Diabetes Increases Risk of Infection After Ankle Replacement Surgery, Study Finds

Patients with diabetes undergoing total ankle arthroplasty (TAA) face a significantly higher risk of postoperative infections compared to those without the condition, according to a new study. The study results were published in the journal Foot Ankle International. 

The research, drawing on data from over 8,000 patients, highlights the increased challenges diabetic patients may encounter following ankle replacement surgery. Postoperative infections, aseptic loosening, and other perioperative medical complications present significant challenges following total ankle arthroplasty (TAA). Total ankle arthroplasty is performed to relieve pain and restore function in patients with ankle arthritis. While the procedure is generally effective, it comes with risks such as infections and the loosening of the artificial joint over time. Previous studies have indicated that diabetes could increase the likelihood of surgical complications, but the extent of its impact on ankle surgeries was not fully understood until now.
The study utilized a large insurance database to identify patients who underwent TAA between 2010 and 2021. Researchers focused on comparing the postoperative outcomes between patients diagnosed with diabetes and those without. Specifically, they examined the incidence of all-cause revision, periprosthetic joint infection (PJI), septic revision (where the joint must be surgically cleaned or replaced due to infection), and aseptic revision (surgery not related to infection).
Results revealed that within five years of undergoing TAA, 7.3% of diabetic patients were diagnosed with a periprosthetic joint infection, compared to just 3.9% of non-diabetic patients. This marked a 95% increased risk of infection for those with diabetes. Furthermore, the incidence of septic revision was 1.4% in diabetic patients, significantly higher than the 0.4% observed in non-diabetics, translating to a 363% increased risk. Interestingly, the study found no significant difference in the overall rate of joint revisions between the two groups, suggesting that while diabetes increases the risk of specific serious complications like infections, it does not affect the broader likelihood of needing a joint revision for other reasons.
These findings underscore the importance of targeted perioperative management for diabetic patients undergoing ankle replacement surgery. Tailored strategies could help mitigate the increased risk of infection and improve outcomes for this vulnerable group.This comprehensive analysis not only confirms diabetes as a significant risk factor for postoperative complications in ankle replacement but also calls for further research to develop effective preventive measures. As the diabetic population continues to grow, understanding and addressing these risks becomes increasingly crucial in orthopedic surgery.

Further reading: Helbing J, Farley B, Gu A, et al. Diabetes Mellitus and Total Ankle Arthroplasty Complications. Foot Ankle Int. Published online February 8, 2024. doi:10.1177/10711007241226929

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SGLT2 Inhibitors vs. DPP4 Inhibitors: Study reveals new benefits of SGLT2i for prevention of hypertension

Japan: A recent study published in Hypertension Research using nationwide real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in reducing hypertension development in patients with diabetes.

In the realm of hypertension management, the emergence of novel pharmacotherapies has sparked interest in their comparative effectiveness. Among these, sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have gained prominence for their potential benefits beyond glycemic control.

The analysis used a nationwide large-scale health check-up and insurance claims dataset, including approximately 20,000 patients with diabetes, and compared the subsequent risk of hypertension development between SGLT2i and DPP4i users after propensity score matching. The administration of SGLT2 inhibitors was associated with a decreased risk of developing hypertension compared with DPP4i administration

“To our knowledge, this is the first study to demonstrate the possible advantage of SGLT2 inhibitors in incident hypertension using a large-scale epidemiological database,” the researchers wrote.

SGLT2 inhibitors act by inhibiting renal glucose reabsorption, leading to glycosuria and natriuresis. Beyond glycemic control, they exhibit favorable effects on cardiovascular and renal outcomes. Conversely, DPP4 inhibitors enhance insulin secretion while reducing glucagon levels, primarily targeting glycemic control by inhibiting the degradation of incretin hormones.

Although several randomized clinical trials (RCTs) have reported the potential benefit of SGLT2 inhibitors in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. Therefore, Hidehiro Kaneko, The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan, and colleagues analyzed individuals with diabetes who were newly prescribed SGLT2i or DPP4i in a large-scale epidemiological database.

