Results from a new trial indicate that immunotherapy could successfully be used to treat the most common form of colorectal cancer, also known as bowel cancer.
The findings of the new study, a phase 1 trial involving the immunotherapy drugs botensilimab and balstilimab, have been published in the journal Nature Medicine, and it is the first time that consistent and durable responses to immunotherapy have been reported in difficult-to-treat patients.
Co-authored by Professor Justin Stebbing of Anglia Ruskin University (ARU), who describes the results as “potentially game changing,” the study focused on the most common type of colorectal tumours, known as MSS mCRC, or microsatellite stable metastatic colorectal cancer.
Although immunotherapy has previously been shown to work on patients with specific mismatch repair deficient (dMMR) tumours, only a small percentage of colorectal cancer patients have this type of tumour, and immunotherapy has so far been ineffective in patients with more common MSS mCRC tumours.
The new study involved using the immunotherapy drug botensilimab in conjunction with balstilimab on a group of patients in the United States. These drugs are both monoclonal antibodies, which work by triggering the body’s immune system to attack the cancer.
Of the patients in the phase 1 trial, 101 took part in a six-month follow-up and of these, 61% of them saw their tumour shrink or remain stable after receiving a combination of botensilimab (BOT) and balstilimab (BAL). The most common side-effects, or treatment-related adverse events, were diarrhea and fatigue.
Justin Stebbing, Professor of Biomedical Sciences at Anglia Ruskin University (ARU) in Cambridge, England, and communicating author of the study, said: “These results are incredibly exciting. Colorectal or bowel cancer is one of the most common forms of cancer worldwide and this is the first time there has been convincing evidence that immunotherapy can work in all forms of colorectal tumours, so this is potentially game changing.
“This is now progressing into later phase clinical trials and we hope the FDA in the United States approve its use very soon. And because this is such an important area, affecting so many people, we hope authorities in the UK are also able to move quickly.”
Joint first author Dr Andrea Bullock, Assistant Professor in Medicine at Beth Israel Deaconess Medical Center, said: “This study sheds light on the potential of the BOT/BAL combination to treat microsatellite stable metastatic colorectal cancer, the most common form of colorectal cancer which has historically not responded to immunotherapy, and we hope our results will offer new hope for those diagnosed.”
Joint last author Dr Anthony El-Khoueiry, Associate Director of Clinical Research and Chief of Section of Developmental Therapeutics at the USC Norris Comprehensive Cancer Center, said: “This phase 1 study of botensilimab highlights its promising anti-tumour activity that encompasses immunologically cold tumours such as MSS colorectal cancer. The efficacy noted highlights the potential of botensilimab through its broader engagement of anti-tumour immunity.”

An international research team from Swansea University and UBC Okanagan (UBCO) has uncovered a new insight into human evolution by comparing humans’ hearts with those of other great apes.
Despite humans and non-human great apes having a common ancestor, the former has evolved larger brains and the ability to walk or run upright on two feet to travel long distances, likely to hunt.
Now, through a new comparative study of the form and function of the heart, published in Communications Biology, researchers believe they have discovered another piece of the evolutionary puzzle.
The team compared the human heart with those of our closest evolutionary relatives, including chimpanzees, orangutans, gorillas, and bonobos cared for at wildlife sanctuaries in Africa and zoos throughout Europe.
During these great apes’ routine veterinary procedures, the team used echocardiography — a cardiac ultrasound — to produce images of the left ventricle, the chamber of the heart that pumps blood around the body. Within the non-human great ape’s left ventricle, bundles of muscle extend into the chamber, called trabeculations.
Bryony Curry, a PhD student in the School of Health and Exercise Sciences at UBCO, said: “The left ventricle of a healthy human is relatively smooth, with predominantly compact muscle compared to the more trabeculated, mesh-like network in the non-human great apes.
“The difference is most pronounced at the apex, the bottom of the heart, where we found approximately four times the trabeculation in non-human great apes compared to humans.”
The team also measured the heart’s movement and velocities using speckle-tracking echocardiography, an imaging technique that traces the pattern of the cardiac muscle as it contracts and relaxes.

