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How has Covid-19 affected urology? Top doctors explain

Healthcare experts and doctors answer queries around the impact of the pandemic on urology, the latest developments in this branch of medicine as well as risks and challenges of a kidney transplant.

Shalini Bhardwaj

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Top healthcare experts discuss the roadblocks and latest advancements in urology, urology cancer and more. Dr Anup Kumar, HoD of urology, Safdarjung Hospital, Dr Anand Kumar, head of urology and kidney transplant division, Max Hospital, Dr Rajiv Sood, dean of PGIMER, RML Hospital and chairman of Indian School of Urology, and Dr Amlesh Seth, HoD of urology at AIIMs, put forth their views. Excerpts:

Q. What are the challenges involved in kidney transplant?

Dr Anand Kumar: Kidney transplant involves two people, one person who is going to get the kidney and the other who will donate it. This is a unique situation in the medical field as it is the only operation in which a healthy person is undergoing an operation to give one of the organs or part of the organ to someone else to live. Somebody who has just died has agreed to donate his organ then his organ can also be given to others. It is a big challenge. Nowadays there are nuclear families, suppose someone has kidney disease, previously in the family there used to be at least three to four children but now usually there are only two children. If they are not matching there is a problem and if one has gone outside the country or some other thing then there is a problem in finding a particular donor for kidney transplantation. Apart from this, it is also a financially and emotionally draining situation. Your treatment is expensive, it goes throughout life and the initial preparation is also required as the patient undergoes dialysis and a lot of tests. We have to see if the patient is fit or not to undergo the transplant. His donor also has to go through a lot of tests. All these issues are there and then we go for the transplantation. Sometimes no family member is fit to donate even if they want to. Only a healthy person can donate, suppose the donor has got some liver disease, both his kidneys are not good, he has diabetes, has major pressure issues or heart disease so even if he is willing to donate and wants to save the other person, he still can’t do that. We can’t risk his life while taking out his kidney in donation as our job is to make sure that the person who is donating should remain healthy, he should not suffer and the one who got the kidney should also do well. 

Q. How much risk is involved in a kidney transplant?

Dr Anand Kumar: Kidney transplant nowadays has become a very routine procedure. Firstly, we will take the kidney donation, it is done electroscopically. The patient is admitted for three to four days. The procedure usually takes one to two hours, the next day the patient needs only a small procedure to take the kidney out, the next step is walking around, moving around, and on the third-fourth day, the patient is discharged. Within two to three weeks, he is fit and fine after which he doesn’t need to take any medication or precaution. He can do anything except two things, he cannot join the army and police force. Besides that, he can go hiking, cycling, and produce children so the donor has no risk. The operation has become very safe but in one out of 3000 cases there can be some complication.

Q. Do you think we need awareness as people still feel that they should not donate a kidney, especially family members and there is some hesitation?

Dr Anand Kumar: Yes, it needs awareness and we salute those who donate their kidney, it is not an easy decision. If I ask somebody to give Rs 100 he would think a few times before giving it. If I ask somebody to donate his blood, it would not be a problem as when you give the blood nothing happens, within a few hours your blood is replaced. Still, people are hesitating to donate. Asking somebody to undergo some major operation to donate their kidney is not at all that simple but still, people do it. It takes a lot of courage and self-determination to donate and help somebody. They are doing a very altruistic act to save somebody’s life; it is not an easy decision and takes time. We counsel them, give them literature to read and build their confidence. A lot of people come forward so I salute them that they have done a great job, and saved somebody’s life. It needs awareness that donation is simple and safe, there is no disfiguration of the abdomen and very soon you will be back to your work and can do anything. Another thing that needs a lot of awareness is cadaver donation. Many people are dying because of roadside accidents, brain haemorrhage, a clot in the brain, and sudden cardiac death so when they are in the hospital their family agrees to donate their organs. One person can save many people’s lives, you can donate eyes, liver, lungs, heart, kidneys, pancreases, small bowel, cartilage and other organs. One person can save seven lives when the family allows it. There is the system, law, many foundations, and NOTO (National Organ Transplant Organisation), so there’s nothing to fear about. The family just has to give consent. 

