A 47-year-old man presented to the hospital with a 2-day history of weakness and fever. His blood pressure was 64/47 mm Hg, heart rate 110 beats per minute, and temperature 39.0°C. On physical examination, the patient had swelling and redness of the left thigh, which aroused concern about the presence of an abscess. Laboratory studies showed pancytopenia and extreme elevation of the d-dimer level. Promyelocytic blast cells with intracellular Auer rods — needle-shaped cytoplasmic structures specific for myeloid neoplasms — were seen on a peripheral-blood smear. Owing to concern about acute promyelocytic leukemia and sepsis, the patient was admitted to the intensive care unit. Induction chemotherapy with all-trans retinoic acid and prednisolone was initiated. A bone marrow biopsy showed promyelocytes with abundant intracellular Auer rods in formations that resembled bundles of sticks (arrows). Genetic analysis for chromosomal translocation identified a PML–RARA fusion gene. A diagnosis of acute promyelocytic leukemia was confirmed. Two days after the start of treatment, differentiation syndrome developed. The hospital course was further complicated by the presence of disseminated intravascular coagulation and Staphylococcus aureus bacteremia with leg abscesses. After molecular complete remission had been attained, consolidation chemotherapy that included arsenic trioxide was administered. On hospital day 72, the patient was discharged.
A 57-year-old woman with a history of depression and insomnia presented to the emergency department with a 3-day history of shortness of breath and dizziness. The physical examination was notable for pallor. Laboratory studies showed a hemoglobin level of 4.4 g per deciliter (reference range, 11.6 to 15.5), an elevated reticulocyte count, an elevated lactate dehydrogenase level, and a low haptoglobin level. The results of hemoglobin electrophoresis and glucose-6-phosphate dehydrogenase testing were normal, and methemoglobin and direct antiglobulin tests were negative. A peripheral-blood smear (Panel A, Giemsa staining) showed poikilocytosis, nucleated red cells (black arrows), and polychromatic cells (white arrows). The findings were also consistent with oxidative hemolysis, including the presence of bite cells (Panel A, red arrows), blister cells (Panel A, asterisks), and erythrocyte inclusions (Panel B, Giemsa staining). The erythrocyte inclusions were identified as Heinz bodies on the basis of positive staining with methyl violet (Panel C). Blood transfusions were administered. After a prolonged toxicologic investigation that involved multiple readmissions over the course of the next 7 months, the patient eventually reported having taken 10 times the recommended daily dose of zopiclone (a nonbenzodiazepine hypnotic) every night to treat insomnia since 1 month before the first presentation. Urine drug testing was positive for zopiclone. A diagnosis of drug-induced oxidative hemolysis was made. The patient was counseled to cease zopiclone use and was referred to psychiatry for treatment.
Summary: A new study aims to examine the role of napping in brain development among infants and preschoolers. By tracking changes in the hippocampus, the research aims to prove how critical naps are for memory retention and brain growth in young children.
These longitudinal studies could set new standards for nap policies in educational settings, benefiting both neurotypical and neurodiverse children. Insights from this research will provide valuable guidelines for parents and educators on the importance of napping in early childhood.
Key Facts:
Focus on the Hippocampus: The studies investigate the hippocampus’s role during nap transitions, highlighting its significance in short-term memory and overall brain development.
Longitudinal Approach: Unlike previous cross-sectional studies, these projects will observe the same children over time to better understand the developmental milestones associated with napping.
Practical Applications: Findings from the studies are expected to influence nap policies in preschool environments and offer actionable insights for parents of young children.
Source: UMass
A University of Massachusetts Amherst sleep scientist, funded with $6.7 million in grants from the National Institutes of Health (NIH), has launched two unprecedented studies that will track over time the brain development of infants and preschoolers to confirm the role of napping in early life and to identify the bioregulatory mechanisms involved.
Rebecca Spencer, a professor of psychological and brain sciences who is well-known for her groundbreaking research into napping, is testing her theories about what’s happening in the hippocampus–the short-term memory area of the brain–as babies and young children undergo nap transitions.
Naps allow children with an immature hippocampus to process memories. Credit: Neuroscience News
This new research is expected to become the gold standard of scientific evidence that emphasizes the importance of healthy sleep for young children as their brains develop.
The findings will help inform nap policies for preschool and pre-kindergarten and be useful to teachers and parents of both neurotypical and neurodiverse children.
“The work we’ve been doing has always pointed to this interaction of sleep and brain development,” says Spencer, who carries out research in her Somneurolab at UMass Amherst.
“We think that kids get ready to transition out of naps when the brain is big enough to hold all the information of the day until night-time sleep.”
The study involving preschoolers is a collaboration between Spencer at UMass Amherst; Tracy Riggins, a developmental psychologist specializing in memory development at the University of Maryland; and Gregory Hancock, a UMD professor of human development and quantitative methodology.