Bryony said: “We found that the degree of trabeculation in the heart was related to the amount of deformation, rotation and twist. In other words, in humans, who have the least trabeculation, we observed comparatively greater cardiac function. This finding supports our hypothesis that the human heart may have evolved away from the structure of other non-human great apes to meet the higher demands of humans’ unique ecological niche.”
A human’s larger brain and greater physical activity compared to other great apes can also be linked to higher metabolic demand, which requires a heart that can pump a greater volume of blood to the body.
Similarly, Higher blood flow contributes to humans’ ability to cool down, as blood vessels close to the skin dilate — observed as flushing of the skin — and lose heat to the air.
Dr Aimee Drane, Senior Lecturer from the Faculty of Medicine, Health & Life Sciences at Swansea University, said: “In evolutionary terms, our findings may suggest selective pressure was placed on the human heart to adapt to meet the demands of walking upright and managing thermal stress.
“What remains unclear is how the more trabeculated hearts of non-human great apes may be adaptive to their own ecological niches. Perhaps it’s a remaining structure of the ancestral heart, though, in nature, form most often serves a function.”
The research team is grateful to the staff and volunteers who care for the animals in the study, including the teams at Tchimpounga Wildlife Sanctuary (Congo), Chimfunshi Wildlife Sanctuary (Zambia), Tacugama Chimpanzee Sanctuary (Sierra Leone), Nyaru Menteng Orangutan Rescue and Rehabilitation Center (Borneo), the Zoological Society of London (UK), Paignton Zoo (UK), Bristol Zoo Gardens (UK), Burgers’ Zoo (Netherlands) and Wilhelma Zoo (Germany).

Fatty liver disease (steatotic liver disease, SLD for short) is increasingly causing failure of the liver as a vital organ. A team led by researchers from the Institute of Metabolic Physiology at Heinrich Heine University Düsseldorf (HHU) in collaboration with the German Diabetes Centre (DDZ) and other partners has now discovered that a saturated fatty acid in blood vessels leads to the production of the signalling molecule SEMA3A, which closes the ‘windows’ in the blood vessels. This hinders the transport of fat from the liver to the adipose tissue. In the journal Nature Cardiovascular Research, the researchers report that the windows open again and the fat in the liver is reduced when SEMA3A is inhibited.
In particular, ‘metabolic dysfunction-associated SLD’ (MASLD for short) can develop due to adverse lifestyle factors such as a high-energy diet and little exercise. It already affects around a third of all people worldwide. Initially, MASLD has no pathological effects, but it can develop into inflammation of the liver. In the long term, this may lead to liver cirrhosis, liver failure or even liver cancer. There is no substitute procedure that can take over the function of the liver in the long term, such as dialysis for kidney failure. Those affected are at high risk and may only be cured by a liver transplant.
In addition, people with MASLD have an increased risk of developing type 2 diabetes mellitus or dying from cardiovascular diseases. Obesity favours MASLD, but not all obese people are affected. And conversely, slim people can also develop the disease.
The molecular causes of the development of MASLD are not fully understood. A team of researchers from HHU, the DDZ (Leibniz Centre for Diabetes Research at HHU), Düsseldorf University Hospital (UKD) and Forschungszentrum Jülich (FZJ) have now discovered an important aspect that explains how MASLD develops.
The leading role is played by windows (Latin: fenestrae) in the endothelial cells of blood vessel, through which substances are exchanged between liver cells and blood. The liver uses these tiny windows to release excess fat particles into the adipose tissue via the bloodstream. The researchers discovered that these windows are closed by a mechanism in which the signalling molecule SEMA3A (semaphorin-3A) plays the central part. This molecule is produced in blood vessels when they are overly exposed to the saturated fatty acid “palmitic acid.”
Sydney Balkenhol from the Institute of Metabolic Physiology at HHU and the DDZ, first author of the study now published in Nature Cardiovascular Research, points to a discovery made by the team using scanning electron microscopy: The “windows” in the smallest blood vessels of the liver were also closed in mice with fatty liver and type 2 diabetes mellitus.
Dr Daniel Eberhard, the other first author, adds: “We were also able to reverse the effect. By inhibiting the signalling molecule, we could defat the liver and thus improve its function again.”
Corresponding author Dr Eckhard Lammert, Professor and Head of the Institute of Metabolic Physiology at HHU and the Institute of Vascular and Islet Cell Biology at the DDZ, hopes that the discoveries will also lead to a therapeutic approach for humans in the long term: “It may be possible to use the SEMA3A signalling molecule we identified to prevent MASLD and its consequences at an early stage. However, we first need to investigate the processes in humans in detail.”