Q. What is urology cancer? Does a urologist treat cancer?

Dr Anup Kumar: Yes, urology cancer is treated by a urologist, we call them urooncologist. It is a separate speciality these days and that includes cancer, soft kidney, and bladder, etc. All these cancers have various presentations, various stages and a lot of advances have taken place in the field of urology. Earlier it used to be open surgeries for all cancers. Then there are laparoscopic surgeries, minimally invasive surgeries, but then laparoscopic surgeries had some disadvantages and limitations especially in certain challenging cases. Then came the era of robotics and this era came in the last 20 years, we are seeing its benefits in terms of least mobility to the patients and decrease in mortality. Patients don’t have long insurgents which we give in the open surgery so there is less pain, less blood loss, lesser need for the blood transfusion and the patient recovers faster. In terms of the outcome, we recover cancer totally, not leaving cancer behind. That is known as R0 resection efficacy is also increased, enhanced and is equivalent to open surgery. Functional outcomes and quantity of life outcomes are very important in today’s era. The patients are aware of these things and demand a good quality of life which we can give them. Talking about radical prostatectomy, earlier the patient feared that they would leak the urine continuously after surgery and had many other fears. Nowadays with the robotic approach, we can not only give them excellent continence and many of the patients are immediately continent after surgery and almost 80-90% will become continent in three months which is a very good number. We can also preserve the nerves which give normal life after surgery.

Q. How Artificial intelligence (AI) is useful in urology?

Dr Anup Kumar: AI is a big field that is going to be there in the robotic field. Right now, we are not using AI, but we have the robots which are coming, these robots don’t have haptic feedback, i.e. no tactile sensation which we have in open or lab. In AI we are going to have haptic feedback again and that will improve the outcome of the surgery. AI is the future of all these technologies, especially robotics.

Q. What are the latest developments in urology?

Dr Amlesh Seth: There are so many developments that it is very difficult to talk about one or two. Dr Anup has already talked about robotics and AI. In urological cancer, gene therapy is coming up and targeted therapy has already been there and there are multi-mortality treatments for urological cancer which becomes more and more streamlined. The cure rates for testicular cancer is 99% and good longevity is provided in patients with prostate cancer, kidney cancer, and bladder cancer. In bladder cancer, a new bladder formation has been going on and in about two to three decades, if the urinary bladder is taken out then the new bladder can be formed from the intestine. The patients avoid it almost as if the patient has an inactive bladder. People fear the bladder being removed. 

Q. How Covid-19 has affected urology?

Dr Rajiv Sood: In urology we have all kinds of exposures to the health workers which are there in any other discipline also but the special thing is that in urology we are having a lot of diseases which are very common like UTI, cancer, the kidney stones, or any disease ureteric disease for the elderly where the comorbidities are also there. We have elderly patients, a patient profile that should not be exposed to the Covid pandemic and also they are pre-disposed because of the comorbidities occurring side by side. Now in urology heavy rush is managed by using the face screen and a screen between patients and doctors, besides sanitising and keeping distance. Firstly, the last March onwards tele-counselling has been legalised and if you see a patient you are already examined for the next six months. You can do tele-counselling through any social platform or any dedicated platform. Secondly, we have modified certain guidelines in urology, all OPD indoor, OT protocols and cancer guidelines are modified. In prostate cancer, everybody should treat it once we recognise it is cancer. Unless it is very slow-growing, safe, or low risk but when there is a chance we have to decide whether we are going for a biopsy or not. We have to decide their imaging, not the therapy protocols as we have modified the radiotherapy i.e. the radiation protocols. Also initially there were a lot of apprehends for the laparoscopic surgeries as aerosol spread were also feared. Now because of certain precautions and special protocols we can perform those also. Urological surgeries sometimes are very small as they last for just cystoscopy which is a very short duration and sometimes they are very time consuming and may last for seven to nine hours. We know that in Covid for the long procedure the exposure is long and the viral dose is also high so we have to decide whether we are going for the short procedure, long procedure, short exposure, long exposure and how many times we are calling the patient if we are giving chemotherapy. As Dr Amlesh was saying, that there is target therapy also or the pills for some alternate treatment. Maybe the second line hormones treatments for cancer there are pills. We were preferring that we do not hospitalise the patients and give more of the outdoor treatments and home cure whenever it is possible. What is the effect of Covid on the pre-existing renal or the urological conditions and condition caused by covid? That is also very important as we have identified a lot many biomarkers. If biomarkers are present in the organ we know that these organs are expressed to more damage. Now there are ACE2 receptors. ACE is the angiotensin-converting enzyme that is very important and is present in different organs like the entry point of the nose, eyes, and intestine but in the urological tissues like the kidney, especially in the proximal tubules, they are present. This is the entry point for coronavirus and once they enter through this they start replicating. Therefore, urologists become important because in no previous commodity also patients are exposed to acute kidney injuries which are very serious. If the pulmonary lungs are affected they go high, their morbidity, motility also go high. So maximum acute kidney injuries are occurring in ICUs indoors compared to the outdoor or homecare covid patients and this may have long term consequences. There are certain procedures like kidney stone and we don›t have a table to accommodate them as a lot of OT’s were shut and there are a lot of backlog patients suffering whom we have to take care of. In cancer, radiations like you give the doses you go for hypofractionation means you give small doses. Also in surgeries, we have to decide whether we can postpone the surgery and also there is an effect on fertility because of the inflammatory reactions of the Leydig cells which are important in the spermiogenesis and also because of direct inflammation which is the main problem in covid infection and testis gets damage so fertility gets affected. It has been found that the fertility rates go down, not only that there is another angle another at the end of the spectrum—i.e. because of the undesired conceptions you are not able to go for MTP the Medical Termination of Pregnancy. Due to the different work from home and social conditions in some advanced countries, educated countries, there had been a decrease in the population due to the involvement of mental health also.

