Tag: Sweden

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Pregnancy Complications Increase the Risk of Peripheral Artery Disease

Having a common birth complication such as preterm birth, preeclampsia, high blood pressure and gestational diabetes puts women at increased risk of developing peripheral artery disease in later life.

As reported in PLOS Medicine, all five of the common complications listed were associated with an increased risk for peripheral artery disease, a form of atherosclerosis in the legs, up to 46 years after giving birth in a large Swedish study.

Overall, women with gestational diabetes had almost four-times higher risk of developing peripheral artery disease than women who had a healthy pregnancy with preeclampsia, high maternal blood pressure, preterm birth or small for gestational age babies increasing risk 1.3–1.7-fold.

“Peripheral artery disease affects more than 230 million people worldwide and is a strong predictor of future stroke, ischemic heart disease, and premature mortality,” write Casey Crump, MD, PhD, an epidemiologist and family physician at McGovern Medical School, and colleagues.

“Despite its high prevalence and clinical importance, it is understudied compared with other cardiovascular diseases.”

Pregnancy complications such as gestational diabetes and preeclampsia are known to increase the risk of other types of cardiovascular disease so Crump and team carried out a study to assess if this was also the case for peripheral artery disease.

The team drew on Swedish national birth and health registries to follow more than 2.2 million women who had single‑baby pregnancies between 1973 and 2015. They focused on the five common birth complications and tracked new diagnoses of peripheral artery disease from hospital, specialist clinic, and primary care records for up to 46 years after childbirth.

The researchers compared women with and without these complications while accounting for age, education, income, smoking, weight, and existing conditions like hypertension or diabetes. The also compared sisters to check whether shared genes or family lifestyle could fully explain the patterns they saw.

Overall, 13,211 women developed peripheral artery disease, mostly in their early 60s. All the complications were linked to higher risk of arterial disease, with the association becoming stronger with age. Experiencing more than one complication also increased risk further and women with three or more had around three times higher risk of peripheral artery disease in later life than women with none. The research also showed links were not likely to be genetic or related to a shared upbringing.

“Women who experience an adverse pregnancy outcome need early preventive actions and long-term clinical follow-up to reduce their risk for peripheral artery disease and other associated cardiovascular diseases,” write the authors.

The post Pregnancy Complications Increase the Risk of Peripheral Artery Disease appeared first on Inside Precision Medicine.

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Epigenomic Analysis Uncovers New AML Subgroups and Drug Sensitivities

As one of the most aggressive blood cancers, the way acute myeloid leukemia (AML) is classified continues to shape every major clinical decision—from risk stratification to the choice of targeted therapies. For decades, that classification has rested almost entirely on the gene mutations found in leukemic cells. But mutations alone have never fully explained why AML behaves so differently from patient to patient. A new study published in Nature now provides the missing layer: the epigenome.

In the largest chromatin‑profiling effort ever conducted for any cancer, a research team led by Seishi Ogawa, MD, PhD, and Yotaro Ochi, MD, PhD, of Kyoto University, together with Sören Lehmann, MD, PhD, of the Karolinska Institute, mapped the chromatin accessibility landscape of 1,563 AML patient samples. Their analysis—built on ATAC‑seq, RNA‑seq, DNA methylation, ChIP‑seq, whole‑genome sequencing, and single‑cell multiomics—reveals that AML can be classified into 16 distinct epigenomic subgroups, each defined by a characteristic chromatin state and its own regulatory wiring.

As the authors wrote, “ATAC-seq…show[s] that AML can be classified into 16 subgroups on the basis of chromatin accessibility profiles.” This chromatin‑based structure was remarkably stable: single‑cell ATAC‑seq across more than 280,000 cells confirmed that each patient’s leukemic population shares a conserved accessibility fingerprint.

Each subgroup carries a unique combination of driver mutations, differentiation states, transcription‑factor networks, DNA methylation patterns, and super‑enhancer architecture. Many do not align cleanly with existing genomic classifications such as WHO or ICC, according to the researchers. In fact, the team found that even exhaustive decision‑tree analyses of known driver mutations could not explain most subgroup identities. As the paper noted, “Evidence suggests that genetic alterations do not fully explain AML pathophysiology and heterogeneity.”

Clinically, chromatin information sharpened prognostic assessment in both Swedish and Japanese cohorts. Several subgroups also showed unexpected drug sensitivities. Three subgroups responded to MEK inhibitors despite lacking RAS‑pathway mutations. Another subgroup, enriched for RUNX1 mutations and marked by a chromatin profile resembling early B‑cell precursors, proved highly sensitive to ABL inhibitors.

