Tag: 17/7/23

Categories : CancerTags :

Scientists Find a Protein That Keeps Melanoma Hidden from the Immune System

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3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

New research has helped explain how melanoma evades the immune system and may guide the discovery of future therapies for the disease. The study found that a protein known to be active in immune cells is also active inside melanoma cells, helping promote tumour growth. The findings, published in the journal Science Advances, suggest that targeting this protein with new drugs may deliver a powerful double hit to melanoma tumours.

“The immune system’s control of a tumour is influenced by both internal factors within tumour cells, as well as factors from the tumour’s surroundings,” says first author Hyungsoo Kim, PhD, a research assistant professor at Sanford Burnham Prebys in the lab of senior author Ze’ev Ronai, PhD. “We found that the protein we’re studying is involved in both, which makes it an ideal target for new cancer therapies.”

“Immunotherapy is the first-line therapy for several cancers now, but the success of immunotherapy is limited because many cancers either don’t respond to it or become resistant over time,” says Kim. “An important goal remains to improve the effectiveness of immunotherapy.”

To find ways to boost immunotherapy in melanoma, the research team analysed data from patient tumours to identify genes that may coincide with patients’ responsiveness to immunotherapy. This led to the identification of a protein that helps tumours evade the immune system – called NR2F6 – which was found not only in tumour cells, but also in the surrounding noncancerous cells.

“Often we find that a protein has the opposite effect outside of tumours compared to what it does within a tumour, which is less effective for therapy,” says Kim. “In the case of NR2F6, we found that it elicits the same change in the tumour and in its surrounding tissues, pointing to a synergistic effect. This means that treatments that block this protein’s activity could be twice as effective.”

In a mouse model, the researchers then deleted the NR2F6 protein in both melanoma tumours and in the tumours’ environment. This inhibited melanoma growth more strongly, compared to when this effect occurs in either the tumour or its microenvironment alone. The cancer’s response to immunotherapy was also enhanced upon loss of NR2F6 in both tumours and their microenvironment.

“This tells us that NR2F6 helps melanoma evade the immune system, and without it, the immune system can more readily suppress tumour growth,” adds Kim.

To help advance their discovery further, the team is working with the Institute’s Conrad Prebys Center for Chemical Genomics to identify new drugs that can target NR2F6.

“Discovering drugs that can target this protein are expected to offer a new way to treat melanomas, and possibly other tumours, that would otherwise resist immunotherapy,” says Kim.

Source: Sanford Burnham Prebys

Categories : Obstetrics & Gynaecology PaediatricsTags :

Multidisciplinary Approach Reduced Hypothermia in NICU Babies During and After Surgery

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Photo by Hush Naidoo on Unsplash

After implementation of a multidisciplinary quality improvement project, the percentage of infants from the neonatal intensive care unit (NICU) experiencing hypothermia upon operating room (OR) arrival and at any point during the operation decreased from 48.7% to 6.4% and 67.5% to 37.4%, respectively. Conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago, the successful project and was featured in the journal Pediatric Quality and Safety.

About one-third of infants admitted to children’s hospitals’ NICUs require surgery and are at increased risk for intraoperative hypothermia due to environmental heat loss, anaesthesia, and inconsistent temperature monitoring. Hypothermic infants are at risk for infection, excessive bleeding, increased oxygen consumption, the need for cardiorespiratory support, and mortality.

Upon return to the NICU, the percentage of infants experiencing postoperative hypothermia decreased from 5.8% to 2.1% while postoperative hyperthermia increased from 0.8% to 2.6%.

“Intraoperative hypothermia is more prevalent than postoperative hypothermia, yet the problem appears to be recognized less. Several improvement projects have addressed postoperative hypothermia, however, few have focused on reducing intraoperative hypothermia,” said senior author Gustave Falciglia, MD, MSCI, MSHQPS, neonatologist at Lurie Children’s. “The strengths of our project were the large cohort of infants and the use of continuous, secure and automated data to ensure normal temperature for infants before, during and after an operation. Using our current approach, however, further decreasing intraoperative and postoperative hypothermia may not be possible without further increasing postoperative hyperthermia.”