Researchers at the University of Turku in Finland have found a new function for an existing protein. They discovered that TIMP-1, a protein traditionally known to prevent damage to the body’s cells and tissues, plays a critical role in the immune system’s defence against cancer. The findings of the study could improve the effectiveness of current cancer immunotherapies.
TIMP-1 protein is produced by dendritic cells, which are responsible for initiating immune responses and boosting the immune system’s ability to recognise and destroy cancer cells. The protein enhances antitumor immunity through self-stimulation and by activating surrounding immune cells. As a result, increasing TIMP-1 expression or targeting its negative regulators in tumours with deficient immune responses could potentially improve the effectiveness of current cancer immunotherapies.
“For patients deficient in TIMP-1 expression, our discovery helps create rational therapeutic innovations,” says Carlos Rogerio Figueiredo, Docent and InFLAMES researcher at the University of Turku.
According to Figueiredo, the new findings are also relevant for fighting infections by viruses and bacteria, as the process is part of a universal mechanism that fights microorganisms and cancer in a similar fashion.
The study used samples from the Finnish Auria Biobank for clinical-oriented discoveries, which were further validated with the latest biochemical and immunological tools to propose a new molecular view of how the body fights cancer. Figueiredo thanks the patients as well as Oncologist Maria Sundvall and Pathologist Eva-Maria Birkman from Turku University Hospital for their significant contributions to this project.
“The published research shows how the reverse translational method works in practice. Traditional translational research typically starts with basic laboratory discoveries, which are later tested on patients in clinical trials. The reverse translational approach, on the other hand, starts with real-world data from patient samples to guide focused laboratory studies, thereby enhancing the likelihood of success when applied to patients,” explains Figueiredo.
Figueiredo heads the Medical Immuno-Oncology Research Group (MIORG) at the Faculty of Medicine at the University of Turku, which is affiliated with the Turku Bioscience Centre and supported by the Research Council of Finland, InFLAMES Flagship, the Sigrid Juselius Foundation, and the Jane and Aatos Erkko Foundation.
The findings of the study were published in the journal Genes & Immunity, which is part of the Nature Portfolio series.
InFLAMES Flagship is a joint initiative of University of Turku and Åbo Akademi University, Finland. The goal of the Flagship is to integrate the immunological and immunology-related research activities to develop and exploit new diagnostic and therapeutic tools for personalised medicine. InFLAMES is part of Research Council of Finland’s Flagship Programme.

Periods of fasting reprogram the immune system’s natural killer cells to better fight cancer, according to a new study in mice from researchers at Memorial Sloan Kettering Cancer Center (MSK).
Fasting and other dietary regimens are increasingly being explored as ways to starve cancer cells of the nutrients they need to grow and to make cancer treatments more effective.
Now a team of researchers from MSK’s Sloan Kettering Institute and their collaborators have shown for the first time that fasting can reprogram the metabolism of natural killer cells, helping them to survive in the harsh environment in and around tumors, while also improving their cancer-fighting ability. The study, led by postdoctoral fellow Rebecca Delconte, PhD, was published June 14 in Immunity.
The findings could help explain one of the mechanisms by which fasting may help the body defend against cancer — along with more generally reducing fat and improving metabolism. And while more research is needed, the results also suggest fasting could be a strategy to improve immune responses to make immunotherapy more effective, the study authors note.
“Tumors are very hungry,” says immunologist Joseph Sun, PhD, the study’s senior author. “They take up essential nutrients, creating a hostile environment often rich in lipids that are detrimental to most immune cells. What we show here is that fasting reprograms these natural killer cells to better survive in this suppressive environment.”
What are Natural Killer Cells?
Natural killer cells, or NK cells for short, are a type of white blood cell that can kill abnormal or damaged cells, like cancer cells or cells infected with a virus. They get their name because they can destroy a threat without ever having encountered it before — unlike T cells, which require prior exposure to a specific enemy to mount a targeted response.