The primary outcome was the incidence of hypertension. To compare the subsequent development of hypertension between the SGLT2i and DPP4i groups, a propensity score matching algorithm was employed. After propensity score matching, 5708 well-balanced pairs of SGLT2i and DPP4i users were identified.

The findings of the study were as follows:

  • SGLT2i administration was associated with a reduced risk of hypertension (HR 0.91).
  • The advantage of SGLT2i use over DPP4i use for incident hypertension was generally consistent in several sensitivity analyses, and subgroup analyses revealed that SGLT2i use was significantly associated with a lower risk of hypertension in men, patients with baseline HbA1c of <7.5%, and baseline systolic blood pressure ≥127 mmHg.

In conclusion, in real-world practice, there was a reduced risk of developing hypertension in individuals with diabetes who were newly prescribed SGLT2i compared to those who were newly prescribed DPP4i.

The study findings shed light on the new benefits of SGLT2 inhibitors as a hypertensive preventive medication.

Reference:

Suzuki, Y., Kaneko, H., Okada, A., Komuro, J., Fujiu, K., Takeda, N., Morita, H., Ako, J., Nishiyama, A., Yano, Y., Ieda, M., Node, K., Yasunaga, H., & Komuro, I. (2024). Comparison of incident hypertension between SGLT2 inhibitors vs. DPP4 inhibitors. Hypertension Research, 1-8. https://doi.org/10.1038/s41440-024-01649-z

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Low Insulin Sensitivity Linked to Albuminuria Development in Diabetes Patients: Study

A recent study uncovered a significant link between reduced insulin sensitivity and the development of albuminuria, a key marker of kidney damage, in individuals with diabetes. This finding were published in the journal of Diabetes, Obesity and Metabolism.

This study was conducted among Southwestern Indigenous American adults to investigate the association between insulin action and secretion measured before the onset of diabetes and the subsequent development of albuminuria after diabetes onset. The team led by Meeah Willig meticulously assessed baseline body composition, insulin sensitivity at different levels of insulin stimulation and insulin secretion in a total of 170 participants who eventually developed diabetes.

Over a median follow-up period of 13.6 years, approximately 48% of the participants developed albuminuria which indicates renal impairment. The individuals who developed albuminuria expressed similar demographic characteristics, such as age, sex and body fat percentage when compared to the individuals who did not. However, they displayed significantly lower insulin sensitivity, particularly at submaximal and maximal insulin stimulation levels.

Further analysis revealed a compelling association between lower insulin sensitivity and an elevated risk of albuminuria. Also, the participants with lower insulin sensitivity levels demonstrated a 51% higher risk of developing albuminuria when compared to the individuals with higher sensitivity levels. This suggests that impaired insulin signaling may play a crucial role in the pathogenesis of proteinuria which is a hallmark of kidney damage in diabetes.

The study underlines the crucial role of insulin sensitivity in renal health among individuals with diabetes while insulin secretion did not show a significant association with the risk of albuminuria. These findings have significant implications for the management of diabetes and highlight the importance of addressing insulin resistance to prevent renal complications.

Source:

Willig, M. R., Stinson, E. J., Looker, H. C., Piaggi, P., Mitchell, C. M., Hanson, R. L., Nelson, R. G., Krakoff, J., & Chang, D. C. (2024). Insulin resistance before type 2 diabetes onset is associated with increased risk of albuminuria after diabetes onset: A prospective cohort study. In Diabetes, Obesity and Metabolism. Wiley. https://doi.org/10.1111/dom.15505

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Increased viral load and weaker immune response tied to severe COVID-19 infection among elderly, reveals study

As the COVID-19 pandemic continues to affect people of all ages, a new study has delved into the reasons why older individuals face a higher risk of severe illness from the virus. The study found that the most severe impact was seen in the oldest adults, who exhibited higher levels of pro-inflammatory genes and proteins during severe disease, indicating that the body’s response to the virus becomes increasingly dysregulated with age. The study results were published in the journal Science Translational Medicine. 