Previous research by Spencer and Riggins showed differences in the hippocampus of kids who nap compared to those who have transitioned out of naps.
“So far, we’ve used cross-sectional approaches,” says Spencer, referring to research that analyzes data at one point in time, as opposed to longitudinal studies that involve repeated observation over time.
“We really need to show longitudinally within a child that the point when they transition out of naps is predicted by a transition in the development of their hippocampus.”
The hippocampus is the short-term location for memories before they move to the cortex for long-term storage. Naps allow children with an immature hippocampus to process memories.
Young children give up their afternoon nap, not based on their age, but their brain development, Spencer hypothesizes.
“Naps are beneficial to everybody. Naps protect memory for everybody, no matter what age. Kids who are habitual nappers really need the nap. If they don’t nap, they get catastrophic forgetting.
“That’s the difference between habitual and non-habitual nappers – not how good is the nap, but how bad is staying awake,” Spencer explains.
Adds Riggins, “In the end, being able to tell parents that those little deviations from routine that keep their children from napping might not have these huge implications for a neurotypical child in the long run would be great.
“And, the more we know about how the brain works in a typically developing child during this nap transition, the more we will be able to know about where we could possibly intervene to help neurodiverse children–like children with autism and ADHD, whose sleep patterns tend to be disrupted–since we will have some sort of scientific basis.”
The research team is recruiting 180 children, ages 3 to 5 years. The researchers will track their brain development, memory performance and nap status over the course of one year at three checkpoints.
During the first and second sessions, the children will wear activity-tracking watches and EEG equipment to record naps and overnight sleep. They will also play memory games before and after naps. The children will undergo an MRI brain scan during the third session.
Monica and David Dumlao, of Chicopee, Mass., signed up their son Miles, 4, for the preschool study after watching the Netflix documentary series, “Babies,” which featured Spencer in the episode about sleep.
“We like learning about the neuroscience behind brain development,” Monica Dumlao said at a recent study session in Spencer’s lab.
“We thought this was a good opportunity to contribute to the science about the importance of naps.”
In the three-part infant study on nap transitions and memory, Spencer is studying the period before and after babies transition from two naps–one in the morning and one in the afternoon–to one, richer afternoon nap.
She is recruiting 140 infants 7 to 9 months old. The babies will play a memory game before and after their naps. Their brain activity will be recorded during their naps using a noninvasive electrode cap. The sessions will take place at 9, 12 and 15 months.
“We think as they are getting ready to drop the morning nap, staying awake in that morning interval will be less and less damaging to their memory,” Spencer says.
“But we don’t think that’s going to happen with the afternoon nap at this age. We think the afternoon nap stays superimportant.”
Summary: Vitamin D enhances a type of gut bacteria in mice, improving their immunity to cancer. The study shows that mice with higher levels of vitamin D resist tumor growth better and respond more effectively to immunotherapy.
This effect seems linked to the increase of Bacteroides fragilis in the gut, which somehow enhances the mice’s immune response to cancer. Further research is needed to see if this applies to humans, as earlier studies suggest a potential link between vitamin D levels and cancer risk.
Key Facts:
Vitamin D Role: Mice fed with vitamin D exhibited increased levels of Bacteroides fragilis, which helped them resist cancer better.
Human Implications: Preliminary data analysis from 1.5 million people in Denmark hints at a correlation between low vitamin D levels and higher cancer risk.
Future Research: Understanding how vitamin D can be utilized to boost the beneficial gut microbiome could open new pathways for cancer treatment and prevention.
Source: Francis Crick Institute
Researchers at the Francis Crick Institute, the National Cancer Institute (NCI) of the U.S. National Institutes of Health (NIH) and Aalborg University in Denmark, have found that vitamin D encourages the growth of a type of gut bacteria in mice which improves immunity to cancer.
Reported today in Science, the researchers found that mice given a diet rich in vitamin D had better immune resistance to experimentally transplanted cancers and improved responses to immunotherapy treatment.
This effect was also seen when gene editing was used to remove a protein that binds to vitamin D in the blood and keeps it away from tissues.
Surprisingly, the team found that vitamin D acts on epithelial cells in the intestine, which in turn increase the amount of a bacteria called Bacteroides fragilis. This microbe gave mice better immunity to cancer as the transplanted tumours didn’t grow as much, but the researchers are not yet sure how.
To test if the bacteria alone could give better cancer immunity, mice on a normal diet were given Bacteroides fragilis. These mice were also better able to resist tumour growth but not when the mice were placed on a vitamin D-deficient diet.
Previous studies have proposed a link between vitamin D deficiency and cancer risk in humans, although the evidence hasn’t been conclusive.
To investigate this, the researchers analysed a dataset from 1.5 million people in Denmark, which highlighted a link between lower vitamin D levels and a higher risk of cancer.
A separate analysis of a cancer patient population also suggested that people with higher vitamin D levels were more likely to respond well to immune-based cancer treatments.