Q. Has it affected mental health also?

Dr Rajiv Sood: Yes, it is connected with the population also. In India, it was found that a 3.1% increase in the birth rate and that is called the baby boom. The population is going down and going up in many countries, directly sexual organs and genital organs are getting affected.

Q. Why is infertility increasing in men, especially in the younger generation?

Dr Anup Kumar: The causes for increasing infertility are increased use of alcohol and tobacco in the younger generation. We are also seeing an increase in the trend of diabetes, type 1 diabetes, and hypertension in the younger population. This is all because these are lifestyle diseases and the younger generation do not take healthy food, do not exercise and are having obesity. Just like in the USA an obesity pandemic going on, we can see the number of obese patients in India is also increasing. Other than that, there are some other idiopathic genetic factors also which are increasing infertility cases in India. Therefore, it is very important to have a healthy lifestyle, do not take alcohol and tobacco, workout for at least 30 minutes per day, do not take frozen meat as the meat contains very toxic chemicals which can impair your sperm production, avoid extreme heat exposures as it can lead to the failure of the spermatogenesis. Also, certain chemotherapist drugs can directly affect sperm production. There is a production decrease after the drugs and these patients can preserve the sperms before starting chemotherapy.

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STUDY ASSERTS BLOOD ENZYME ACTIVITY LEVEL MAY INDICATE WHICH BREAST CANCERS ARE GROWING SLOW

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Patients with metastatic hormone receptor-positive breast cancer who have low activity levels of the enzyme sTK1 in their blood serum at the start of anti-estrogen treatment live longer and go longer without their disease progressing than patients with high levels, according to a recent study by SWOG (the Southwest Oncology Group) Cancer Research Network.

The findings of the study were published in the journal ‘Clinical Cancer Research’. The results suggest that patients with low sTK1 activity levels have a slow-growing disease that can be controlled initially with single-drug endocrine therapy for a prolonged period.

It remains to be determined whether these patients gain further benefit from adding a CDK4/6 inhibitor to their endocrine therapy. The findings come from an analysis of serum samples from 432 women with breast cancer who took part in the S0226 clinical trial, which was conducted by the SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).

“SWOG researchers have demonstrated that a blood serum test can identify which of these patients have a slow-growing disease that might be controlled with a simple aromatase inhibitor pill alone,” said Dr Lajos Pusztai, MD, DPhil, professor of medicine (medical oncology) at Yale Cancer Center, who is a co-author on the paper.

Study S0226 found that most women with metastatic hormone-receptor-positive breast cancer who have not had previous treatment for their metastatic breast cancer live longer when they get a combination of the endocrine therapy drugs anastrozole and fulvestrant than when they get just anastrozole.

However, not all patients see extra benefit from the combination; some do just as well on a single drug. Having a way to identify which patients would not derive added benefit from the combination could save these patients the additional side effects and extra costs associated with taking two drugs instead of one.

