the Mayo Clinic, observational analyses were conducted.

There was not a significant genetic association found between kidney stones and chronic kidney disease (CKD), despite the identification of 123 illnesses as shared comorbidities. Kidney stones and the risk of CKD were not significantly correlated, according to an unadjusted MR analysis. Although there was a significant correlation between kidney stones and a higher urine albumin-creatinine ratio (UACR), this correlation vanished in the multivariable MR model. Moreover, a robust regression model did not find an independent link between kidney stones and UACR or eGFR in a cross-sectional study restricted to the UKBB sample.

However, in multivariable MR models, CKD was linked to a lower the incidence of renal stones. Additionally, decreased eGFR was linked to reduced urine calcium excretion and urinary calcium oxalate/phosphate supersaturation in the Mayo Clinic cohort with accessible urinary biochemistries. Overall, kidney stones and CKD were not shown to be correlated in this study. On the other hand, CKD was linked to a lower incidence of kidney stones made of calcium, most likely as a result of altered vital signs of the urine, such as decreased excretion of calcium.

Reference:

Zhou, L.-T., Ali, A. E., Jayachandran, M., Haskic, Z., Harris, P. C., Rule, A. D., Koo, K., McDonnell, S. K., Larson, N. B., & Lieske, J. C. (2024). Association between Kidney Stones and CKD. In Journal of the American Society of Nephrology. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1681/asn.0000000000000453

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Physical Function as Key Factor in Fracture Risk for Older Women with Type 2 Diabetes: JAMA

Sweden: A recent study published in JAMA Network Open has attributed higher fracture risk among older women with type 2 diabetes to physical function rather than skeletal characteristics. 

“In the cohort study of 3,008 older women, including 294 with type 2 diabetes, T2D was linked to higher fracture risk and improved bone mineral density (BMD) and microarchitecture but did not affect bone material strength. However, physical function was notably impaired in those with T2D,” the researchers reported.

The reasons for the increased fracture risk in T2D are not fully understood. Considering this, Michail Zoulakis, Sahlgrenska Osteoporosis Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden, and colleagues aimed to determine if worse physical function or poorer skeletal characteristics explain the increased fracture risk in T2D.

For this purpose, the researchers conducted a prospective observational study utilizing the Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures cohort, focusing on older women in the Gothenburg area from March 2013 to May 2016. Incident fracture data was followed up until March 2023, with data analysis conducted from June to December 2023.

Participants’ exposure data were gathered through questionnaires, as well as measurements of anthropometrics, physical function, and bone density using dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral computed tomography (HR-pQCT). A subset of participants also underwent bone microindentation to evaluate the bone material strength index (BMSi).

The primary outcomes included baseline assessments of bone characteristics and physical function and radiographically verified incident fractures.

The following were the key findings of the study:

  • Of 3008 women aged 75 to 80 years, 294 women with T2D (mean age, 77.8 years) were compared with 2714 women without diabetes (mean age, 77.8 years).
  • Women with T2D had higher BMD at all sites (total hip, 4.4% higher; femoral neck (FN), 4.9% higher; and lumbar spine, 5.2% higher) than women without.
  • At the tibia, women with T2D had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction.
  • There was no difference in BMSi (T2D mean, 78.0 versus controls, 78.1).
  • Women with T2D had lower performance on all physical function tests.
  • The study found 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes.
  • During a median follow-up of 7.3 years, 1071 incident fractures, 853 major osteoporotic fractures (MOF), and 232 hip fractures occurred.
  • In adjusted (for age, body mass index, clinical risk factors, and FN BMD) Cox regression models, T2D was associated with an increased risk of any fracture (HR, 1.26) and MOF (HR, 1.25).

“The findings suggest that type 2 diabetes is linked to higher BMD and improved bone microarchitecture, with no difference in bone material strength index (BMSi). However, T2D was also associated with reduced physical function, indicating that diminished physical ability is likely the primary factor contributing to the increased fracture risk observed in women with T2D,” the researchers concluded.

Reference:

Zoulakis M, Johansson L, Litsne H, Axelsson K, Lorentzon M. Type 2 Diabetes and Fracture Risk in Older Women. JAMA Netw Open. 2024;7(8):e2425106. doi:10.1001/jamanetworkopen.2024.25106

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Early ovary removal tied to brain changes: Study highlights risks for women considering premenopausal bilateral oophorectomy

USA: Research published in Alzheimer’s & Dementia reveals that MRI scans indicate reduced white matter integrity in multiple brain regions among women who undergo ovarian removal before menopause.