The study, “Chromatin landscape and epigenetic heterogeneity of acute myeloid leukemia,” positions chromatin architecture as a foundational dimension of AML biology. It also provides a practical path toward clinical adoption: the team distilled a 30‑gene expression signature capable of identifying high‑risk chromatin subgroups using standard sequencing workflows.

Looking ahead, the group aims to develop lower‑cost diagnostic approaches and refine treatment strategies tailored to each epigenomic subgroup. The newly generated eCHROMA AML atlas is expected to serve as a resource for cancer epigenomics broadly, enabling discovery of new therapeutic targets and mechanistic insights.

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Stem Cell Therapy Shows Promise in First Human Parkinson’s Disease Trial

A landmark Phase I/II clinical study led by researchers at Skåne University Hospital and Lund University has shown that transplanting stem-cell-derived dopamine progenitor cells into the brain is feasible. Eight patients with Parkinson’s disease (PD) received transplants of STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. The three-year Phase I/II, open-label, multicenter, single-arm, dose-escalation study identified no serious side effects linked to the transplanted cells during the first year of follow‑up.

“The possibility of replacing dopamine neurons that are lost in Parkinson’s disease has been a long-standing goal in the field,” said Malin Parmar, professor of cellular neuroscience at Lund University, and lead of the STEM-PD program. “The findings represent an important milestone for regenerative medicine approaches in Parkinson’s disease and support continued clinical development of stem cell-based therapies.”

Results from the study were reported by Parmar and colleagues in Nature Medicine. In their paper, titled “Human embryonic stem cell-derived dopaminergic cells for Parkinson’s disease: a Phase I/II open-label trial,” the team wrote, “In conclusion, particularly in the context of other recently published trials using human PS cell-derived dopaminergic cell therapies for PD, these findings further support the continued development of this therapeutic approach, including evaluation of the STEM-PD product in larger patient cohorts.”

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, the authors wrote. In Parkinson’s disease, patients lose nerve cells in the brain that produce dopamine, which leads to symptoms such as slowness of movement, stiffness, gait disturbance, and tremor. “The hallmark pathology of PD involves progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the subsequent loss of their projections to the striatum,” the team explained. Current treatments are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects.

“Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD,” the investigators continued. Scientists have been working to develop standardized and scalable dopamine cell therapy products derived from pluripotent stem (PS) cells, including human embryonic stem (ES) cells and induced PS (iPS) cells, they noted. “Several such products are now in clinical development … with early safety and feasibility data emerging.”

The transplanted stem cell-based dopamine nerve cell product tested in the newly reported trial is designed to replace the cells that produce dopamine, and the goal is that after being transplanted, the transplanted cells will mature into new dopamine-producing nerve cells in the brain. The STEM-PD trial aimed to evaluate the safety, tolerability, and feasibility of intraputaminal transplantation of STEM-PD in patients with moderately advanced PD.

Eight individuals with Parkinson’s disease received the transplanted cell product at two different doses, followed by 12 months of immunosuppression to prevent graft rejection. All patients were treated at Skåne University Hospital. Seven participants completed 12-month follow-up, and one participant died from a pulmonary infection that was not directly related to the cell product.

The surgical procedure was generally well tolerated, and no graft-induced involuntary movements were observed in the transplanted participants. Clinically, patients remained stable. Imaging using dopamine PET scans provided early indications of graft survival at both 6 and 12 months post-transplantation. Six of the seven participants substantially reduced their dopaminergic medication, a result that will be evaluated over time. In their paper, the team wrote in summary, “This Phase I/II clinical trial involving the bilateral intraputaminal transplantation of the STEM-PD dopaminergic progenitor cell product demonstrates its feasibility with no unexpected safety concerns from the cell product.”

Roger Barker, MD, professor of clinical neuroscience at the University of Cambridge, clinical lead of STEM-PD and clinical PI at the U.K. site, said: “This represents an exciting new departure on repairing the brain of individuals with Parkinson’s using dopamine cells- an approach pioneered in Lund some 40 years ago using fetal dopamine cells. The STEM-PD trial harnessing the expertise of scientists and clinicians from Lund and Cambridge has enabled us to undertake and deliver on one of the first ever stem cell-derived dopamine cell therapies for patients with Parkinson’s, and we hope this will be the beginning of an exciting new programme that may ultimately benefit the wider Parkinson’s community.”