The research, conducted on a cohort of 1,031 vaccine-naïve patients hospitalized for COVID-19, aimed to unravel the mysteries behind the relationship between age and disease severity. Led by a team of researchers, the study focused on analyzing the immune response of individuals across a wide age range, from 18 to 96 years old. Using advanced techniques such as mass cytometry, serum protein profiling, antibody assays, and transcriptomics, the scientists explored how aging influences the body’s ability to combat the virus. Their findings revealed several key insights into the impact of age on COVID-19 outcomes. Firstly, older patients exhibited higher levels of the virus upon hospital admission and experienced delayed clearance of the virus from their bodies. This suggests that aging may impair the body’s ability to effectively eliminate the virus, leading to prolonged illness and increased risk of complications.
Furthermore, the study uncovered age-related changes in the immune system, with older individuals showing alterations in both innate and adaptive immune responses. Specifically, there was an upregulation of innate immune signaling pathways and a downregulation of adaptive immune signaling pathways in older patients. This imbalance in immune function could contribute to the severity of COVID-19 in older adults. One notable finding was the decrease in naïve T and B cells—the immune cells responsible for recognizing and attacking new pathogens—in older individuals. Additionally, older patients had higher levels of monocytes, which are involved in inflammatory responses, further highlighting the dysregulation of the immune system with age. Importantly, the study also revealed that older adults experienced sustained activation of pro-inflammatory genes and elevated levels of serum chemokines, which are proteins involved in guiding immune cells to infection sites. This persistent inflammatory response may contribute to the development of severe COVID-19 symptoms in older patients.
The most concerning aspect of the research was the observation that the oldest adults exhibited the highest levels of pro-inflammatory genes and proteins during severe disease, indicating a heightened risk of complications with age. Overall, the study provides valuable insights into the biological mechanisms underlying the increased susceptibility of older individuals to severe COVID-19. By understanding these mechanisms, researchers hope to develop targeted treatments that could help improve outcomes for older patients battling the virus.

Further reading: Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology. Doi: 10.1126/scitranslmed.adj51

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Immune Checkpoint Inhibitors Not Linked to Increased Pregnancy Risks: JAMA

Researchers have found in a new study that exposure to immune checkpoint inhibitors (ICIs) during pregnancy did not demonstrate an increased risk of specific adverse outcomes overall among mother or fetus.

The cohort study delved into the risks associated with immune checkpoint inhibitor (ICI) exposure during pregnancy, addressing concerns about maternal and fetal health outcomes. The findings from the study shed light on the safety of immune checkpoint inhibitors (ICIs) during pregnancy, addressing concerns about maternal and fetal health outcomes. With the widespread use of ICIs in cancer treatment, understanding their impact on pregnancy-related adverse events is crucial for informed clinical decision-making and patient care.

The study aimed to assess the risk of adverse outcomes associated with ICI exposure compared to other anticancer agents, providing valuable insights into the safety profile of these medications during pregnancy. This study was published in JAMA Network Open by Paul G. and colleagues. Existing data on the risk of adverse pregnancy outcomes associated with ICI exposure are limited, necessitating comprehensive research in this area.

The cohort study analyzed data extracted from the World Health Organization international pharmacovigilance database VigiBase, encompassing reports of pregnancy-related conditions and the use of anticancer agents. A total of 3558 reports were included in the analysis, with 91 involving exposure to immune checkpoint inhibitors (ICIs) and the remaining reports related to other anticancer drugs. The study sought to evaluate the incidence of adverse pregnancy, fetal, and newborn outcomes associated with ICI exposure compared to alternative anticancer treatments.

The key findings of the study were as follows:

  • The analysis revealed that exposure to immune checkpoint inhibitors (ICIs) during pregnancy did not show an increased risk of specific adverse outcomes compared to other anticancer drugs.

  • The combination of anti-PD1 plus anti-CTLA4 was associated with a significantly higher incidence of preterm birth compared to other anticancer drugs (80.0% vs 23.0%).

  • Rare immune-related neonatal adverse events were identified, underscoring the need for caution in ICI use during pregnancy, particularly with certain combination therapies.

  • These findings highlight the importance of careful risk assessment and monitoring in pregnant patients receiving ICIs.