The work was led by Costanza Paoletti, MD, who was then with the University of Michigan Rogel Cancer Center. She and her colleagues measured the level of serum thymidine kinase 1, or sTK1, considered a marker of cellular proliferation, in 1,726 samples taken from S0226 patients before the start of their treatment and at four-time points during treatment.

The samples were evaluated using a commercially available test known as the DiviTum assay, produced by Biovica International of Uppsala, Sweden, which measures levels of the enzymatic activity of sTK1. The researchers found what was considered high levels of the enzyme in samples from 171, or 40 per cent, of the patients.

Patients with high sTK1 levels, either before treatment or at any time during treatment, tended to have a significantly shorter period of time before their disease advanced (progression-free survival time, or PFS). Those with high levels at the start of treatment, or baseline, had a median PFS of only 11.2 months compared to 17.3 months for patients with low levels at baseline.

The high-sTK1 patients also died sooner, on average, than patients with low levels of the biomarker, with median overall survival times of just 30 months versus 58 months.

Importantly, patients with low sTK1 levels did just as well on the single drug anastrozole as on the combination. This means a measurement of pretreatment sTK1 level could potentially be used to determine whether a patient should start treatment with two-drug endocrine therapy (high sTK1) or single-drug endocrine therapy (low sTK1).

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STUDY FINDS PRIMARY CAUSE OF CURRENT OBESITY EPIDEMIC

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A new study has claimed that much of the blame for the current obesity epidemic lies on modern dietary patterns characterised by excessive consumption of foods with a high glycemic load: in particular, processed, rapidly digestible carbohydrates.

These foods cause hormonal responses that fundamentally change our metabolism, driving fat storage, weight gain, and obesity. The findings of the study were published in ‘The American Journal of Clinical Nutrition’.

Statistics from the Centers for Disease Control and Prevention (CDC) show that obesity affects more than 40 per cent of American adults, placing them at higher risk for heart disease, stroke, type 2 diabetes, and certain types of cancer.

The USDA’s Dietary Guidelines for Americans 2020 – 2025 further says that losing weight “requires adults to reduce the number of calories they get from foods and beverages and increase the amount expended through physical activity.”

This approach to weight management is based on the century-old energy balance model which states that weight gain is caused by consuming more energy than we expend. In today’s world, surrounded by highly palatable, heavily marketed, cheap processed foods, it’s easy for people to eat more calories than they need, an imbalance that is further exacerbated by today’s sedentary lifestyles.

Overeating, coupled with insufficient physical activity, is driving the obesity epidemic. On the other hand, despite decades of public health messaging exhorting people to eat less and exercise more, rates of obesity and obesity-related diseases have steadily risen.

The study points to fundamental flaws in the energy balance model, arguing that an alternate model, the carbohydrate-insulin model, better explains obesity and weight gain. Moreover, the carbohydrate-insulin model points the way to more effective, long-lasting weight management strategies.

According to lead author Dr David Ludwig, Endocrinologist at Boston Children’s Hospital and Professor at Harvard Medical School, the energy balance model doesn’t help us understand the biological causes of weight gain: “During a growth spurt, for instance, adolescents may increase food intake by 1,000 calories a day. But does their overeating cause the growth spurt or does the growth spurt cause the adolescent to get hungry and overeat?”

In contrast to the energy balance model, the carbohydrate-insulin model makes a bold claim: overeating isn’t the main cause of obesity.

Instead, the carbohydrate-insulin model lays much of the blame for the current obesity epidemic on modern dietary patterns characterised by excessive consumption of foods with a high glycemic load: in particular, processed, rapidly digestible carbohydrates.

When we eat highly processed carbohydrates, the body increases insulin secretion and suppresses glucagon secretion. This, in turn, signals fat cells to store more calories, leaving fewer calories available to fuel muscles and other metabolically active tissues.

The brain perceives that the body isn’t getting enough energy, which, in turn, leads to feelings of hunger. In addition, metabolism may slow down in the body’s attempt to conserve fuel. Thus, we tend to remain hungry, even as we continue to gain excess fat.

To understand the obesity epidemic, we need to consider not only how much we’re eating, but also how the foods we eat affect our hormones and metabolism. With its assertion that all calories are alike to the body, the energy balance model misses this critical piece of the puzzle.

While the carbohydrate-insulin model is not new–its origins date to the early 1900s–The American Journal of Clinical Nutrition perspective is the most comprehensive formulation of this model to date, authored by a team of 17 internationally recognised scientists, clinical researchers, and public health experts.

