Patients with persistently high BP within 24 hours of ischemic stroke onset at highest risk of adverse outcomes: Study

China: A recent article published in the BMJ journal Heart has reported twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.

The researchers found that patients with persistently high blood pressure (BP) at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while they found favorable outcomes in those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg).

The management of BP in acute ischaemic stroke remains a subject of controversy. Ruirui Wang, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China, and colleagues aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes.

For this purpose, the researchers examined a cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals. Using latent mixture modeling, they identified five systolic BP trajectories: trajectory category 1 (150–130 mm Hg), trajectory category 2 (155–145 mm Hg), trajectory category 3 (170–160 mm Hg), trajectory category 4 (180–140 mm Hg), and trajectory category 5 (190–170 mm Hg).

The study’s primary outcome was a composite outcome of death and major disability at three months poststroke.

The study led to the following findings:

  • Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up.
  • Compared with the patients in trajectory category 5, adjusted ORs for the primary outcome were 0.79, 0.70, 0.64, and 0.47 among patients in trajectory category 4, trajectory category 3, trajectory category 2, and trajectory category 1, respectively.
  • Similar trends were observed for vascular events, death, and the composite outcome of death and vascular events.

In conclusion, the researchers identified distinctive BP trajectories within 24 hours post-stroke onset.

At the 3-month follow-up, patients in the highest trajectory category 5 (190–170 mm Hg) showed the highest risk of adverse outcomes (vascular events, death, and major disability), while those in the lowest category (150–130 mm Hg) exhibited the lowest risk. Comparatively, adjusted odds ratios reduced from 0.79 to 0.47, respectively.

Reference:

Wang R, Liu Y, Zhang Q, Zhang J, Peng H, Shi M, Peng Y, Xu T, Wang A, Xu T, Chen J, Zhang Y, He J. Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke. Heart. 2024 Apr 3:heartjnl-2023-323821. doi: 10.1136/heartjnl-2023-323821. Epub ahead of print. PMID: 38569853.

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Remdesivir does not increase the risk of cardiac events in COVID-19 patients, suggests study

A recent comprehensive post-hoc safety analysis found that the antiviral drug remdesivir assure cardiac safety profile. When administered to the hospitalized patients with COVID-19, it does not elevate the risk of cardiac adverse events (AEs). These finding were published in the Clinical Infectious Diseases highlight the ongoing debate about the safety of remdesivir in the COVID-19 treatment.

The analysis focused on the cardiac health of patients and was derived from the multicenter, randomized, open-label, controlled DisCoVeRy trial that compared the effects of remdesivir with standard of care (SoC) against SoC alone in hospitalized COVID-19 patients. The study scrutinized the occurrence of any first adverse event from the time of randomization up to 29 days post-treatment in a modified intention-to-treat (mITT) population.

This trial observed cardiac adverse events in 11.2% of patients in the remdesivir group (46 out of 410) and 11.3% of patients in the control group (48 out of 423) that revealed no significant difference in cardiac risk between the two groups. This similarity held true across the various analyses that included both serious and non-serious cardiac events with arrhythmic events being the most common but generally leading to favorable outcomes.

These findings are crucial after considering the outcomes of the previous studies and analyses that hinted a potential association between remdesivir treatment and cardiac AEs. However, the data from the DisCoVeRy trial suggest that remdesivir can be administered without much added concern for cardiac safety among the hospitalized patients with moderate to severe COVID-19. This aligns with the outcomes from other randomized controlled trials and meta-analyses that further strengthens the case for the safe use of remdesivir in the fight against COVID-19.

The patients and healthcare providers have been navigating the challenges of COVID-19 treatment options, with the safety and efficacy of treatments being paramount. Overall, the contribution of DisCoVeRy trial is significant by offering a sharp reassurance about the cardiac safety profile of remdesivir where these findings are vital for informing the treatment strategies and ensuring the safety of patients.

Reference:

Terzić, V., Miantezila Basilua, J., Billard, N., de Gastines, L., Belhadi, D., Fougerou-Leurent, C., Peiffer-Smadja, N., Mercier, N., Delmas, C., Ferrane, A., Dechanet, A., Poissy, J., Espérou, H., Ader, F., Hites, M., Andrejak, C., Greil, R., Paiva, J.-A., … Staub, T. (2024). Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial. In Clinical Infectious Diseases. Oxford University Press (OUP). https://doi.org/10.1093/cid/ciae170

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Irregular sleep and late bedtimes tied to worse grades for high school students, finds research

Irregular sleep and late bedtimes are linked to worse grades and more school-related behavioral problems among teens, suggests a study funded by the National Institutes of Health (NIH). The authors stated that interventions to promote regular sleep schedules may boost adolescents’ academic performance.