In general, the more NK cells that are present within a tumor, the better the prognosis is for the patient.
For the study, mice with cancer were denied food for 24 hours twice a week, and then allowed to eat freely in between fasts. This approach prevented the mice from losing weight overall, the authors note.
But these periods of fasting had a profound effect on NK cells.
Just as happens in humans, the mice saw a drop in their glucose levels and a rise in free fatty acids, which are lipids released by fat cells that can serve as an alternative energy source when other nutrients aren’t present, Dr. Delconte says.
“During each of these fasting cycles, NK cells learned to use these fatty acids as an alternative fuel source to glucose,” she says. “This really optimizes their anti-cancer response because the tumor microenvironment contains a high concentration of lipids, and now they’re able enter the tumor and survive better because of this metabolic training.”
Fasting Reprograms NK Cells
The fasting also led to a redistribution of NK cells within the body, the researchers observed.

Many of the NK cells traveled into the bone marrow, where, thanks to the fasting, they were exposed to high levels of a key signaling protein called Interleukin-12. This primed the NK cells to produce more Interferon-gamma — a cytokine that plays an important role in anti-tumor responses.
Meanwhile, NK cells in the spleen were undergoing a separate reprogramming, making them better at using lipids as a fuel source.
“With both of these mechanisms put together, we find that NK cells are pre-primed to produce more cytokines within the tumor,” Dr. Delconte says. “And with the metabolic reprogramming, they’re more able to survive in the tumor environment, and specialized to have improved anti-cancer properties.”
It’s unclear yet whether there are two separate populations of NK cells that get trained differently in different parts of the body, or whether the cells end up passing through both sites during their weeks-long life cycle.
“That’s the million-dollar question,” Dr. Sun says. “And one that we have only begun to answer using the cell-labeling techniques we used in this study.”
While human bone marrow samples weren’t studied as part of the project, the researchers note that blood samples from cancer patients show that fasting causes a reduction of freely circulating NK cells in people, just as they observed in mice.
Potential to Improve Cancer Treatments
There are several potential opportunities to advance the mouse-model research toward the clinic, the researchers say. First, clinical trials are already beginning to study the safety and effectiveness of fasting in combination with standard existing treatments. Another avenue would be to identify drugs that could target the underlying mechanisms without requiring patients to fast. Third, NK cells might be able to be put into a fasted state outside of the body, and then be administered to improve treatment effects.
At present, however, more clinical data is still needed about the effects of fasting for people with cancer, says Neil Iyengar, MD, an MSK breast medical oncologist and leading researcher on diet, metabolism, and cancer, who was not directly involved in the study.
“There are many different types of fasting, and some might be helpful while others might be harmful,” he says. “Patients should speak with their doctors about what’s safe and healthy for their individual situation.”