Dr Falciglia and colleagues from Lurie Children’s Center for Quality and Safety, anaesthesiology, NICU and OR nursing, surgery, neonatology and Data Analytics and Reporting succeeded in reducing rates of intraoperative hypothermia by standardising temperature monitoring, the transport process to the OR and intraoperative warming.

“In this project, we used improvement science methodology to understand the barriers to maintaining normal temperature in NICU infants before, during and after surgery, and then to design and implement solutions,” said lead author Abbey Studer from the Center for Quality and Safety at Lurie Children’s. “We found variation in processes that contributed to intraoperative hypothermia, so we focused on standardizing temperature monitoring and thermal support during the infant’s transport and operation. Automated monitoring using a preoperatively placed continuous temperature probe enhanced providers’ situational awareness of infant temperature and guided clinical adjustments.”

For this improvement project, the hospital’s Center for Quality and Safety coordinated care and resources between multiple departments. It achieved consensus and buy-in from providers despite competing factors such as perspiring surgeons and busy anaesthesia providers transporting all infants to the OR. It identified key participants who were vested in revising processes and facilitated adoption with their colleagues, following up on missed opportunities and gaps in the processes identified through observation and surveys. The centre provided data analysts who worked iteratively with providers to generate valid, actionable, and real-time data.

“Although medicine prizes specialisation, our success relied upon individuals with various talents sharing their skills and knowledge,” said Dr Falciglia. “Working together we can continue to improve the care of infants in the NICU who need surgery.”

Source: Ann & Robert H. Lurie Children’s Hospital of Chicago

Categories : Lab Tests and Imaging Obstetrics & GynaecologyTags : 1 Comment

Researchers Discover a Lipid Biomarker that can Identify Preeclampsia Risk

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Photo by Shvets Production on Pexels

University of Virginia School of Medicine researchers have discovered a lipid biomarker to identify pregnant women at risk of preeclampsia, complications from which are the second-leading cause of maternal death around the world. Their findings are published in the Journal of Lipid Research.

The UVA scientists, led by Charles E. Chalfant, PhD, say that their finding opens the door to simple blood tests to screen patients. Further, the approach worked regardless of whether the women were on aspirin therapy, which is commonly prescribed to women thought to be at risk.

“Clinicians have been seeking simple tests to predict risk of preeclampsia before symptoms appear. Although alterations in some blood lipid levels have been known to occur in preeclampsia, they have not been endorsed as useful biomarkers. Our study presents the first comprehensive analysis of lipid species, yielding a distinctive profile associated with the development of preeclampsia,” said Chalfant. “The lipid ‘signature’ we described could significantly improve the ability to identify patients needing preventative treatment, like aspirin, or more careful monitoring for early signs of disease so that treatment could be initiated in a timely fashion.”

Preeclampsia affects up to 7% of all pregnancies. Symptoms typically appear after 20 weeks and include high blood pressure, kidney problems and abnormalties in blood clotting. The condition is associated with dangerous complications such as kidney and liver dysfunction and seizures, as well as a lifelong increased risk of heart disease for the mothers. An estimated 70 000 women around the world die from preeclampsia and its complications each year.

Doctors commonly recommend low-dose aspirin for at-risk women, but it works for only about half of patients, and it needs to be started within the first 16 weeks of pregnancy – well before symptoms appear. That makes it all the more important to identify women at risk early on, and to better understand preeclampsia in general.

Chalfant and his team wanted to find ‘biomarkers’ in the blood of pregnant women that could reveal their risk of developing preeclampsia. They examined blood plasma samples collected from 57 women in their first 24 weeks of pregnancy, then looked at whether the women went on to develop preeclampsia. The researchers found significant differences in ‘bioactive’ lipids in the blood of women who developed preeclampsia and those who did not.

This, the researchers say, should allow doctors to stratify women’s risk of developing preeclampsia by measuring lipid changes in their blood. The changes represent an important ‘lipid fingerprint’, the scientists say, that could be a useful tool for identifying, preventing and better treating preeclampsia.

“The application of our comprehensive lipid profiling method to routine obstetrical care could significantly reduce maternal and neonatal morbidity and mortality,” Chalfant said. “It represents an example of how personalised medicine could address a significant public health challenge.”