The study concludes that while exposure to immune checkpoint inhibitors (ICIs) during pregnancy did not demonstrate an increased risk of specific adverse outcomes overall, caution is warranted, particularly with certain combination therapies. Healthcare providers should carefully weigh the potential benefits and risks when considering the use of ICIs in pregnant patients, with a focus on minimizing potential harm to maternal and fetal health. Further research is needed to better understand the risks associated with ICI exposure during pregnancy and to inform clinical practice guidelines and decision-making processes.

Reference:

Gougis, P., Hamy, A.-S., Jochum, F., Bihan, K., Carbonnel, M., Salem, J.-E., Dumas, E., Kabirian, R., Grandal, B., Barraud, S., Coussy, F., Hotton, J., Savarino, R., Marabelle, A., Cadranel, J., Spano, J.-P., Laas, E., Reyal, F., & Abbar, B. (2024). Immune checkpoint inhibitor use during pregnancy and outcomes in pregnant individuals and newborns. JAMA Network Open, 7(4), e245625. https://doi.org/10.1001/jamanetworkopen.2024.5625

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Large-scale genetic study links Irritable Bowel Syndrome and cardiovascular disease

New research published today in the journal Cellular and Molecular Gastroenterology and Hepatology sheds light on disease mechanisms common to irritable bowel syndrome (IBS) and cardiovascular diseases (CVD).

Led by Dr Leticia Camargo Tavares, a Postdoctoral Fellow at the Hypertension Research Laboratory within Monash University’s School of Biological Sciences, the study reveals novel insights into the genetic underpinnings of IBS, offering potential avenues for therapeutic intervention.

IBS is one of the most prevalent gastrointestinal disorders globally, affecting up to 10 per cent of the population, with a disproportionate impact on women.

It is characterised by a complex range of symptoms including abdominal pain, bloating, diarrhea and constipation. IBS significantly compromises patients’ quality of life. Despite its widespread prevalence, the cause of IBS remains unclear, thus limiting treatment options.

An international consortium of researchers, drawing expertise from Monash University (Australia), CIC bioGUNE (Spain), LUM University, IRGB-CNR, CEINGE, and the University of Naples Federico II (Italy), as well as the University of Groningen (Netherlands), embarked on a comprehensive investigation.

Analysing data from two large European population cohorts-UK Biobank and Lifelines-the team scrutinised the genetic landscapes of 24,735 people with IBS and 77,149 symptom-free individuals.

Their analysis uncovered four genomic regions, including two previously unidentified loci, associated with increased susceptibility to IBS.

These genetic hotspots implicate pathways central to gastrointestinal motility, intestinal mucosal integrity, and circadian rhythm regulation.

“Although we’re yet to conclusively pinpoint specific genes and mechanisms, these findings provide novel insights into IBS pathophysiology, highlighting potential therapeutic targets. So, we expect follow-up research to build on these discoveries,” Dr Tavares said.

Moreover, the researchers found a remarkable link between IBS predisposition and various cardiovascular ailments, encompassing hypertension, ischemic heart disease, and angina pectoris.

Professor Mauro D’Amato, senior author and study supervisor from CIC bioGUNE and LUM University, described this new evidence as the most exciting outcome, underscoring the potential for shared therapeutic modalities.

In another important finding, the study revealed that IBS heritability (the weight of genes in determining one’s risk of disease), might be higher than previously thought. This, the authors say, may stem from their adherence to standardised classification criteria in delineating IBS phenotypes, notably the Rome Criteria from the Rome Foundation.

Reference:

Leticia Camargo Tavares et al, Rome III criteria capture higher irritable bowel syndrome SNP-heritability and highlight a novel genetic link with cardiovascular traits, Cellular and Molecular Gastroenterology and Hepatology (2024). DOI: 10.1016/j.jcmgh.2024.04.002.

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Dangerous surgical site infections can be reduced with simple prevention protocol: Study

A new study published today in the American Journal of Infection Control (AJIC) demonstrates the use of a simple pre-surgical infection prevention protocol to prevent dangerous post-surgical infections. Researchers performed this investigation at the Soroka University Medical Center in Israel.