Gesine Paul-Visse, MD, professor in neuropsychiatric research and lead PI at Skåne University Hospital, said, “Reaching this primary endpoint and being able to show that the cell product is safe is a great achievement for this trial, our team, the participating patients, but also for all patients suffering from Parkinson’s disease. We are hopeful that the early signs of cell survival and clinical improvement we observe will continue to increase over time and are excited to continue the development of this cell therapy.”

The STEM-PD research team will now continue the long-term follow-up of the participants to further evaluate safety, graft function, and clinical benefit. “Secondary and exploratory outcomes will evaluate the course and efficacy of clinical features, the survival of grafted dopaminergic cells at 36 months as well as additional safety signals occurring between 12 and 36 months and any dose–response effects,” the investigators stated. “Further evaluation of the grafts up to 36 months will determine whether the implanted cells continue to grow, mature and reinnervate the putamen after 12 months.”

STEM-PD builds on decades of research in dopamine cell replacement therapy for PD at Lund University and pioneering work in translation of pluripotent stem cell technology from experimental studies into clinical evaluation. The STEM-PD trial is the first pluripotent stem cell trial approved in Sweden and the first for PD in Europe. “The initiation and execution of this clinical trial have only been possible through close collaboration between scientists, clinicians, GMP manufacturing teams, regulatory experts and, most importantly, the participating patients,” concluded Parmar. In their report, the authors stated, “The STEM-PD trial adds further important confirmatory and complementary evidence to the recently reported feasibility and short-term safety of PS cell-derived dopaminergic progenitor transplantation in PD.”

The academic Phase I/IIa trial was conducted in collaboration with Novo Nordisk. Cellular Intelligence, a Boston-based company, recently acquired the STEM-PD program and will lead its next phase of clinical development, including a planned Phase II trial. The STEM-PD cells and their continued development hold IND clearance with FDA Fast Track Designation, and Cellular Intelligence aims to advance the program through Phase III to market approval.

STEM-PD is an academic European clinical translation initiative, focused on developing stem cell-based therapies for Parkinson’s disease. The program is led from Lund University with partners from Skåne University Hospital, Cambridge University Hospital, and University College London and combines expertise in stem cell biology, GMP manufacturing, neurosurgery, clinical neurology, and regenerative medicine to advance pluripotent stem cell-derived dopamine neuron therapies toward clinical application.

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Access to an mHealth Tool for Symptom Management in Pediatric Oncology Care: Triangulation Study

Background: Digital health offers opportunities to facilitate symptom assessments and communication for children with cancer, particularly after discharge. However, access to these tools must be established to ensure that they effectively support the user. PicPecc (Pictorial Support in Person-Centered Care for Children) is a mobile health tool developed to enable children to remotely assess symptoms and communicate with health care professionals. Understanding access to PicPecc is essential for evaluating its use in pediatric oncology. Objective: The aim was to test a digital intervention with PicPecc in pediatric oncology care through the lens of access to technology. Methods: This study uses a triangulation approach to determine access to digital technology through an intervention, PicPecc outside hospital. Fourteen children (6‐17 y), 5 parents, and 6 nurses from 2 pediatric oncology units in Sweden participated. Children were encouraged to use PicPecc for 2 weeks (achieving a median of 14, IQR 9.75-16 days) following hospital discharge to assess pain, nausea, sleep disturbances, and feelings using an assessment scale, pictures, personal notes, and a chat function. Nurses monitored assessments and responded via the administrative interface. Access was analyzed through interviews and an instrument, and by recording the consumption of PicPecc. Data analysis was based on the 5 dimensions of access (availability, accessibility, accommodation, affordability, and acceptability). Results: The intervention, PicPecc outside hospital, supported availability by enabling children to communicate symptoms in a safe and structured way. Children and parents mentioned feeling safe when they were discharged from the hospital, and nurses perceived it as a valuable complement to follow-up after discharge. PicPecc outside hospital was generally accessible, although initial challenges with log-in procedures related to the PIN code were common. Barriers related to accommodation included interpreting the scale and obtaining an overview of assessments. Affordability was high, as internet access and device availability were not barriers; however, children’s motivation varied depending on symptom burden. Acceptability was strong among children up to 12 years of age, who appreciated the design and gaming function, while the older children found the visual design less age-appropriate. Conclusions: Access to the mobile health tool, PicPecc outside hospital, appears promising for supporting remote symptom assessment in pediatric oncology, particularly among children up to 12 years of age. However, identified barriers, such as motivational factors and integration into the health care system, need to be addressed.
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Stockholm3 Blood Test Detects More High-Risk Prostate Cancers Early 

A new blood test may help address one of the key challenges in prostate cancer detection—identifying aggressive forms of the disease early on. According to research led by a team at Karolinska Institutet, the Stockholm3 blood test detected more clinically significant cancer cases than the well-established, but problematic, Prostate Specific Antigen (PSA) screening test. 