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New research uncovers link between inflammation and pancreatic cancer development

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A new discovery from researchers at The University of Texas MD Anderson Cancer Center has clarified the long-established connection between inflammation and pancreatic cancer development.

The findings of the study were published in the journal ‘Science’. According to the study, pancreatic cells display an adaptive response to repeated inflammatory episodes that initially protects against tissue damage but can promote tumour formation in the presence of mutant KRAS.

The authors demonstrated that mutant KRAS — which is found in roughly 95 per cent of all pancreatic cancers — supports this adaptive response, leading to selective pressure to maintain the cancer-causing mutation.

“We discovered that a single transient inflammatory event induced long-term transcriptomic and epigenetic reprogramming of epithelial cells that cooperated with oncogenic KRAS to promote pancreatic tumours long after the inflammation was resolved,” said corresponding author Andrea Viale, MD, assistant professor of Genomic Medicine.

“In the setting of repeated pancreatitis, KRAS mutations can be acquired early on to limit tissue damage, suggesting the existence of a strong evolutionary pressure to select mutated cells and providing a possible explanation for the nearly universal presence of mutant KRAS in pancreatic cancers,” Viale added.

Inflammation has long been linked to tumour development in several cancer types, but the specific reasons behind this connection were previously unclear.

The research team, led by co-first authors Edoardo Del Poggetto, PhD, postdoctoral fellow, and I-Lin Ho, a graduate student in the Viale Laboratory, sought to study the effect of pancreatitis — a condition of inflammation in the pancreas linked with a higher risk of pancreatic cancer — on pancreatic epithelial cells.

The researchers stimulated transient inflammation in a model system of inducible KRAS-driven pancreatic cancer. Inflammation caused immediate pathological changes in pancreatic cells, but they resolved within one week.

However, activation of KRAS even months following the resolution of inflammation resulted in accelerated tumour formation compared with controls, suggesting that inflammation drives long-term changes in epithelial cells that cooperate with mutant KRAS to promote cancer development.

Deep molecular analysis of epithelial cells following a single inflammatory event demonstrated substantial reprogramming of gene expression and epigenetic regulation that persisted long after recovery of the tissue damage, a process the researchers termed “epithelial memory.”

This cellular reprogramming activated pathways related to cell survival, proliferation and embryonic development, which are similar to pathways active during cancer development. The cellular reprogramming caused by inflammation also facilitated the acquisition of acinar-to-ductal metaplasia (ADM), a reversible process in which pancreatic acinar cells acquire features of ductal cells.

Acinar cells are responsible for producing and secreting digestive enzymes, while ductal cells are responsible for delivering those enzymes to the small intestine. ADM, a process that normally occurs in response to pancreatic damage, is thought to be a pancreatic cancer precursor.

In the context of epithelial memory, repeated inflammatory episodes resulted in the rapid and extensive appearance of ADM with minimal signs of cellular damage, suggesting that cellular reprogramming protects the pancreas against an accumulation of tissue damage. These findings also clarify that ADM is not a cancer precursor state, but rather an adaptive response to inflammation. Previous research has shown that KRAS mutations can induce and stabilise ADM.

Here, the authors demonstrated that induction of mutant KRAS during repeated inflammations resulted in more pronounced ADM and virtually no tissue damage. Thus, the authors predict that cells undergoing inflammation would have a strong positive selection for KRAS mutations or other alterations that stimulate ADM and limit damage accumulations.

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MOTHERS ARE NOW HESITANT TO HAVE ANOTHER BABY DUE TO COVID-19 PANDEMIC

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New study reveals nearly half of New York City mothers who had been trying to have another baby before the coronavirus pandemic began stopped in the first few months of the outbreak.

The findings of the study were published in the journal ‘JAMA Network Open’. Led by researchers at NYU Grossman School of Medicine, the survey of 1,179 mothers in New York City also found that one-third of women who had been thinking about becoming pregnant before the pandemic but had not yet begun trying said they were no longer considering it.

“Our findings show that the initial COVID-19 outbreak appears to have made women think twice about expanding their families and, in some cases, reduce the number of children they ultimately intend to have,” said study lead author and epidemiologist Linda Kahn, PhD, MPH.