The amount of infectious H5N1 influenza viruses in raw milk rapidly declined with heat treatment in laboratory research conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. However, small, detectable amounts of infectious virus remained in raw milk samples with high virus levels when treated at 72 degrees Celsius (161.6 degrees Fahrenheit) for 15 seconds — one of the standard pasteurization methods used by the dairy industry. The authors of the study stress, however, that their findings reflect experimental conditions in a laboratory setting and are not identical to large-scale industrial pasteurization processes for raw milk. The findings were published today in the New England Journal of Medicine
In late March 2024, United States officials reported an outbreak of highly pathogenic avian influenza virus called HPAI H5N1 among dairy cows in Texas. To date, 95 cattle herds across 12 states have been affected, with three human infections detected in farm workers with conjunctivitis. Although the virus so far has shown no genetic evidence of acquiring the ability to spread from person to person, public health officials are closely monitoring the dairy cow situation as part of overarching pandemic preparedness efforts.
Given the limited data on the susceptibility of avian influenza viruses to pasteurization methods used by the dairy industry, scientists at NIAID’s Rocky Mountain Laboratories sought to quantify the stability of H5N1 virus in raw milk when tested at different time intervals at 63℃ (145.4 degrees Fahrenheit) and 72℃, the temperatures most common in commercial dairy pasteurization processes. The scientists isolated HPAI H5N1 from the lungs of a dead mountain lion in Montana. Then they mixed these viral isolates with raw, unpasteurized cow milk samples and heat-treated the milk at 63℃ and 72℃ for different periods of time. The samples were then cell-cultured and tested to determine if live virus remained and if so, how much.
They found that 63℃ caused a marked decrease (1010-fold) in infectious H5N1 virus levels within 2.5 minutes and note that standard bulk pasteurization of 30 minutes would eliminate infectious virus. At 72℃, they observed a decrease (104-fold) in infectious virus within five seconds, however, very small amounts of infectious virus were detected after up to 20 seconds of heat treatment in one out of three samples. “This finding indicates the potential for a relatively small but detectable quantity of H5N1 virus to remain infectious in milk after 15 seconds at 72℃ if the initial virus levels were sufficiently high,” the authors note.
The scientists stress that their measurements reflect experimental conditions, should be replicated with direct measurement of infected milk in commercial pasteurization equipment and should not be used to draw any conclusions about the safety of the U.S. milk supply. Additionally, a limitation of their study was the use of raw milk samples spiked with H5N1 virus, whereas raw milk from cows infected with H5N1 influenza may have a different composition or contain cell-associated virus that may impact heat effects. The authors conclude that although gastrointestinal infections with HPAI H5N1 virus have occurred in several species of mammals, it remains unknown whether ingesting live H5N1 in raw milk could cause illness in people.
To date, the U.S. Food and Drug Administration concludes that the totality of evidence continues to indicate that the commercial milk supply is safe. While laboratory benchtop studies provide important, useful information, there are limitations that challenge inferences to real-world commercial processing and pasteurization. The FDA conducted an initial survey of 297 retail dairy products collected at retail locations in 17 states and represented products produced at 132 processing locations in 38 states. All of the samples were found to be negative for viable virus. These results underscore the opportunity to conduct additional studies that closely replicate real-world conditions. FDA, in partnership with USDA, is conducting pasteurization validation studies — including the use of a homogenizer and continuous flow pasteurizer. Additional results will be made available as soon as they are available.

Scientists at St. Jude Children’s Research Hospital today announced a way to improve molecular scale distance measurements using single-molecule fluorescence resonance energy transfer (smFRET). smFRET quantifies the excitation and emission properties of chemicals called fluorophores.
When an excited electron in the fluorophore relaxes, it emits light after a delay, causing the molecule to glow (fluoresce). However, fluorophores don’t always fluoresce after excitation. Instead, through quantum mechanical processes related to the excited electron’s “spin” state, they can enter long-lived triplet dark states that do not fluoresce. This reduces the sensitivity and accuracy of smFRET measurements. By controlling the duration of dark states through “self-healing” technologies, St. Jude scientists now show that triplet dark states can be strongly mitigated. This advance significantly increases the method’s resolution to advance the field of molecular imaging. The findings were published today in Nature Methods.
smFRET captures fleeting molecular moments
Capturing the flap of a hummingbird’s wings requires specialized cameras with a high frame rate and lighting that avoids the blur of fast motion. Visualizing a hummingbird’s flight pales in comparison to the challenges of capturing the functions of biomolecules in our body. Biomolecules are smaller than the wavelength of light (on the order of one billionth of an inch), and their functions are tied to their motion, changing positions or shape (conformation) hundreds to thousands of times per second. Measuring these fleeting dynamics is vital to truly understand how molecules perform their functions, how these functions are perturbed in disease and how drug therapies modify their activities. smFRET, a molecular imaging technique, is a powerful way to directly visualize how biomolecules move in real-time and at the single-molecule scale.
At St. Jude, Scott Blanchard, PhD, Departments of Structural Biology and Chemical Biology & Therapeutics, is advancing the field of smFRET imaging. Efforts in the Blanchard lab, through the St. Jude Single-Molecule Imaging Center, have been critical to the design and development of fluorophores that enable measurements on the molecular scale.
“The most common and widely employed fluorescent molecules are generally not up to the task of quantifying events at the molecular scale. This led us to take on the challenge of synthesizing our own fluorophores,” Blanchard said. “In the process of doing so, we realized that the fundamental photophysics of fluorescence needed to be altered.”
To conduct smFRET experiments, researchers place fluorophores on two points of a biomolecule. When a laser is directed at the first of these fluorophores (the donor), an electron within it gains that energy, becoming excited. When the electron relaxes, this energy is transferred through space to the second fluorophore (the acceptor), but only if it is close to the donor. By recording and quantifying fluorescent bursts from both donor and acceptor fluorophores, distances can be measured on the order of one billionth of an inch. Each piece of information is vital to understanding biological function and malfunction. However, correct use of the technique requires careful navigation of the fundamental properties of fluorescence.