Surgical site infections (SSIs) are a type of healthcare-associated infection with deadly consequences for some patients. According to the latest data from the Centers for Disease Control and Prevention, there were more than 110,000 SSIs linked to inpatient surgeries in the U.S. in 2015.1 These infections lead to a high rate of morbidity and mortality, with a patient’s estimated risk of death as much as 11 times higher than normal.2 SSIs also have a very high financial burden, with the average hospital stay extended by nearly 10 days and an estimated $20,000 in additional hospitalization costs per patient.

There are a number of recommended protocols to help prevent SSIs, but lack of patient compliance, high costs, and bacterial resistance can reduce their utility and effectiveness. In this new study, researchers aimed to evaluate the results of a protocol designed to reduce SSIs through a particular focus on the Staphylococcus aureus pathogen. The approach involved a pre-surgical intranasal application of povidone-iodine and skin antisepsis using chlorhexidine gluconate (CHG).

The study involved 688 adult patients who had hip or knee arthroplasty or spine surgery at Soroka University Medical Center between February 2018 and October 2021. Their outcomes were compared to a retrospective patient cohort from 2016 and 2017 treated before the povidone-iodine component of the protocol was implemented. Patient outcomes were tracked for 90 days after surgery.

Deploying this intervention prior to surgery helped to address a broad challenge in healthcare, that some 30% of the population is colonized with S. aureus without exhibiting symptoms. The pre-surgical protocol successfully eradicated S. aureus in nearly 40% of patients found to already harbor the pathogen. This is particularly important for patient outcomes, as the researchers found that the presence of S. aureus within the day following surgery was associated with a three-fold risk of developing an SSI. Overall, the study showed a significant decrease in severe SSIs among patients who received the newer protocol.

“Our study clearly shows that we can prevent surgical site infections and keep patients safer through the use of a simple pre-surgical nasal application of povidone-iodine in combination with standard CHG bathing,” said Lisa Saidel-Odes, MD, Infectious Diseases specialist at Soroka University Medical Center and lead author of the paper. “We noted that the protocol is most effective in cases with little S. aureus present and suggest that an additional application of the povidone-iodine might be needed for patients with greater nasal colonization.”

Additional details from the study include:

  • Of the 688 patients included, 28 developed an SSI in the 90-day study window. Patients with diabetes were at particularly increased risk for developing an SSI.
  • Patients were screened for S. aureus prior to surgery. More than 16% were already colonized with either methicillin-sensitive or methicillin-resistant S. aureus.
  • Of patients who developed SSIs, S. aureus was not the only cause of infection. Eleven patients were infected with Enterobacterales.

“This study shows the power of applying widely available antiseptics to reduce SSIs and improve patient safety,” said Tania Bubb, PhD, RN, CIC, FAPIC, 2024 APIC president. “The results are encouraging not only because the regimen is effective in reducing SSI, but also because it is simple to implement and avoids the risk of antibiotic resistance.”

Reference:

Lisa Saidel-Odes, Rivka Yosipovich, Vadim Benkovich, Orli Sagi, Orly Shimoni, Abraham Borer, Getting the drop on Staphylococcus aureus: Semiquantitative Staphylococcus aureus nasal colony reduction in orthopedic surgery reduces surgical site infection, American Journal of Infection Control, DOI:https://doi.org/10.1016/j.ajic.2024.02.014.

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Self-Administered Acupressure Reduces Knee Pain in Older Adults with Osteoarthritis, finds study

A new study has revealed that self-administered acupressure (SAA), when combined with brief knee health education, can significantly reduce knee pain in middle-aged and older adults suffering from osteoarthritis (OA). The study results were published in the journal JAMA Network Open.