Source: University of Virginia Health System

Categories : Mental HealthTags :

Generic Ketamine Performs Strongly for Treatment-resistant Depression

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Photo by Sydney Sims on Unsplash

A low-cost version of ketamine to treat severe depression has performed strongly in a placebo-controlled double-blind trial. Results published in the British Journal of Psychiatry showed that more than one in five participants achieved total remission from their symptoms after a month of bi-weekly injections, while a third had their symptoms improve by at least 50%.

“For people with treatment-resistant depression – so those who have not benefitted from different modes of talk-therapy, commonly prescribed antidepressants, or electroconvulsive therapy – 20 per cent remission is actually quite good,” lead researcher Professor Colleen Loo says.

“We found that in this trial, ketamine was clearly better than the placebo – with 20 per cent reporting they no longer had clinical depression compared with only 2 per cent in the placebo group. This is a huge and very obvious difference and brings definitive evidence to the field which only had past smaller trials that compared ketamine with placebo.”

How the trial worked

The researchers, led by UNSW Sydney and the affiliated Black Dog Institute, recruited 179 people with treatment-resistant depression. All were given an injection of either a generic form of ketamine that is already widely available in Australia as a drug for anaesthesia and sedation – or placebo. Participants received two injections a week in a clinic where they were monitored for around two hours while acute dissociative and sedative effects wore off, usually within the first hour. The treatment ran for a month and participants were asked to assess their mood at the end of the trial and one month later.

In this double-blind trial, a placebo was chosen that also causes sedation, to improve treatment masking. Midazolam is a sedative normally administered before a general anaesthetic, while in many previous studies the placebo was saline.

“Because there are no subjective effects from the saline, in previous studies it became obvious which people were receiving the ketamine and which people received placebo,” Prof Loo says.

“In using midazolam – which is not a treatment for depression, but does make you feel a bit woozy and out of it – you have much less chance of knowing whether you have received ketamine, which has similar acute effects.”

Other features of the recent trial that set it apart from past studies included accepting people into the trial who had previously received electroconvulsive therapy (ECT).

“People are recommended ECT treatment for their depression when all other treatments have been ineffective,” Prof. Loo says.

“Most studies exclude people who have had ECT because it is very hard for a new treatment to work where ECT has not.”

Another difference about this trial was that the drug was delivered subcutaneously (injected into the skin) rather than by drip, thus greatly reducing time and medical complexity. The study is also the largest in the world to date that compares generic ketamine with placebo in treating severe depression.

Much more affordable

Apart from the positive results, one of the standout benefits of using generic ketamine for treatment-resistant depression is that it is much cheaper than the patented S-ketamine nasal spray currently in use in Australia. Where S-ketamine costs about AUS$800 (R9 600) per dose, the generic ketamine is a mere fraction of that, costing as little as AUS$5 (R60), depending on the supplier and whether the hospital buys it wholesale. On top of the cost for the drug, patients need to pay for the medical care they receive to ensure their experience is safe – which at Black Dog Institute clinics, comes to AUS$350 (R4200) per session.

“With the S-ketamine nasal spray, you are out of pocket by about AUS$1200 for every treatment by the time you pay for the drug and the procedure, whereas for generic ketamine, you’re paying around AUS$300-350 for the treatment including the drug cost,” Prof Loo says.

She adds that for both S-ketamine and generic ketamine treatments, the positive effects often wear off after a few days to weeks, so ongoing treatment may be required, depending on someone’s clinical situation. But the prohibitive costs of the drug and procedure make this an unsustainable proposition for most.

The researchers will next be looking at larger trials of generic ketamine over longer periods, and refining the safety monitoring of treatment.

Source: University of New South Wales

Categories : Hospitals Surgeries & ProceduresTags :

Cancellation of Operations at the Charlotte Maxeke Johannesburg Academic Hospital

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The Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) would like to dismiss the misleading information shared by Mr Jack Bloom regarding cancelled operations.

CMJAH would like to put it on record that there were no “more than 50 elective cases cancelled due to the cold weather conditions”. The statement by Mr Bloom creates the impression that all elective cases were cancelled, which is not true.