“Women who underwent bilateral oophorectomy before age 40 experienced decreased white matter integrity in various brain regions later in life. These findings are significant for women contemplating this procedure for noncancerous conditions,” the researchers reported.

Premenopausal bilateral oophorectomy involves the surgical removal of both ovaries before natural menopause occurs. It is often performed to mitigate the risk of ovarian cancer or manage other noncancerous gynecological conditions. PBO is associated with later-life cognition, but there is no clarity on the underlying brain changes. Considering this, Michelle M. Mielke, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA, and colleagues sought to assess the impact of PBO and PBO age on white matter integrity.

The study included females with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) (22 with PBO < 40 years; 39 with PBO 46-49 years; 43 with PBO 40-45 years; 907 referents without PBO < 50 years). Linear regression models were adjusted for age and apolipoprotein E (APOE) genotype.

The researchers reported the following findings:

  • Females with PBO < 40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus callosum, inferior frontal-occipital fasciculus, superior occipital, and superior temporal white matter.
  • Adjusting for estrogen replacement therapy use did not attenuate results.
  • Females who underwent PBO between 45 and 49 also had some changes in white matter integrity.

The researchers concluded, “Abrupt sex hormone changes due to PBO, especially < 40 years, are tied to lower white matter integrity in later life. A larger group of participants followed over an extended period is crucial to better understand the alterations in white matter and to establish how these changes relate to cognitive decline.”

They noted that the women involved in this study utilized conjugated equine estrogens, and it remains unclear whether alternative forms of estrogen replacement therapy (ERT) could offer greater benefits in preserving white matter integrity in the brain later in life.

Reference:

Mielke MM, Frank RD, Christenson LR, Reid RI, Fields JA, Knyazhanskaya ZE, Kara F, Vemuri P, Rocca WA, Kantarci K. Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life. Alzheimers Dement. 2024 Jun 20. doi: 10.1002/alz.13852. Epub ahead of print. PMID: 38899634.

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Dual action antibiotic could make bacterial resistance nearly impossible, suggests study

A new antibiotic that works by disrupting two different cellular targets would make it 100 million times more difficult for bacteria to evolve resistance, according to new research from the University of Illinois Chicago.

For a new paper in Nature Chemical Biology, researchers probed how a class of synthetic drugs called macrolones disrupt bacterial cell function to fight infectious diseases. Their experiments demonstrate that macrolones can work two different ways – either by interfering with protein production or corrupting DNA structure.

Because bacteria would need to implement defenses to both attacks simultaneously, the researchers calculated that drug resistance is nearly impossible.

“The beauty of this antibiotic is that it kills through two different targets in bacteria,” said Alexander Mankin, distinguished professor of pharmaceutical sciences at UIC. “If the antibiotic hits both targets at the same concentration, then the bacteria lose their ability to become resistant via acquisition of random mutations in any of the two targets.”

Macrolones are synthetic antibiotics that combine the structures of two widely used antibiotics with different mechanisms. Macrolides, such as erythromycin, block the ribosome, the protein manufacturing factories of the cell. Fluoroquinolones, such as ciprofloxacin, target a bacteria-specific enzyme called DNA gyrase.

Two UIC laboratories led by Yury Polikanov, associate professor of biological sciences, and Mankin and Nora Vázquez-Laslop, research professor of pharmacy, examined the cellular activity of different macrolone drugs.

Polikanov’s group, which specializes in structural biology, studied how these drugs interact with the ribosome, finding that they bind more tightly than traditional macrolides. The macrolones were even capable of binding and blocking ribosomes from macrolide-resistant bacterial strains and failed to trigger the activation of resistance genes.

Other experiments tested whether the macrolone drugs preferentially inhibited the ribosome or the DNA gyrase enzymes at various doses. While many designs were better at blocking one target or another, one that interfered with both at its lowest effective dose stood out as the most promising candidate.

“By basically hitting two targets at the same concentration, the advantage is that you make it almost impossible for the bacteria to easily come up with a simple genetic defense,” Polikanov said.

The study also reflects the interdisciplinary collaboration at the UIC Molecular Biology Research Building, where researchers from the colleges of medicine, pharmacy and liberal arts and sciences share neighboring laboratories and drive basic science discoveries like this one, the authors said.