“This is yet another example of the potential long-lasting consequences of the pandemic beyond the more obvious health and economic effects,” added Kahn.

Pregnancy becomes riskier and more difficult to achieve as women age, so the delays prompted by the pandemic may lead to increased health risks for both mother and child, as well as the need for costly fertility treatments, she added.

Kahn, an assistant professor in the Departments of Pediatrics and Population Health at NYU Langone Health, noted that all of the women in the study already had at least one child age 3 or younger.

As a result, it is possible that the challenges of caring for a young child during the peak of New York City’s outbreak and subsequent lockdown may have played a role in their hesitancy to have another baby.

Early evidence has already identified a birthrate decline in the United States during the coronavirus pandemic. Recent data showed that the country saw roughly 300,000 fewer births in 2020 than experts had expected based on annual fertility trends, with a particular drop in the last two months of the year, which corresponds with fewer conceptions at the beginning of the outbreak in March.

However, until now, few investigations have explored the root causes behind individual parents’ decisions to delay pregnancy. The new study is the first to examine pregnancy plans among mothers during the first wave of COVID-19 in New York City. For the investigation, the researchers analysed data from an ongoing pregnancy and child health study. In the survey, which collected data beginning in mid-April 2020, the mothers were asked to recall their pregnancy plans before the pandemic as well as whether they were still going forward with their plans at the time of the survey.

Among the findings, the study revealed that fewer than half of mothers who had stopped trying to become pregnant were certain they would resume trying to become pregnant once the pandemic ended, suggesting that they may abandon rather than just delay their plans to expand their families, Kahn said.

In addition, those with higher stress levels and greater financial insecurity were especially likely to postpone or end their plans for an additional child.

According to the study authors, this finding highlights the importance of financial health in parents’ decisions around pregnancy and suggests that additional financial support for families may be needed to address the nation’s ongoing fertility decline, which began in 2008.

“These results emphasise the toll the coronavirus has taken not only on individual parents but perhaps on fertility rates overall,” said study senior author epidemiologist Melanie Jacobson, PhD, MPH.

Jacobson, a research scientist in the Division of Environmental Pediatrics at NYU Langone, cautions that the investigation only included women who were planning to have children and did not account for unplanned pregnancies.

She said the study authors next plan to repeat the survey with the same group of mothers and explore the potential impact of vaccination, an option not available at the time of the survey.

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Research finds breastfeeding is being overtly discouraged by infant formula websites

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Despite public health efforts to support breastfeeding and informed choice, during a news study, an analysis of websites for baby formula manufacturers found that their messages and images discourage breastfeeding while touting the benefits of the formula.

The study, led by researchers at the NYU School of Global Public Health and published in the journal Public Health Nutrition, is the first to compare information and portrayals of breastfeeding with infant formula feeding on manufacturer websites directed at U.S. consumers. “Many factors influence parents’ decision to breastfeed or use formula, including breastfeeding support and work schedules. But we also know that marketing and advertising play a critical role,” said Jennifer Pomeranz, assistant professor of public health policy and management at NYU School of Global Public Health and the study’s lead author. “It is important to understand the messages caregivers are receiving directly from formula companies, whose websites are targeting pregnant women and new parents with marketing claims disguised as feeding advice and support.”

Breastfeeding has many well-documented benefits for infants and mothers. Because breast milk is a complete source of nutrition for babies and can protect them from infections and certain diseases later in life, the U.S. and global health authorities recommend breast milk as the sole source of nutrition during a child’s first six months and encourage continued breastfeeding.

Previous research shows that marketing from formula companies can influence norms and attitudes around infant feeding and may use unsubstantiated health claims to promote formula and diminish confidence in breast milk. To prevent this, the World Health Organization urges countries to ban the marketing of formula to consumers; while the U.S. still allows it, the Surgeon General recommended that infant formula be marketed in a way that does not discourage breastfeeding.

Pomeranz and her colleagues analyzed the websites of three major formula brands that make up 98 per cent of the U.S. market, as well as two organic brands, to compare messages and images about breastfeeding and breast milk with those about infant formula feeding.

The researchers found that substantial messaging on the five formula manufacturers’ websites focused on discouraging breastfeeding. The websites actually contained more messages about breastfeeding or breast milk than formula, but much of the breastfeeding content (40 per cent) focused on challenges, such as having a low supply of breast milk or difficulty latching.