There were 53 operations scheduled for Monday, 10 July 2023, and 26 cases were done, while only 15 were cancelled due to low temperatures at theatres and 12 were cancelled for reasons not related to low temperatures.

Out of the 15 cancelled cases, 3 were for Thoracic, 6 were for Trauma Orthopaedic, 2 were for Paeds Orthopaedic, 1 was for Paeds plastics, and 3 were for Ear, Nose, & Throat.

The problem of temperature control has been a challenge for the facility for years, but it became worse in the last two years due to the copper theft which took place during the period when the facility was evacuated for months after the fire incident. This affected the central heating system of the facility, which regulates the level of acceptable temperatures in the entire hospital, but mostly in the theatres.

To remedy the situation, the process of installing Schedule 40 pipes, which are less susceptible to theft as they do not have an attractive market value as copper does, has started. During the installation process, the theatres and intensive care units (ICU) were prioritised. From the date of appointment, 28 June 2023, to date, the contractor has completed the installation of schedule 40 pipes for Blocks 2, 3 and 4. The installation process at Block 5 has already started and the work is progressing well, ahead of schedule.

The water system is currently running, with close monitoring, at all three blocks where the schedule 40 pipes were installed to check for any possible leaks as the system has not been running for the past two years.

The facility would like to apologise to the public for any inconvenience this might have caused. The installation of the schedule 40 pipes is a necessary project that would address the issue of copper theft and the central heating system.

The facility would further like to assure the public that this matter is getting the urgency it deserves, and cancelled cases are being attended to.

News release issued by the Charlotte Maxeke Johannesburg Academic Hospital

Categories : Cardiovascular DiseaseTags :

Cardiac Arrest Survivors have Better Outcomes if Cerebrovascular Regulation Kicks in

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Source: CC0

A study of out-of-hospital cardiac arrest patients has shown that they have better neurological outcomes if a protective cerebrovascular regulation system reasserts itself. The research, published in the Journal of Cerebral Blood Flow and Metabolism, shows that this information can be used to assign more intensive rehabilitation, and also can be used to develop new interventions to improve cerebral perfusion.

Despite advances in treatment for out-of-hospital cardiopulmonary arrest and efforts to improve outcomes, many patients still suffer neurological sequelae (hypoxic-ischaemic brain injury, HIBI) even after return of spontaneous circulation. It is known that if brain function is maintained normally, there is a mechanism, cerebrovascular autoregulation (CVAR), that tries to maintain cerebral blood flow at a constant level even with changes in systemic blood pressure, but until now, it was unclear whether such a reaction occurs in the brain after resuscitation. Cerebral regional oxygen saturation (crSO2), a measure of oxygen supply and demand balance in the brain, is affected by blood pressure, and we focused on a method to evaluate the presence or absence of CVAR using this correlation. The researchers used this correlation to evaluate the presence or absence of CVAR in the post-resuscitated brain and assessed its relationship to life expectancy.

In this study, the research group analysed 100 patients with out-of-hospital cardiac arrest who were transported to the trauma and acute critical care centre of the Osaka University Graduate School of Medicine. CVAR was determined by calculating the moving Pearson correlation coefficient and by continuously monitoring crSO2 and mean blood pressure for 96 hours after return of spontaneous circulation. Assuming undetected CVAR time as a bad exposure for the organism (time-dependent covariate), the researchers evaluated the association of life prognosis using Cox proportional hazards model. CVAR was detected in all 24 patients with good neuroprognosis (Cerebral Performance Scale5: CPC 1-2) out of 100 analysed subjects and in 65 (88%) of 76 patients with poor neuroprognosis (CPC 3-5). The analysis using the Cox proportional hazards model showed that the survival rate decreased significantly as the undetected time of CVAR increased.

The results of this study have two major implications. First, the ability to identify subgroups with high mortality from early post-resuscitation clinical data can help identify populations that should receive enhanced therapeutic intervention. In addition, it may help to avoid early withdrawal of treatment from those who may recover. Secondly, we believe that intensive therapeutic management that maintains proper cerebral perfusion suggests improved life outcomes, and that developing a systemic management approach based on cerebral perfusion may be a breakthrough in reducing post-resuscitation neurological sequelae.

Source: EurekAlert!