Archive for month: December, 2024

A new study published in the Journal of American Medical Association showed that young males who use or have previously used anabolic-androgenic steroids (AASs) are more likely to have a lower myocardial flow reserve when compared to those who have never used the medicines.

Although the exact mechanism of development is unknown, long-term use of anabolic androgenic steroids is linked to a significant risk of left ventricular hypertrophy, heart failure with impaired systolic function, and early abrupt death. In the men who use AAS, early and persistently decreased myocardial microcirculation may be clinically significant, a possible underlying cause of frequent and early heart illness, and a future target for treatments.

This study used cardiac rubidium 82 (82Rb) positron emission tomography/computed tomography (PET/CT) to measure myocardial flow reserve (MFR) in males who now and previously used AAS in comparison to controls who had never used AAS. This was done to evaluate coronary microcirculation.

Men who participated in recreational strength training and did not have a history of cardiovascular disease were included in this cross-sectional study based on their history of using AAS. From November 24, 2021, until August 16, 2023, the study was carried out. The MFR between the research groups was the main result of this investigation, while the coronary calcium score was the secondary result. By definition, a threshold of MFR less than 2 was used to identify impaired myocardial microcirculation, while a cutoff of MFR less than 2.5 was used to identify sub-clinically impaired microcirculation.

There were 90 men in all and 35.1 years was the mean (SD) age. A 1.5-year geometric mean was the amount of time that had passed from AAS discontinuation. Before enrolling, 18 males (58.1%) who had previously used AAS stopped using it more than a year earlier. Impaired MFR was seen in individuals with current and past usage, but no impairment was detected among the controls. When compared to the controls, men who now or previously used AAS had a greater sub-clinically impaired MFR.

Every doubling of the total weekly duration of AAS usage (log2) was independently linked to a factor 2 increase in the chance of impaired MFR less than 2.5 in a multivariable logistic regression model among men who had previously used AAS. Overall, both present and previous AAS users in this cross-sectional research showed reduced MFR which indicated a link between AAS use and lower MFR.

Reference:

Bulut, Y., Rasmussen, J. J., Brandt-Jacobsen, N., Frystyk, J., Thevis, M., Schou, M., Gustafsson, F., Hasbak, P., & Kistorp, C. (2024). Coronary Microvascular Dysfunction Years After Cessation of Anabolic Androgenic Steroid Use. In JAMA Network Open (Vol. 7, Issue 12, p. e2451013). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.51013

A new method of scanning lungs is able to show the effects of treatment on lung function in real time and enable experts to see the functioning of transplanted lungs.

This could enable medics to identify sooner any decline in lung function.

The scan method has enabled the team, led by researchers at Newcastle University, UK, to see how air moves in and out of the lungs as people take a breath in patients with asthma, chronic obstructive pulmonary disease (COPD), and patients who have received a lung transplant.

Publishing two complementary papers in Radiology and JHLT Open, the team explain how they use a special gas, called perfluoropropane, that can be seen on an MRI scanner. The gas can be safely breathed in and out by patients, and then scans taken to look at where in the lungs the gas has reached.

The project lead, Professor Pete Thelwall is Professor of Magnetic Resonance Physics and Director of the Centre for In Vivo Imaging at Newcastle University. He said; “Our scans show where there is patchy ventilation in patients with lung disease, and show us which parts of the lung improve with treatment. For example, when we scan a patient as they use their asthma medication, we can see how much of their lungs and which parts of their lung are better able to move air in and out with each breath.”

Using the new scanning method, the team are able to reveal the parts of the lung that air doesn’t reach properly during breathing. By measuring how much of the lung is well-ventilated and how much is poorly ventilated, experts can make an assessment of the effects of a patient’s respiratory disease, and they can locate and visualise the lung regions with ventilation defects.

Demonstrating that the scans work in patients with asthma or COPD, the team comprising experts from across Universities and NHS Trusts in Newcastle and Sheffield publish the first paper in Radiology.

The new scanning technique allows the team to quantify the degree of improvement in ventilation when patients have a treatment, in this case a widely used inhaler, the bronchodilator, salbutamol. This shows that the imaging methods could be valuable in clinical trials of new treatments of lung disease.