The study, conducted by Gina Marie Mathew, Ph.D., and Lauren Hale, Ph.D., of Stony Brook University and colleagues, appears in Sleep. Funding was provided by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Researchers analyzed data from nearly 800 adolescents participating in a larger study(link is external). Participants provided information on grades and school-related behavioral issues. They also wore a wrist accelerometer (a device that records the wearer’s movements) for a week so that study staff could estimate their sleep patterns.

Participants with more variable bedtimes had a greater chance of receiving a D or lower during the last grading period, compared to those with more consistent bedtimes. Adolescents who went to bed later, got up later or varied the number of hours they slept per night had fewer classes in which they received an A. Adolescents were more likely to be suspended or expelled in the last two years if they got up later, varied the number of hours they slept each night or if they varied the time they went to bed each night.

The authors theorized that delayed bedtimes could result in late school arrivals, which could affect learning and behavior. In addition, many adolescents are biologically inclined to later hours, which conflict with early school start times.

Reference:

Gina Marie Mathew et al, Actigraphic sleep dimensions and associations with academic functioning among adolescents, Sleep (2024). DOI: 10.1093/sleep/zsae062.

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Ketogenic diet may improve outcomes in patients with psychiatric illness: Study

A recent pilot study published in the Psychiatry Research journal found the ketogenic diet which is traditionally used in the treatment of obesity, type 2 diabetes and epilepsy to be effective in psychiatric care. This study by Shebani Sethi and team unveiled promising results for individuals with schizophrenia or bipolar disorder with pre-existing metabolic abnormalities. This 4-month single-arm trial included a total of 23 participants which suggests the strong potential of ketogenic diet as a supplementary treatment for serious mental illnesses.

The findings of this study were significant where all participants showed marked improvements in metabolic health by effectively eliminating the criteria for metabolic syndrome by the end of the study. For the individuals who strictly adhered to the ketogenic diet, the results showed an average weight loss of 12%, a reduction in BMI of 12%, a 13% decrease in waist circumference and a substantial 36% reduction in the visceral adipose tissue. These improvements in physical health were paralleled by marked enhancements in the metabolic biomarkers which included a 27% decrease in the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and a 25% reduction in triglyceride levels.

The study illuminated the potential psychiatric advantages of the ketogenic diet beyond the metabolic benefits. The participants diagnosed with schizophrenia experienced a significant 32% decrease in their Brief Psychiatric Rating Scale scores by indicating a reduction in the severity of their symptoms. The overall Clinical Global Impression (CGI) severity score improved by an average of 31%, with a significant 79% of participants showing at least a 1-point improvement in their CGI scores that denotes a reduction in symptom severity.

The cohort reported a 17% increase in life satisfaction and a 19% improvement in sleep quality which elucidates the possible far-reaching effects on overall well-being of the diet. This pilot trial stands as a strong witness to the potential benefits of the ketogenic diet as an adjunct treatment for the individuals with serious mental illnesses. The improvements in both metabolic health and psychiatric symptoms underline the dual impact of this diet in patients who seek alternative or supplementary treatment options. Overall, these findings pave the way for further research into the role of ketogenic diet in psychiatric care that can potentially revolutionize treatment approaches for schizophrenia, bipolar disorder and much more.

Source:

Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E., Krauss, R. M., & Saslow, L. (2024). Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. In Psychiatry Research (Vol. 335, p. 115866). Elsevier BV. https://doi.org/10.1016/j.psychres.2024.115866

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Solar-powered oxygen efficacious and cost-effective means of supplying oxygen in rural settings:Lancet

Solar-powered oxygen efficacious and cost-effective means of supplying oxygen in rural settings suggests a new study published in the Lancet.

Supplemental O2 is not always available at health facilities in low-income and middle-income countries (LMICs). Solar-powered O2 delivery can overcome gaps in O2 access, generating O2 independent of grid electricity. We hypothesized that installation of solar-powered O2 systems on the paediatrics ward of rural Ugandan hospitals would lead to a reduction in mortality among hypoxaemic children. In this pragmatic, country-wide, stepped-wedge, cluster randomised controlled trial, solar-powered O2 systems (ie, photovoltaic cells, battery bank, and O2 concentrator) were sequentially installed at 20 rural health facilities in Uganda. Sites were selected for inclusion based on the following criteria: District Hospital or Health Centre IV with paediatric inpatient services; supplemental O2 on the paediatric ward was not available or was unreliable; and adequate space to install solar panels, a battery bank, and electrical wiring. Allocation concealment was achieved for sites up to 2 weeks before installation, but the study was not masked overall.