“The main outcome from all of this work is the understanding of how we need to go forward,” Mankin said. “And the understanding that we’re giving to chemists is that you need to optimize these macrolones to hit both targets.” 

Reference:

Aleksandrova, E.V., Ma, CX., Klepacki, D. et al. Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-024-01685-3.

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ADHD symptoms in autistic children linked to neighborhood conditions, claims study

Autistic youth who were born in underserved neighborhoods are more likely to have greater attention deficit hyperactivity disorder (ADHD) symptoms than those born in communities with more resources. This is one finding of a new study led by researchers at the UC Davis MIND Institute.

This is the first time researchers have investigated how neighborhood factors are associated with ADHD in autistic and non-autistic children. The study provides new insights into mental health conditions and has the potential to inform public policy changes to improve health equity.

It was published in the journal JCPP Advances.

“We found that some neighborhood factors are strongly related to ADHD symptoms in autistic children,” said Catrina Calub, the first author on the paper. Calub is a postdoctoral researcher in the laboratory of Julie Schweitzer, a professor in the Department of Psychiatry and Behavioral Sciences and the MIND Institute.

“In this study, we didn’t find this effect in typically developing kids or in kids with other developmental disabilities, only in the autistic children. It suggests that when autistic kids live in neighborhoods with fewer resources, they tend to have more pronounced ADHD symptoms,” Calub said.

ADHD symptoms can include higher rates of inattention, hyperactivity and impulsive behavior.It is associated with:

• Challenges in school performance and relationships with friends

• Lower self-esteem and greater risk for anxiety and depression

• Higher potential for substance use disorders and accidents

• Emotional dysregulation and conduct problems

Study expands findings from long-term research

The researchers used data from two studies: the decades-long Childhood Autism Risks from Genetics and the Environment (CHARGE) study led by Irva Hertz-Picciotto at the MIND Institute and the ReCHARGE follow-up project.

CHARGE and ReCHARGE assess how genetics, environment and other factors affect development from early childhood (2–5 years) through adolescence (8-20 years).

The team looked at 246 autistic children, 85 with developmental delays (without autism), and 193 who were neurotypical. Then, they applied the Child Opportunity Index, which uses census data to track over 30 neighborhood traits. These traits include socioeconomics, green space, single-parent households and concentration of early childhood education centers.

The index encompasses three domains: education, health and environment, and social and economic resources. Higher scores are linked to better childhood health. Of the three domains, the education and social and economic resources scores were most strongly related to ADHD symptoms.

The analysis showed the Child Opportunity Index scores at birth were a strong predictor for ADHD symptoms in adolescence in the autistic children but not in the other groups. Calub noted that the finding was unexpected.

“These results are quite concerning,” Calub said. “Those with both autism and ADHD are already more likely to have additional challenges — behaviorally, cognitively, emotionally and socially. Being born in a low-income neighborhood puts them at an even greater disadvantage. This just adds to the evidence that more resources are needed for underserved areas and specifically for those who have conditions like autism.”

The need for a larger, more diverse sample

Calub pointed out that more research is needed to determine if the results would apply to a larger group.

“It will be important for future studies to be larger and more diverse. That should help us learn whether neighborhood conditions might also influence ADHD symptoms in other groups such as youth without autism, or in Black, Asian and Native American individuals, who were under-represented in our sample,” Calub added.

These findings also offer clues for how to target preventive strategies to reduce the risk of increased ADHD symptoms, noted Schweitzer, who was also a co-author on the study.

“ADHD is highly prevalent in the general population and is common in autistic youth. If we can find ways to increase resources in these neighborhoods, we have the potential to improve academic, social, mental and physical health outcomes, particularly for autistic youth, and also decrease long-term economic costs,” Schweitzer explained.

Calub and Schweizer believe the study’s findings should encourage policymakers to provide more resources for underserved communities. In addition, they hope including the Child Opportunity Index and other neighborhood metrics could provide new insights into future studies to inform policy.

Reference:

Catrina A. Calub, Irva Hertz-Picciotto, Deborah Bennett, Julie B. Schweitzer, Examining the association of neighborhood conditions on attention-deficit/hyperactivity disorder symptoms in autistic youth using the child opportunity index 2.0, JCPP Advances, https://doi.org/10.1002/jcv2.12267.

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