Use in lung transplants

A further study, published in JHLT Open, examined patients who had previously received a lung transplant for very severe lung disease at the Newcastle upon Tyne Hospitals NHS Foundation Trust. It demonstrates how the team further developed the imaging method to provide lung function measurements which could be used to better support lung transplant recipients in the future. The sensitivity of the measurement means medics can spot early changes in lung function allowing them to identify lung problems earlier and so provide better care for patients.

In research studies, the team scanned transplant recipients’ lungs over multiple breaths in and out, collecting MRI pictures that show how the air containing the gas reached different areas of the lung. The team scanned those who either had normal lung function or who were experiencing chronic rejection after lung transplant, which is a common issue in lung transplant recipients as their immune system attacks the donor lungs. In those with chronic rejection, the scans showed poorer movement of air to the edges of the lungs, most likely due to damage in the very small breathing tubes (airways) in the lung, a feature typical of chronic rejection also known as chronic lung allograft dysfunction.

Professor Andrew Fisher, Professor of Respiratory Transplant Medicine at Newcastle Hospitals NHS Foundation Trust and Newcastle University, UK, co-author of the study said; “We hope this new type of scan might allow us to see changes in the transplant lungs earlier and before signs of damage are present in the usual blowing tests. This would allow any treatment to be started earlier and help protect the transplanted lungs from further damage.”

The team say there is potential for this scan method to be used in the clinical management of lung transplant recipients and other lung diseases in the future, bringing a sensitive measurement that may spot early changes in lung function that enable better management of these conditions.

This work on lung imaging has been funded by the Medical Research Council and by The Rosetrees Trust.

References: Assessing Lung Ventilation and Bronchodilator Response in Asthma and Chronic Obstructive Pulmonary Disease with Fluorine 19 MRI. Pippard BJ, Neal MA, Holland CW, Maunder AM, Forrest I, Lawson RA, Fisher HF, Matthews JNS, Wild JM, Simpson AJ, Thelwall, PE. Radiology. Doi: https://doi.org/10.1148/radiol.240949 (n.b. live date 24th Dec)

A recent study published in the
journal JAMA Ophthalmology found that substituting micro drops with standard
drops was non-inferior as it reduced the systemic effects in preterm infants
who have retinopathy of prematurity.

Also Read: New Eye Drop Therapy For Dry Age Related Macular Degeneration: Study Finds

Also Read: Perfluorohexyloctane Eyedrops safe for contact lens wearers and may reduce contact lens dropout: Study

An estimated 13.8 million people in the U.S. will have Alzheimer’s disease (AD) by 2050, two thirds of whom are projected to be women. The brain circuitry underlying memory is widely known to differ based on biological sex, but sex-based drivers of aging and AD are still unclear. A new study by investigators from Mass General Brigham analyzed data from participants who have been followed for over 50 years, starting before their births. Researchers found that maternal immune activity during a critical period of sex-dependent brain development in pregnancy affected the offspring’s long-term memory circuitry and function in childhood and midlife, with different patterns for males and females. Findings are published in Molecular Psychiatry.

“Brain aging is also about brain development, and understanding sex differences in brain development is critical to understanding sex differences in the aging brain,” said corresponding author Jill M. Goldstein, PhD, MPH, founder and executive director of the Innovation Center on Sex Differences in Medicine of Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, and Professor of Psychiatry and Medicine at Harvard Medical School. “This paper is a first step toward looking at the fetal origins of Alzheimer’s disease, which, like many chronic diseases, develops across the lifespan and is influenced by early development in a way we might not ordinarily consider.”

This study was based on findings from a cohort established over 60 years ago, which includes the adult offspring of nearly 18,000 pregnancies between 1959 and 1966, followed as part of the New England Family Study (NEFS). The present investigation comprised 204 individuals born during the study who were or were not exposed to an adverse in utero immune environment (i.e., elevated levels of immune markers, such as cytokines IL-6 and TNF-a) and followed into midlife 50 years later. The team used functional brain imaging to examine the impact of this early exposure on brain regions in the memory circuitry that are dense in these cytokine receptors and sex hormone receptors and exhibit sex differences in development and functioning beginning in fetal development.