Children younger than 5 years admitted to hospital with hypoxaemia and respiratory signs were included. The primary outcome was mortality within 48 h of detection of hypoxaemia. The statistical analysis used a linear mixed effects logistic regression model accounting for cluster as random effect and calendar time as fixed effect. Findings: Between June 28, 2019, and Nov 30, 2021, 2409 children were enrolled across 20 hospitals and, after exclusions, 2405 children were analysed. 964 children were enrolled before site randomisation and 1441 children were enrolled after site randomisation (intention to treat). There were 104 deaths, 91 of which occurred within 48 h of detection of hypoxaemia. The 48 h mortality was 49 (5·1%) of 964 children before randomisation and 42 (2·9%) of 1440 (one individual did not have vital status documented at 48 h) after randomisation (adjusted odds ratio 0·50, 95% CI 0·27-0·91, p=0·023). Results were sensitive to alternative parameterisations of the secular trend.

There was a relative risk reduction of 48·7% (95% CI 8·5-71·5), and a number needed to treat with solar-powered O2 of 45 (95% CI 28-230) to save one life. Use of O2 increased from 484 (50·2%) of 964 children before randomisation to 1424 (98·8%) of 1441 children after randomisation (p<0·0001). Adverse events were similar before and after randomisation and were not considered to be related to the intervention. The estimated cost-effectiveness was US$25 (6-505) per disability-adjusted life-year saved. This stepped-wedge, cluster randomised controlled trial shows the mortality benefit of improving O2 access with solar-powered O2. This study could serve as a model for scale-up of solar-powered O2 as one solution to O2 insecurity in LMICs.

Reference:

Conradi N, Opoka RO, Mian Q, Conroy AL, Hermann LL, Charles O, Amone J, Nabwire J, Lee BE, Saleh A, Mandhane P, Namasopo S, Hawkes MT. Solar-powered O2 delivery for the treatment of children with hypoxaemia in Uganda: a stepped-wedge, cluster randomised controlled trial. Lancet. 2024 Feb 24;403(10428):756-765. doi: 10.1016/S0140-6736(23)02502-3. Epub 2024 Feb 14. PMID: 38367643.

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FDA clears AI tool to detect heart failure with low ejection fraction

The US Food and Drug Administration (FDA) has cleared first AI tool to detect heart failure with low ejection fraction.

Eko Low Ejection Fraction Tool (ELEFT) is an algorithm intended to aid treating physicians in identifying individuals 18 years and older with left ventricular ejection fraction (LVEF) less than or equal to 40%.

For the first time, U.S. healthcare providers can now detect Low EF, a key heart failure indicator, in 15 seconds using an Eko stethoscope during a routine physical examination. This leap in early detection marks both a significant medical innovation and a new era in the detection of cardiovascular disease.

In the U.S., more than 6 million people battle heart failure, with half of them experiencing heart failure with reduced ejection fraction (HFrEF)-a condition marked by the heart’s inability to pump blood effectively. Traditional heart failure detection tools, such as echocardiography, are often unavailable in primary care settings as they are costly, require specialized training, and add significant time. As a result, many heart failure cases go undiagnosed until symptoms force a specialist or emergency hospital visit, leading to worse patient outcomes and exacerbated healthcare costs. Eko’s Low EF AI disrupts this status quo by embedding rapid and accessible low ejection fraction detection into a stethoscope exam on the front lines of care.

“The ability to identify a hidden, potentially life-threatening heart condition using a tool that primary care and subspecialist clinicians are familiar with – the stethoscope – can help us prevent hospitalizations and adverse events,” said Dr. Paul Friedman, Chair of the Department of Cardiovascular Medicine at Mayo Clinic in Rochester. “Importantly, since a stethoscope is small and portable, this technology can be used in urban and remote locations, and hopefully help address care in underserved areas.”

The Low EF AI will be added to Eko’s SENSORA Cardiac Early Detection Platform, the latest advancement to the platform which already features FDA-cleared algorithms to identify AFib and structural heart murmurs, often an indicator of valvular heart disease. When Low EF is detected in a primary care exam with SENSORA, access to life-extending treatment can be expedited with a referral to the cardiology department for thorough diagnostic testing and treatment evaluation.