The websites were significantly more likely to mention the benefits of formula (44 per cent)–for instance, statements that formula provides brain and gastrointestinal benefits–than benefits of breastfeeding or breast milk (26 per cent).

Moreover, manufacturers compared formula feeding to breastfeeding, rather than comparing their brands positively to other brands.

Images on the websites also illustrated the benefits of formula–including the ease of feeding, with babies holding their own bottles–while making breastfeeding look difficult and labour intensive.

“Infant formula manufacturers’ repeated communication about breastfeeding problems such as reduced breast milk supply or sore nipples, coupled with images of women holding their breasts to breastfeed, implies that breastfeeding is hard, painful work. These recurring messages may ultimately discourage breastfeeding,” said Pomeranz.

“Even if websites frame their ‘advice’ as providing solutions to the problems identified, it is completely inappropriate for a formula company to disseminate information–let alone negative information–about breastfeeding to new parents and mothers in particular,” added Pomeranz.

The researchers identified other marketing tactics on formula websites, including the use of discounts or coupons, contact information for sales representatives, and claims of health and nutritional benefits of infant formula over breast milk.

“These marketing practices directed towards U.S. consumers would be legally suspect in other countries, many of which follow W.H.O. recommendations and prohibit direct-to-consumer marketing of infant formula,” added Pomeranz.

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NEW INSIGHTS INTO FUNDAMENTAL WORKINGS OF IMMUNE SYSTEM IN RESPONSE TO SKIN CANCER THERAPY

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New research led by the University of Birmingham suggests that skin cancer patients could have a better prognosis if their T cells send messages from five specific genes in their immune response to drugs given to treat the disease.

The research, carried out in mice, cells in the laboratory, and using publicly available data from patients with advanced melanoma before and after treatment with Nivolumab therapy, was published in the journal Immunity. T cells are white blood cells that protect the body from harm from viruses, bacteria, and cancer cells and explore their environments by using their T cell receptor (TCR) to recognise fragments – called antigens – of microbes or damaged cancer cells.

The TCR controls the behaviour of the T cell and can send messages to the T cells’ command centre to kick-start an immune response. This process is important for vaccine research and treatment of autoimmune conditions but is particularly of interest for cancer treatments to improve the anti-tumour function of T cells.

The researchers carried out the study to better understand how the amount of antigen controls how the TCR sends messages to the T cells’ command centre, and how this affects the type of immune response. They wanted to explore how antigen amounts control the expression of so-called ‘immune checkpoints’ that act as brakes on immune responses. It is these immune brakes, such as one called PD1, that are the target of drugs that seek to increase the immune response in cancer immunotherapy.

Lead author Dr David Bending, of the University of Birmingham’s Institute of Immunology and Immunotherapy, explained: “Through our research, we discovered that the amount of antigen determined how many immune checkpoints or immune brakes a T cell had on its cell surface.

“When we exposed T cells to the highest amounts of antigen, they stopped sending signals to their command centre, and this was because they had increased the number of immune brakes, which shut down the messengers. This made these T cells unable to respond to antigens for a period.”

By blocking one of the immune brakes, called PD1, the researchers were able to re-awaken some of these ‘unresponsive’ T cells. They found that these re-awakened T cells not only started sending messages to their command centres, but the messages they sent were louder and clearer.

“The response from the command centre was that the T cells started to increase the number of messages from five specific genes,” added Dr Bending. “By looking for the messages from these five genes, we were able to show that these stronger and louder messages were increased in melanoma patients who survived for longer on drugs that block the immune brake PD1. We think that this means that those cancer patients whose immune cells can send messages from these five genes in response to drugs that target PD1, a good outcome is far more likely.”

The researchers said their finding shows that the immune system likely requires an optimal level of stimulation to mount the most effective immune response in skin cancer patients. Dr Bending added: “Our research gives us an interesting insight into fundamental workings of the immune system. It suggests that both the amount of antigen around a T cell and also the number of immune brakes the T cells have at their surface are very important in controlling immune responses. Furthermore, we have shown that we can alter the balance of the immune response through stopping some of these immune brakes, which results in a stronger T cell response.”

The study has generated a new potential readout to monitor patients on drugs targeting PD1 in cancer. It also may be useful for exploring the potential of combinations of drugs that target multiple immune checkpoints to try to further re-awaken T cells in cancer patients.

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