The researchers found that elevated levels of IL-6 and TNF-a in mothers during pregnancy were linked with sex differences in adverse brain activity in memory circuitry in the offspring later in life, particularly in postmenopausal women. These women also expressed higher markers of a proinflammatory state in midlife. Further, researchers saw evidence of the impact of these immune markers even earlier, in children’s cognitive performance at age seven, underscoring the link between exposures during pregnancy and brain health later in life. Their findings suggest that elevated maternal prenatal immune activity may contribute to the development of heightened immune and stress sensitivity in the offspring, which, the researchers hypothesized, may predispose them to memory disorders, like AD, later in life, in sex-dependent ways.

As participants age, the researchers are continuing to follow them to examine amyloid levels and other measures of AD-related pathology to further explore the association between prenatal immunity and AD. Ongoing goals include understanding the mechanisms by which maternal immune activity influences fetal brain development, identifying biomarkers for future memory dysfunction in early midlife, and understanding how other periods of development, such as puberty, influence the aging brain.

“While prenatal immune activity may affect brain development in the offspring, that does not mean pregnancy is deterministic,” Goldstein said. “Of course, subsequent environmental exposures are key, just as in utero environment is important. Fortunately, the brain is exceptionally adaptable, and we want to understand the cognitive, behavioral, and sex-dependent factors associated with both risk and resilience in order to intervene early and maintain intact memory function as we age.”

Reference:

Goldstein, J.M., Konishi, K., Aroner, S. et al. Prenatal immune origins of brain aging differ by sex. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02798-w

A new study published in the journal of Gastrointestinal Endoscopy showed that for some individuals with chronic pancreatitis (CP), pancreatic endotherapy (PET) can improve quality of life and reduce discomfort. The primary symptom of chronic pancreatitis, pain, is still challenging to successfully manage and can considerably lower a patient’s quality of life. The mechanism of pain is probably influenced by a number of factors, such as inflammation, ductal hypertension, or neuropathic pain resulting from different levels of nervous system sensitization.

The patients with CP-related structural problems, such as pancreatic duct (PD) stones, strictures, stones, or pancreatic fluid collections, such pseudocysts, may benefit from pancreatic endotherapy. Pancreatic duct stones, strictures, and pancreatic fluid collections are among the structural problems associated with chronic pancreatitis that can be managed with pancreatic endotherapy. However, the majority of research on endotherapy has been on technical success outcomes such stricture resolution or stone removal. Thus, this review is to describe in detail how PET affects the quality of life of CP patients.

A validated CP-specific quality of life instrument (PANQOLI) was used in this single-center prospective trial to evaluate quality of life prior to the start of endotherapy. At 1, 3, 6, and 12 months of follow-up, quality of life, pain levels, and opiate use were also assessed. Celiac plexus block (EUS-CPB), EUS-guided pseudocyst drainage, PD stone lithotripsy, and therapeutic PD stent insertion were among the PET modalities. At each follow-up point, quality of life changes before and after PET were compared using a repeated measures mixed effects model.

In all, 120 CP subjects were involved in this investigation. The most common PET modalities were EUS-CPB (32.5%), PD stone lithotripsy (16.7%), and therapeutic PD stenting (49.2%). At 1, 3, 6, and 12 months after completing the PET, there were notable improvements in quality of life scores, with the biggest improvement occurring at 6 months.

At the 1- and 6-month follow-ups, there were notable reductions in pain levels; but, at the 12-month follow-up, there were none. Opiate use decreased at every follow-up point. Despite pancreatic endotherapy has been linked to improvements in quality of life for up to a year after treatment, pain relief was only observed 6 months after treatment which indicates the difficulty of managing pain in this challenging patient population. 

Source:

Han, S., Rueb, N., Nikahd, M., Pessorrusso, F., Wani, S., Edmundowicz, S. A., Duloy, A., Hammad, H. T., & Shah, R. J. (2024). The Impact of Pancreatic Endotherapy on Quality of Life in Chronic Pancreatitis. In Gastrointestinal Endoscopy. Elsevier BV. https://doi.org/10.1016/j.gie.2024.12.002