“The stethoscope, the most recognizable symbol of healthcare, touches the lives of an estimated one billion people around the globe every year,” said Connor Landgraf, co-founder & CEO of Eko Health. “With Eko’s Low EF AI, we’ve transformed the icon of medicine into an AI-powered heart failure early detection tool that can help improve access to care for millions of patients, at a fraction of the time and cost of echocardiography. It’s been a privilege to work alongside Mayo Clinic in this groundbreaking endeavor.”

Clinical Development & Validation Highlights:

  • Robust AI Training & Validation: Eko’s Low EF AI was trained on a proprietary dataset of over 100,000 ECGs and echocardiogram pairs from unique patients, and was clinically validated in a multi-site, prospective clinical study of 3,456 patients, achieving an AUROC of 0.835 for detection of LVEF <40%, 74.7% sensitivity and 77.5% specificity, demonstrating a strong ability to differentiate between low and normal EF.
  • Imperial College London Independent Validation: An independent validation of the Low EF AI by the Imperial College London, published in Lancet Digital Health, reported an AUROC of 0.85 for detection of LVEF below 40%, 84.8% sensitivity, and 69.5% specificity when deployed on over 1,050 patients across multiple real-world settings. This validation prompted the UK NHS and Imperial College London to extend Eko’s deployment to over 100 clinics in London and Wales.
  • Demonstrated Impact in Pregnant Women: A clinical study led by Mayo Clinic involving nearly 1,200 pregnant women in Nigeria highlighted the AI’s effectiveness, identifying twice as many cases of pregnancy-related cardiomyopathy than standard care, with an impressive AUROC of 0.98, 100.0% sensitivity, and 79.4% specificity, underscoring its significant potential to assist in the detection and appropriate management of cardiomyopathy in pregnant women, reducing associated disease burden and risk of death.

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Patients taking semaglutide may have higher rate of “altered skin sensations” and alopecia, finds review

USA: A review of 22 articles published in the Journal of the American Academy of Dermatology found that patients taking oral semaglutide had a higher rate of “altered skin sensations” and alopecia when compared with those getting a placebo.

“Variations in administration routes and dosage could impact the types and severity of skin findings, highlighting the need for additional research,” Megan M. Tran, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA, and colleagues wrote in their study.

The MedWatch program of the US Food and Drug Administration (FDA) has not received reports of semaglutide-related safety events, and few studies have characterized skin findings associated with subcutaneous or oral semaglutide, a glucagon-like peptide 1 agonist used for obesity and type 2 diabetes treatment.

The scoping review included 22 articles (15 clinical trials, six case reports, and one retrospective cohort study), published through January 2024, of patients receiving either semaglutide or a placebo or comparator, including reports of semaglutide-associated adverse dermatologic events in 255 participants.

Based on the review, the researchers reported the following findings:

  • Patients who received weekly 50 mg oral semaglutide reported a higher incidence of altered skin sensations, such as dysesthesia (1.8% versus 0%), hyperesthesia (1.2% versus 0%), skin pain (2.4% versus 0%), paresthesia (2.7% versus 0%), and sensitive skin (2.7% versus 0%), than those receiving placebo or comparator.
  • Reports of alopecia (6.9% versus 0.3%) were higher in patients who received 50 mg oral semaglutide weekly than in those on placebo, however, only 0.2% of patients on 2.4 mg of subcutaneous semaglutide reported alopecia versus 0.5% of those on placebo.
  • Unspecified dermatologic reactions (4.1% vs 1.5%) were reported in more patients on subcutaneous semaglutide than those on a placebo or comparator.
  • Several case reports described isolated cases of severe skin-related adverse effects, such as bullous pemphigoid, eosinophilic fasciitis, and leukocytoclastic vasculitis.
  • Injection site reactions (3.5% vs 6.7%) were less common in patients on subcutaneous semaglutide than those on a placebo or comparator.

The limitation of the study is that it could not adjust for confounding factors and could not establish a direct causal association between semaglutide and the adverse reactions reported.

In conclusion, the review of 22 articles revealed that patients taking oral semaglutide had a higher rate of alopecia and “altered skin sensations” when compared with those getting a placebo.

Variations in dosage and administration routes could influence the severity and types of skin findings, underscoring the need for additional research.