Electron spin flip locks in triplet state
The rules governing a fluorophore’s emission of light revolve around electron spin. When an excited electron relaxes, it should go back to its original state, maintaining its spin state or spin quantum number. This does not always happen, however.
“Every time an electron is excited, there’s a probability that it will lose memory of its spin and adopt an inverted spin state,” said Blanchard, corresponding author of the Nature Methods study. “While this process is relatively rare, with an approximate 1 in 100 probability, if it does change its spin state, then it ends up in this 100,000 times longer-lived triplet state that does not fluoresce. Consequently, the fluorophore becomes much dimmer than it otherwise could be.
“The field of fluorescence has been struggling with this for years,” Blanchard added. “In the context of FRET, we’ve noticed that triplet state accumulations change with illumination intensity and vary for different fluorophores.”
FRET requires the donor and the acceptor fluorophores to behave the same way. But, because the technique requires exciting one directly and not the other, when you turn up the laser, the triplet states of the donor and the acceptor become occupied at different rates.
“You end up with a sea-sickening process where the donor and the acceptor plateau at different levels, so they’re losing performance at different extents,” explained Blanchard. “Experimental readouts become varied, leading to reductions in the quality and reliability of the imaging data. This fundamentally restricts both the spatial and temporal resolution limits of smFRET measurements.”
A key goal of fluorophore engineering studies is, therefore, to reduce the lifetime of triplet states to the extent that is possible. This is the foundational goal of ‘self-healing’ technologies.

“To ensure accurate distance measurements in smFRET data, the field currently relies on calibration steps that do not explicitly consider triplet states,” explained co-first author Zeliha Kilic, PhD, St. Jude Department of Structural Biology. “Self-healing technologies move the field closer to optimal conditions where triplet states are absent, ensuring that the calibration steps employed yield more accurate results and thus distance measurements.”
Self-healing fluorophores guide the way
Chemicals called triplet state quenchers, such as cyclooctatetraene, counteract this phenomenon but also tend to gum up the works. “Cyclooctatetraene is greasy, exhibits varied and low solubilities, and is challenging to control,” said Blanchard.
Previous publications from Blanchard’s team reported the development of fluorophores with cyclooctatetraene directly attached. This approach solved the solubility issue and created “self-healing” fluorophores in which triplet state occupation was reduced by up to 1000-fold. In the new study, the researchers demonstrated that using self-healing fluorophores as donors and acceptors in smFRET experiments improves data quality and reliability and prevents loss in imaging quality as laser intensity increases. These improvements push forward the frontiers of smFRET, and self-healing fluorophore technologies are finding increasingly diverse applications worldwide.
“The enhanced brightness and photostability of self-healing fluorophores make it possible to improve the spatiotemporal resolution of smFRET imaging dramatically,” said co-first author Avik Pati, PhD, formerly of St. Jude Department of Structural Biology, now of Birla Institute of Technology and Science. “We can now robustly quantify nanometer-scale conformational dynamics within single biomolecules at sub-milliseconds and at physiological oxygen concentrations.”
Blanchard is confident these findings will help St. Jude researchers and the broader scientific community. “Pushing the frontiers of imaging innovations at St. Jude is part of the institution’s strategic plan, and we are confident that self-healing fluorophores will play an important role in meeting our goals,” he said. “Moreover, many are likely to benefit from these advancements as the self-healing approach has shown potential to improve most fluorescence applications.”