The effectiveness of self-administered acupressure (SAA) for reducing pain in knee osteoarthritis (OA) among middle-aged and older adults has been largely unexplored until now. This research, which provides promising insights into non-drug treatments for knee OA, was carried out in Hong Kong from September 2019 to May 2022 among community-dwelling individuals aged 50 years and older. The randomized clinical trial involved 314 participants who were either assigned to an intervention group or a control group. The intervention group received two training sessions on how to perform acupressure on themselves and participated in a brief session on knee health education. They were instructed to practice acupressure twice daily over 12 weeks. Meanwhile, the control group received only the knee health education without the acupressure training.
The main measure of the study’s success was the change in participants’ knee pain, assessed using the numerical rating scale (NRS) at the 12-week mark. Secondary outcomes included assessments of physical mobility and quality of life through tools such as the Western Ontario and McMaster University Osteoarthritis Index, the Short Form 6 Dimensions (SF-6D), Timed Up and Go, and Fast Gait Speed tests.
Results at the end of the 12 weeks showed a notable reduction in knee pain for those in the acupressure group, with a mean decrease of 0.54 points on the NRS pain score compared to the control group, marking a significant improvement. Additionally, the SF-6D utility score, which measures aspects of health-related quality of life, also showed a slight increase, suggesting enhanced overall well-being. While the study did not find significant differences between the two groups in other physical mobility tests, the cost-effectiveness acceptability curve highlighted that the intervention has a more than 90% chance of being cost-effective, based on the willingness to pay a threshold of one Gross Domestic Product (GDP) per capita.
The findings of this trial suggest that self-administered acupressure, easily taught through short training sessions and practiced at home, could be an effective and affordable method to alleviate knee pain and improve life quality in those suffering from knee osteoarthritis. This could be particularly valuable for those seeking alternatives to medication for managing their condition.

Further reading: Yeung W, Chen S, Cheung DST, et al. Self-Administered Acupressure for Probable Knee Osteoarthritis in Middle-Aged and Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(4):e245830. doi:10.1001/jamanetworkopen.2024.5830

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Dupilumab Linked to Increased Risk of Cutaneous T Cell Lymphoma in Atopic Dermatitis Patients: Study

Researchers have found that the use of dupilumab, a human monoclonal antibody targeting the IL-4 alpha receptor, is associated with an increased risk of cutaneous T cell lymphoma (CTCL) in patients with moderate to severe atopic dermatitis (AD), according to a study published in the Journal of the American Academy of Dermatology. The study was conducted by Iraj H. and colleagues.

Dupilumab is a commonly prescribed medication for the treatment of moderate to severe atopic dermatitis. It works by targeting the IL-4 alpha receptor, which plays a role in the inflammatory processes associated with the condition. While dupilumab has proven effective for many patients, there have been concerns about its long-term safety, particularly regarding its potential association with cutaneous T cell lymphoma (CTCL).

To investigate the potential link between dupilumab use and the risk of CTCL, researchers used the TrinetX database to compare the incidence of cutaneous and lymphoid malignancies, including CTCL, between a cohort of patients with AD who used dupilumab and a cohort who never used the medication. A secondary analysis was performed excluding patients with prior disease-modifying antirheumatic drug (DMARD) use. Propensity score matching was used to control for potential confounding variables.

The key findings of the study were:

  • An increased risk of CTCL was observed in the cohort of AD patients who used dupilumab, with an odds ratio (OR) of 4.1003 (95% CI, 2.055-8.192).

  • The increased risk persisted even after excluding patients with prior DMARD use.

  • Among other cutaneous and lymphoid malignancies, no increased risk was found.

  • Most of the CTCL cases (27 out of 41) were diagnosed more than one year after the initiation of dupilumab use.

The findings suggest that patients with AD who use dupilumab may have an increased risk of developing CTCL. However, it is important to note that this association does not prove causality. Further research is needed to better understand the potential link between dupilumab use and the development of CTCL, as well as to evaluate the long-term safety of the medication.

The study has several limitations, including potential misclassification within the database and the inability to assess the severity of atopic dermatitis in the patients. As a result, caution should be exercised when interpreting the findings.

In conclusion, the use of dupilumab in patients with atopic dermatitis was associated with an increased risk of cutaneous T cell lymphoma in this cohort study. Although the results indicate a potential safety concern, further research is needed to establish causality and determine the implications for clinical practice.