Reference:

Tran, M. M., Mirza, F. N., Lee, A. C., Goldbach, H., Libby, T. J., & Wisco, O. J. (2024). Dermatologic findings associated with semaglutide use: A scoping review. Journal of the American Academy of Dermatology. https://doi.org/10.1016/j.jaad.2024.03.021

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Early coronary disease, impaired heart function found in asymptomatic people with HIV: Study

A new study found increased coronary vessel wall thickness that was significantly associated with impaired diastolic function in asymptomatic, middle-aged individuals living with HIV. The study was published  in Radiology: Cardiothoracic Imaging, a journal of the Radiological Society of North America (RSNA).

According to the World Health Organization, approximately 39 million people were living with HIV at the end of 2022. Since 2010, HIV-related deaths have been reduced by 51%, but HIV continues to be a major global public health issue, claiming 40.4 million lives so far.

As effective therapy drugs increase the life expectancy for people living with HIV, non-AIDS-related health concerns are increasingly common. Recent research has shown that cardiovascular disease is higher in persons living with HIV compared with individuals without HIV, with an estimated 4-fold higher rate of sudden cardiac death compared with the general population.

Researchers at the National Institutes of Health (NIH) set out to assess early coronary atherosclerosis burden, and its relation to how the heart is functioning, in people living with HIV who were asymptomatic and had low cardiovascular disease risk. For the study, the researchers recruited 74 adults (mean age of 49 years) living with HIV without known cardiovascular disease and 25 matched healthy controls (mean age of 46 years). Controls were negative for HIV and were required to be healthy with no known significant medical conditions, including coronary disease. All underwent MRI to measure coronary vessel wall thickness and an echocardiogram to assess left ventricular function.

“Prior studies have shown cardiovascular disease in persons living with HIV, however not at such an early stage,” said senior author Ahmed M. Gharib, M.D., senior clinical investigator, and director of the Biomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in Bethesda, Maryland.

The HIV and control groups were matched by corresponding age, sex and race. A detailed medical history, physical examination and laboratory tests were obtained from participants, including detailed review of any exposure to antiretroviral therapy-the combination of several antiretroviral medicines used to slow the rate at which HIV makes copies of itself (multiplies) in the body-and traditional cardiovascular disease risk factors. Each participant had lab tests that included the following: fasting lipid panel, T-cell counts and HIV viral load.

The results showed increased coronary vessel wall thickness in the HIV group, compared to controls. The increased coronary artery vessel wall thickness was independently associated with elevated left ventricular mass index and impaired diastolic function.

Coronary artery vessel wall thickness was also associated with the duration of exposure to didanosine, one of the medications used in combination with other drugs for the treatment of HIV.

“The ability to detect early coronary artery disease in persons living with HIV and potentially prevent detrimental effects on the heart muscle is important,” said lead author Khaled Z. Abd-Elmoniem, Ph.D., M.H.S., staff scientist in NIDDK’s Biomedical and Metabolic Imaging Branch. “This research shows the impact of HIV on developing subtle subclinical coronary artery disease and its effects on heart function.”

The researchers emphasized that early identification of subclinical cardiovascular disease in young HIV patients is an urgent necessity, potentially opening avenues for more effective intervention and disease management.

Reference:

Khaled Z. Abd-Elmoniem, Hadjira Ishaq, Julia Purdy, Jatin Matta, Ahmed Hamimi, Hwaida Hannoush, Colleen Hadigan , Ahmed M. Gharib, Association of Coronary Wall Thickening and Diminished Diastolic Function in Asymptomatic, Low Cardiovascular Disease–Risk Persons Living with HIV, Radiology Cardiothoracic Imaging, https://doi.org/10.1148/ryct.230102.

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Preemptive use of corticosteroids enhances success of local anesthesia among patients undergoing endodontic therapy: Study

Preemptive use of corticosteroids enhances the success of local anaesthesia among patients undergoing endodontic therapy suggests a study published in the Journal of Endodontics.

Chronic inflammation in irreversible pulpitis leads to heightened sensitivity of nociceptive receptors, resulting in persistent hyperalgesia. This poses significant challenges in achieving effective anesthesia for patients with irreversible pulpitis. Various anesthetic techniques and pharmacological approaches have been employed to enhance the success of local anesthesia. Recently, the preemptive use of anti-inflammatory agents, specifically corticosteroids, has gained attention and shown promising results in randomized controlled trials. This systemic review and meta-analysis aimed to evaluate the impact of systemically administered corticosteroids on enhancing anesthetic success in patients undergoing endodontic treatment. A comprehensive search was conducted across multiple databases including PubMed, Cochrane Library, Embase, Scopus, Dentistry & Oral Science, and ProQuest. Additionally, the references of primary studies and related systematic reviews were manually searched for additional relevant publications.