The study appears in the Annals of Internal Medicine. Swedish researchers collaborated with teams from Europe and the U.S. on this work.

Prostate cancer is one of the top cancers among men globally, with an estimated 1.5 million new cases and 397,000 deaths annually. PSA testing has long been used for early detection. But, although PSA is prostate-specific, it is not cancer-specific. Elevated PSA levels can be caused by benign conditions as well as cancer and up to 50% of diagnosed aggressive prostate cancers are in men with low PSA values—below today’s cutoffs of PSA 3 ng/ml or PSA 4 ng/ml.

“There are a number of tests in development to improve on PSA alone. A lot of them, like Stockholm3, are fairly ingenuous and do a good job,” Mark Pomerantz told Inside Precision Medicine. He is a medical oncologist at the Dana-Farber Cancer Institute in Boston. Until one of these newer tests emerges as a winner, though, MRI is the gold standard for evaluating men with high PSA. “With MRI we can see the prostate in some detail,” Pomerantz said, “But it is expensive.”

The Karolinska-led researchers analyzed data from 12,670 men aged 50–74 from the population-based STHLM3-MRI study, which compared MRI-targeted and standard biopsy in men with elevated PSAs. In this more recent Annals study, the men were tested first with both PSA and Stockholm3 and followed for two years via national cancer registries, which allowed researchers to also identify cancer cases missed during the initial screening.

Stockholm3 detected 90 percent of aggressive cancer cases, compared to 74 percent for PSA.

“The test incorporates plasma protein biomarkers, genetic risk information from a polygenic risk score, and clinical factors such as age, family history, and prior biopsy history,” the study’s lead author Thorgerdur Palsdottir, told Inside Precision Medicine. Palsdottir is a researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. 

He added, “Together, these components provide a more comprehensive estimate of a risk of harboring clinically significant prostate cancer than PSA alone.” 

The components, he explained, map onto distinct biological axes rather than a single one. The kallikreins (PSA, free PSA, hK2) reflect prostate epithelial and tumor secretory activity, and the free-to-total PSA relationship helps separate benign enlargement from cancer. The polygenic score and family history capture inherited susceptibility—a man’s baseline predisposition—rather than anything about a tumor. GDF-15 is a stress-response marker that has been associated with more aggressive disease across several cancers. 

During the study follow-up, 443 men were diagnosed with clinically significant, i.e. aggressive, prostate cancer. Stockholm3 missed significantly fewer serious cancer cases than PSA, while the proportion of men incorrectly classified as high-risk was similar between the tests.

“These results point toward a potential change in how prostate cancer screening can be conducted. A more precise blood test could enable earlier detection of aggressive disease while reducing the number of unnecessary follow-up examinations and procedures,” said Palsdottir.

He adds that longer-term follow-up is needed to fully assess the effects on mortality and long-term outcomes. “The next important step is to evaluate longer-term outcomes, including disease progression, metastatic disease, and prostate cancer mortality.”

The post Stockholm3 Blood Test Detects More High-Risk Prostate Cancers Early  appeared first on Inside Precision Medicine.

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Framework for Health-Promoting Environments for Office Workers: Photovoice Study

Background: Office work is increasingly carried out outside conventional office settings, particularly during and after the COVID-19 pandemic. This highlights the need to understand the complexity of aspects that may influence health across different office work environments. Objective: This study aimed to (1) identify aspects that office workers perceive as supporting or hindering their health during office work, and (2) formulate novel questions about office work for quantitative studies. Methods: In February 2021, we conducted a digitally distributed photovoice study in Sweden, in which a convenience sample of 17 office workers from 5 companies took photos and provided written comments on what they perceived as supporting or hindering their health in places where they performed office work. For objective 1, we carried out both qualitative formal analysis and analysis without a theoretical frame, as well as quantified the content of the photos and comments. The identified aspects and their interactions were summarized in a visual framework. For objective 2, findings from the photovoice study were used to adapt selected items from the 2019 Swedish Work Environment Survey, capturing office work performed across multiple settings. Results: Of a total of 63 photos, 70% (44/63) were taken at home, 24% (15/63) in an office, and 6% (4/63) outdoors. The comments on photos taken in conventional office settings largely highlighted health-promoting aspects, while the interpretations of home office photos showed greater variability regarding their impact on health. We identified 9 aspects and categorized them into two groups: (1) environmental perspective, including space, ergonomic, technical, and aesthetic-sensuous aspects and (2) behavioral perspective, including flexibility, focus, breaks-recovery, physical activity, and eating habits. Whether the aspects supported or hindered health depended on the environment where office work was performed and the employees’ living conditions. Our visual framework illustrates how these two perspectives interact with each other, bridged by space and flexibility. The study also resulted in a battery of multiple-choice questions about work in offices, at home, in public places, and outdoors that can be used in future research to better capture variation in modern work arrangements. Conclusions: This study extends the notion that office environments play a central role in supporting employee health by suggesting that this also applies to home offices. The results emphasize the need for tailored health-promoting interventions that account for the diverse environments in which office work is performed and for individual needs. The developed visual framework for analyzing health-promoting work environments for office workers and the battery of survey questions can contribute to future research and the advancement of sustainable, health-promoting office environments.
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STAT+: Moderna co-founder Kenneth Chien on the future of mRNA — and Moderna 