Reference:

Hasan, I., Parsons, L., Duran, S., & Zinn, Z. (2024). Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: a retrospective cohort study. Journal of the American Academy of Dermatology. https://doi.org/10.1016/j.jaad.2024.03.039

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Clonal hematopoiesis risk score associated mortality risk in older adults with clonal hematopoiesis: JAMA

USA: A recent study published in JAMA Network Open has suggested an association of clonal hematopoiesis (CH) risk score with overall and disease-specific mortality in older adults with CH. Thus, the CH risk score (CHRS) could be used to identify patients with CH who require more intensive surveillance.

The cohort study included 3871 individuals without hematologic malignant neoplasms at baseline, 24.2% had clonal hematopoiesis. The survival of individuals with low-risk CH (59.9% of those with CH) was similar to those without CH, and participants with high-risk CH (6.2% of those with CH) had increased cardiovascular, all-cause, and hematologic malignant neoplasm–related mortality.

With age, clonal hematopoiesis becomes increasingly common. A subset of CH caused by acquired leukemogenic variants is called clonal cytopenia of undetermined significance (CCUS), or CH of indeterminate potential (CHIP), according to the presence or absence of cytopenia. Initially, CCUS/CHIP was described as a risk factor for hematologic (particularly myeloid) malignant neoplasms (HMs). Several studies have demonstrated increased mortality and increased risk of cardiovascular disease, largely among middle-aged adults. However, the predictive value of CCUS/CHIP in the older population is understudied.

Recently, the CH risk score — a prognostic tool that uses complete blood cell count parameters, demographic variables, and molecular features— was developed to estimate myeloid malignant neoplasms risk in CHIP/CCUS patients. Seyedmohammad Saadatagah, Department of Medicine, Baylor College of Medicine, Houston, Texas, and colleagues aimed to examine the prognostic value of CCUS/CHIP in a cohort of older adults (aged ≥65 years) and determine the use of CHRS in estimating disease-specific and overall mortality.

The study included community-dwelling older adults (aged 67-90 years) without hematologic malignant neoplasms who participated in the Atherosclerosis Risk in Communities Visit 5 at 4 US centres. Samples collection was done from 2011 to 2013, sequencing was performed in 2022t, and data analysis was completed in 2023.

The exposure was CH diagnosis, CHRS scores (calculated using eight demographic, molecular factors, and complete cell count) were used to categorize patients with CH into low-risk (CHRS ≤9.5), intermediate-risk (CHRS >9.5 to <12.5), and high-risk (CHRS ≥12.5) groups.

The study’s primary outcome was all-cause mortality, and secondary outcomes included cardiovascular disease mortality and mortality from other causes.

Based on the study, the following inferences were made:

  • Among 3871 participants without a history of HM (mean age, 75.7 years; 58.5% were females), 24.2% had CH.
  • According to the CHRS, 59.9% were low risk, 33.9% were intermediate risk, and 6.2% were high risk.
  • During a median follow-up of 7.13 years, 19.4% of participants without CH and 27.1% of participants with CH died.
  • Mortality by CHRS risk group was 22.8% deaths for low risk, 29.2% for intermediate risk, and 56.9% for high risk.
  • Using multivariable competing risk regression, subdistribution hazard ratios (sHRs) for all-cause mortality were 1.08 for low-risk CH, 1.12 for intermediate-risk CH, and 2.52 for high-risk CH compared with no CH.
  • Among individuals in the high-risk CH group, the sHR of death from HM (10.3% deaths) was 25.58, and that of cardiovascular death (20.7% deaths) was 2.91.

“The findings showed that CHRS was associated with HM-related, all-cause, and cardiovascular disease mortality in older adults with CH,” the researchers wrote, “and may be useful in shared decision-making to guide clinical management and identify appropriate candidates for clinical trials.”

Reference:

Saadatagah S, Uddin MM, Weeks LD, et al. Clonal Hematopoiesis Risk Score and All-Cause and Cardiovascular Mortality in Older Adults. JAMA Netw Open. 2024;7(1):e2351927. doi:10.1001/jamanetworkopen.2023.51927

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