The primary outcome assessed was the success of anesthesia, and the effect measure was Risk Ratio (RR) using the random-effects inverse variance method. Statistical significance was set at p < .05. The certainty of the evidence was evaluated using the GRADE approach. Results: Twelve studies involving 917 participants were analyzed to determine the frequency of successful anesthesia. The corticosteroid group demonstrated a significantly higher number of patients achieving successful anesthesia (RR = 1.66; 95% CI, 1.34 to 2.06;p< .00001). However, heterogeneity within the pooled data analysis was observed (I2= 57%,p=0.007). Moderate certainty evidence indicates that preemptive use of systemic corticosteroids enhances the success of local anesthesia, specifically inferior alveolar nerve block (IANB), in cases of irreversible pulpitis.

Reference:

Alajlan N, Carrasco-Labra A, Karabucak B, Lee SM. Systemic Corticosteroid Uses in Endodontics- Part 2: Enhancing the Success of Local Anesthesia. J Endod. 2024 Mar 13:S0099-2399(24)00161-4. doi: 10.1016/j.joen.2024.03.002. Epub ahead of print. PMID: 38490300.

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Radiation before mastectomy cuts time delays for reconstructive surgery in breast cancer patients: JAMA

Researchers at The University of Texas MD Anderson Cancer Center showed that altering the sequence of breast cancer treatment to administer radiation before mastectomy allowed for concurrent breast reconstruction surgery, which reduced the number of operations required, minimized treatment delays and improved patient satisfaction.

The Phase II trial results, published in JAMA Network Open, evaluated 49 patients who received radiation therapy followed by mastectomy with immediate breast reconstruction. There were no complete flap losses or disease recurrences at a median of 29.7 months of follow-up.

“Our trial represents a pioneering achievement in the U.S., demonstrating the safety and effectiveness of this paradigm-shifting treatment sequence for patients with breast cancer,” said lead author Mark Schaverien, M.D., associate professor of Plastic Surgery. “This sequence not only enhances surgical outcomes but also eliminates the need for patients to defer breast reconstruction surgery, significantly enhancing their quality of life.”

Currently, when planning breast reconstruction for patients needing radiation therapy after mastectomy, the main goal is to prevent radiation from reaching the final reconstruction. This is done to reduce long-term side effects and to ensure patients are happy with the results.

Typically, women have a tissue expander placed during their mastectomy procedure, which is expanded with saline. This is followed by approximately six weeks of daily radiation therapy to the remaining chest wall and lymph node tissues. Final reconstruction is typically deferred until 6-12 months after radiation.

During the time between radiation and final reconstruction, there are negative quality-of-life effects from not having a reconstructed breast and potential negative medical effects from the tissue expander, with one in five women experiencing complications resulting in removal of the expander.

Schaverien explains that changing the order of treatment, to begin with radiation followed by mastectomy with breast reconstruction in one operation, provides immediate benefits to the patient.

The study enrolled women from participants in the SAPHIRE trial. The median age was 48 years, and 94% of patients had received neoadjuvant systemic therapy. Twenty-four patients were randomized to receive short course (40.05 Gy/15 fractions) and 25 to receive standard course (50 Gy/25 fractions) radiation therapy to the chest wall and regional lymph nodes. Patients underwent mastectomy with immediate breast reconstruction surgery, at a median of 23 days after completing radiotherapy.

The rate of surgical complications after the operation was similar to the complication rate from standard-of-care reconstructive surgery, showing a favorable comparison. Patients who underwent hypofractionated (short course) radiation therapy exhibited similar complication rates to those receiving conventional (standard course) radiation therapy. All the patients who underwent tissue-based reconstruction had successful reconstructive surgeries and none of these patients had any serious complications in follow-up.

“For many patients, this approach represents a significant breakthrough,” said co-author Benjamin Smith, M.D., professor of Radiation Oncology and Health Services Research. “It allows women to swiftly resume their lives following breast cancer treatment, feeling and looking confident, without the need for prolonged delays before undergoing reconstructive surgery.”

These findings led to the initiation of the Phase III TOPAz trial, which is currently enrolling patients. The study aims to compare the standard amount and timing of radiation treatment with a reduced radiation dose given before breast cancer removal and reconstruction surgery.

Reference:

Schaverien MV, Singh P, Smith BD, et al. Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(4):e245217. doi:10.1001/jamanetworkopen.2024.5217.

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