Among all the awards and mementos Moderna co-founder Kenneth Chien has accumulated over a 50-year career in science, one stands out for its sheer luxe: an Hermes belt.

It was a 2013 gift from Moderna CEO Stéphane Bancel, one of biotech’s more dapper CEOs, after Chien helped secure a large partnership between the then-tiny mRNA startup and the Swedish-British pharmaceutical giant AstraZeneca. 

The deal accelerated Moderna’s ascent, helping bring billions in funding and of course the life-saving mRNA Covid vaccines. But the actual medicines AstraZeneca planned to build through those deals — up to 40 mRNA-based drugs for cancer and cardiovascular disease — never materialized. 

Continue to STAT+ to read the full story…

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Single Psilocybin Dose Relieves Depression for Over Three Months

Researchers in Sweden report that a single dose of psilocybin, a psychedelic compound found in mushrooms, can provide rapid relief from depressive symptoms. Results from a small-scale Phase II trial, published today in JAMA Network Open, show that patients experienced an improvement as soon as two days after treatment, with effects persisting for longer than three months. 

”Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important,” says Hampus Yngwe, MD, consultant psychiatrist and PhD student at the department of clinical neuroscience of the Karolinska Institutet in Stockholm. 

Major depressive disorder is commonly treated with selective serotonin reuptake inhibitors (SSRIs), but most patients do not respond to this treatment or become resistant. In addition, their effects can typically take several weeks to be noticeable, and side effects are common. 

Previous research had shown that a single dose of psilocybin can have antidepressant effects in people with treatment-resistant depression or anxiety disorders in patients with advanced cancer. The current study looked instead at the effects of this compound on “common” forms of major depressive disorder. 

The study recruited a total of 35 people with moderate to severe recurrent depression, between 20 and 65 years of age. They were randomly assigned to receive either a single 25mg dose of psilocybin or niacin, an active placebo that causes a noticeable physical reaction. All patients received psychotherapeutic support before, during, and after treatment.  

Participants were evaluated using the Montgomery–Åsberg depression rating scale (MADRS) to assess treatment effects at multiple time points after dosing. After a week, the group who received psilocybin saw an average MADRS score reduction of 9.7 points, compared to 2.4 points in the placebo group, and these effects persisted after two weeks and six weeks. At this point, 53% of participants who received psilocybin were in remission, compared to 6% in the placebo group. 

A self-reported version of the MADRS revealed that patients saw antidepressant effects as early as day two after dosing, and continued to experience these positive effects for over three months. 

A year after treatment, all patients who received psilocybin treatment remained in remission. However, many of the patients who received the placebo had also recovered at that point, showing no major statistical difference between both groups. 

“The long-term effects are uncertain,” says Yngwe. “Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies.”

Because the effects of psilocybin are strong and easily recognizable, many participants were able to tell whether they had received the treatment or the placebo. This is a common challenge scientists face when studying psychedelic treatments that can make it difficult for patients and researchers alike to separate the effects of the treatment from their expectations. “We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” notes Yngwe.

Next, the researchers will analyze data from PET scans, blood, and cerebrospinal fluid samples collected from all patients before and after dosing. This will help them understand the physiological changes induced by psilocybin, and how these influence its observed antidepressant effects. 

”Research suggests that the interaction between parts of the brain is impaired in depression and that this may be linked to changes in the connections between nerve cells, known as synapses,” says Yngwe. “In preclinical studies, psychedelics have been shown to stimulate synaptic growth. We therefore want to investigate whether psilocybin alters synaptic density in the brain.”

The post Single Psilocybin Dose Relieves Depression for Over Three Months appeared first on Inside Precision Medicine.