A widely available drug helps prevent upper gastrointestinal bleeding in critically ill adults on a breathing machine, according to the results of a global study and meta-analysis led by researchers at McMaster University.
The research, published on June 14, 2024 in The New England Journal of Medicine and NEJM Evidence, investigated the effect of the gastric acid suppressant pantoprazole, which is primarily used to treat heartburn caused by gastroesophageal reflux disease (GERD).
Patients in the intensive care unit (ICU) who need a breathing machine (mechanical ventilator) also receive pantoprazole to prevent upper gastrointestinal bleeding, caused by stress-induced ulcers in the stomach. Concerns emerged about whether this complication of critical illness had disappeared over the years, and about side effects of pantoprazole, including increased risk of death in the sickest patients. The research provides critical care teams with certainty about whether the medications should be used in practice.
“This is the largest randomized trial on this topic in the world, led by Canada. Physicians, nurses, and pharmacists working in the ICU setting will use this information in practice right away, and the trial results and the updated meta-analysis will be incorporated into international practice guidelines,” said lead author and principal investigator Deborah Cook, a professor in the Department of Medicine at McMaster.
Global randomized control trial
The Reevaluating the Inhibition of Stress Erosions (REVISE) Trial was a randomized control trial that compared the effect of pantoprazole to placebo in critically ill adults on a breathing machine. The trial was run in 68 centres in eight countries and over 4,800 patients underwent randomization. Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo but not in a lower risk of death.
Clinically important upper gastrointestinal bleeding occurred in 25 of 2,417 patients (one per cent) receiving pantoprazole and in 84 of 2404 patients (nearly four per cent) receiving placebo. At 90 days, death was reported in 696 of 2390 patients (29 per cent) in the pantoprazole group and in 734 of 2379 patients (30 per cent) in the placebo group.

Updated systematic review
Researchers conducted a meta-analysis of 12 randomized trials of proton-pump inhibitors for GI bleeding prevention in 10,000 critically ill patients to summarize the current evidence on the outcomes of gastrointestinal bleeding, mortality, pneumonia and C. difficile infection.
The medications were associated with a reduced incidence of clinically important upper gastrointestinal bleeding and may have little or no effect on mortality. The evidence also showed the medications may have no effect on pneumonia and little or no effect on C. difficile infection.
The research was funded by the Canadian Institutes for Health Research, the Accelerating Clinical Trials Fund, Physicians Services Incorporated of Ontario, Hamilton Association of Health Sciences Organization, and the National Health Medical Research Council of Australia.

A new emotion has taken over Riley’s teenage mind. And she has lessons for us all.At the end of “Inside Out,” the 2015 Pixar movie about the emotional life of a girl named Riley, a new button appears on the console used to control Riley’s mood. It’s emblazoned with one word: Puberty.Joy, one of the main characters who embodies Riley’s emotions, shrugs it off.“Things couldn’t be better!” Joy says. “After all, Riley’s 12 now. What could happen?”The answer has finally arrived, nearly a decade later, in the sequel “Inside Out 2.” Riley is now a teenager attending a three-day hockey camp as new, more complex feelings take root in her mind.There’s Embarrassment, a lumbering fellow who unsuccessfully attempts to hide in his hoodie; the noodle-like Ennui, who lounges listlessly on a couch; and Envy, with her wide, longing eyes.But it is Anxiety who takes center stage, entering Riley’s mind with literal baggage (no less than six suitcases).“OK, how can I help?” she asks. “I can take notes, get coffee, manage your calendar, walk your dog, carry your things — watch you sleep?”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

In a new book, Dr. Anthony S. Fauci recounts a career advising seven presidents. The chapter about Donald J. Trump is titled “He Loves Me, He Loves Me Not.”Three months into the coronavirus pandemic, Dr. Anthony S. Fauci was at home in northwest Washington when he answered his cellphone to President Donald J. Trump screaming at him in an expletive-laden rant. He had incurred the president’s wrath by remarking that the vaccines under development might not provide long-lasting immunity.That was the day, June 3, 2020, “that I first experienced the brunt of the president’s rage,” Dr. Fauci writes in his forthcoming autobiography.Dr. Fauci has long been circumspect in describing his feelings toward Mr. Trump. But in the book, “On Call: A Doctor’s Journey in Public Service,” he writes with candor about their relationship, which he describes as “complicated.”In a chapter entitled “He Loves Me, He Loves Me Not,” Dr. Fauci described how Mr. Trump repeatedly told him he “loved” him while at the same time excoriating him with tirades flecked with four-letter words.“The president was irate, saying that I could not keep doing this to him,” Dr. Fauci wrote. “He said he loved me, but the country was in trouble, and I was making it worse. He added that the stock market went up only 600 points in response to the positive Phase 1 vaccine news, and it should have gone up 1,000 points, and so I cost the country ‘one trillion dollars.’” (The president added an expletive.)“I have a pretty thick skin,” Dr. Fauci added, “but getting yelled at by the president of the United States, no matter how much he tells you that he loves you, is not fun.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.