Although Bacteroides fragilis is also found in the microbiome in humans, more research is needed to understand whether vitamin D helps provide some immune resistance to cancer through the same mechanism.
Caetano Reis e Sousa, head of the Immunobiology Laboratory at the Crick, and senior author, said: “What we’ve shown here came as a surprise – vitamin D can regulate the gut microbiome to favour a type of bacteria which gives mice better immunity to cancer.
“This could one day be important for cancer treatment in humans, but we don’t know how and why vitamin D has this effect via the microbiome. More work is needed before we can conclusively say that correcting a vitamin D deficiency has benefits for cancer prevention or treatment.”
Evangelos Giampazolias, former postdoctoral researcher at the Crick, and now Group Leader of the Cancer Immunosurveillance Group at the Cancer Research UK Manchester Institute, said: “Pinpointing the factors that distinguish a ‘good’ from a ‘bad’ microbiome is a major challenge. We found that vitamin D helps gut bacteria to elicit cancer immunity improving the response to immunotherapy in mice.
“A key question we are currently trying to answer is how exactly vitamin D supports a ‘good’ microbiome. If we can answer this, we might uncover new ways in which the microbiome influences the immune system, potentially offering exciting possibilities in preventing or treating cancer.”
Romina Goldszmid, Stadtman Investigator in NCI’s Center For Cancer Research, said: “These findings contribute to the growing body of knowledge on the role of microbiota in cancer immunity and the potential of dietary interventions to fine-tune this relationship for improved patient outcomes.
“However, further research is warranted to fully understand the underlying mechanisms and how they can be harnessed to develop personalized treatment strategies.”
This research was funded by Cancer Research UK, the UK Medical Research Council, the Wellcome Trust, an ERC Advanced Investigator grant, a Wellcome Investigator Award, a prize from the Louis-Jeantet Foundation, the Intramural Research Program of the NCI, part of the National Institutes of Health, CCR-NCI and the Danish National Research Foundation.
Research Information Manager at Cancer Research UK, Dr Nisharnthi Duggan said: “We know that vitamin D deficiency can cause health problems, however, there isn’t enough evidence to link vitamin D levels to cancer risk.
This early-stage research in mice, coupled with an analysis of Danish population data, seeks to address the evidence gap. While the findings suggest a possible link between vitamin D and immune responses to cancer, further research is needed to confirm this.
“A bit of sunlight can help our bodies make vitamin D but you don’t need to sunbathe to boost this process. Most people in the UK can make enough vitamin D by spending short periods of time in the summer sun.
“We can also get vitamin D from our diet and supplements. We know that staying safe in the sun can reduce the risk of cancer, so make sure to seek shade, cover up and apply sunscreen when the sun is strong.”
Abstract
Vitamin D regulates microbiome-dependent cancer immunity
A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies.
Similarly, in humans, vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival.
In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity.
Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer.
Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.
A retrospective evaluation of I-SPY2 clinical trial data indicates that in appropriately selected patients with breast cancer, sentinel lymph node surgery with adjuvant radiation may provide appropriate oncologic control without the routine use of axillary dissection. Judy C. Boughey, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues presented their results during the 2024 Society of Surgical Oncology (SSO) Annual Meeting (Abstract 3). Although follow-up in the I-SPY2 cohort thus far is fairly short (median, 3.5 years), they found that compared with selective use of sentinel lymph node surgery alone after neoadjuvant chemotherapy, axillary dissection did not improve axillary recurrence, locoregional recurrence, distant recurrence, or event-free survival—even in patients with node-positive disease.
They evaluated the outcomes of patients—those who did and did not have residual nodal disease—who underwent axillary surgery after neoadjuvant chemotherapy between 2011 and 2022. Axillary surgery was classified as sentinel lymph node surgery alone or as axillary dissection (with or without sentinel lymph node surgery).
Slightly more than 1,500 patients were included: 714 (47.1%) had clinically node-negative disease at diagnosis, of whom 104 (14.6%) had pathologically node-positive disease; 801 (52.9%) had clinically node-positive disease at diagnosis, of whom 396 (49.4%) had pathologically node-positive disease. Sentinel lymph node surgery alone was performed in 805 of 1,015 (79.3%) patients with pathologically node-negative disease and in 126 of 500 patients (25.2%) with pathologically node-positive disease.
Dr. Boughey and co-investigators found that among patients who had pathologically node-negative disease, no significant differences occurred between those who underwent sentinel lymph node surgery alone and those who had axillary dissection in the 5-year estimated rate of axillary recurrence, locoregional recurrence, distant recurrence, and event-free survival. Among patients who had pathologically node-positive disease, there was no difference between sentinel lymph node surgery alone and axillary dissection in the 5-year estimated axillary recurrence or locoregional recurrence.
BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known.
METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients’ assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment.
RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration.
CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages.
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