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A new study out of the University of Chicago Medicine shows the overall rate of preoperative stress testing for hip and knee replacements is and has been decreasing consistently since 2006. Still, researchers found, 30,000 out of every 100,000 stress tests performed each year were unnecessary, as the tests didn't decrease the frequency of complications such as heart attacks or stopped hearts.

Titled "Frequency and Outcomes of Preoperative Stress Testing in Total Hip and Knee Arthroplasty from 2004-2017," the study was published today in JAMA Cardiology.

Preoperative cardiac stress testing is used to assess the risk for heart problems, such as heart attacks, in patients scheduled for non-cardiac surgeries. Researchers analyzed the IBM Marketscan 2004-2017 Commercial and Medicare Supplemental Databases, which represent the health services of about 185 million employees, dependents and retirees in the United States.

Each year in the United States during the study period, more than one million knee and hip replacements were performed. These are two of the most common surgeries done in the country, trailing only cesarean sections and cataract surgeries.

"Stress testing is expensive," said Daniel Rubin, MD, UChicago Medicine Associate Professor of Anesthesia and Critical Care and study first author. "It can also delay the knee or hip replacement surgery and lead to other unnecessary tests that may not help a patient, overall."

According to Rubin, cardiac stress testing was introduced prior to surgery to improve outcomes in patients who may be more likely to have heart attacks or stopped hearts. But over time, research has indicated that an increased amount of stress testing hasn't led to a change in the outcomes of these patients.

And while most researchers who have studied this area agree that routine testing isn't indicative of improved outcomes, many physicians continue to administer these tests in spite of existing guidelines to the contrary from the American College of Cardiology and American Heart Association.

"Even though there may be clear guidelines," Rubin said, "you may find practitioners are unlikely to adhere to them because they don't know the information, they have outdated guidelines, or they feel their experience is better attuned to a specific patient's needs."

According to Rubin and co-authors, while there has been progress in reducing the number of tests since 2006, the study's findings suggest a continued opportunity for educational initiatives to improve the utilization of medical resources and reduce costs associated with unnecessary testing.

ANN ARBOR, Mich. - A new study, published in Transplantation, finds that risk of death from COVID-19 in organ transplant recipients may be based upon how the patient was treated.

"Using data from the COVID-19 Rapid Response Registry, we examined COVID-19 positive adult solid organ transplant recipients and non-transplant patients that were matched to them on age, race and whether they were admitted at the hospital or seen at an outpatient facility," says lead author of the study, Pratima Sharma, M.D., an associate professor of medicine and a transplant hepatologist at Michigan Medicine.

Sharma says the demographics of patients included in the study were also consistent with COVID-19 patient trends throughout the state of Michigan.

"Black Michiganders represent 15% of the total population in the state and account for 42% of COVID-19-related deaths, compared to white Michiganders who represent 75% of the population in the state and 26% of deaths from COVID-19," she says.

"These statistics are also valid for solid organ transplant recipients, and while Black patients account for one tenth of all organ transplant recipients in our University of Michigan Transplant Center, they represented two-thirds of the COVID-19 positive organ transplant recipients group in this study," she adds. "These results highlight the racial inequities that have overwhelmed the United States health care system during this pandemic."

The research team found that disease severity and intubation rates were similar among both solid organ transplant recipients and non-transplant patients, but organ transplant recipients needed more renal replacement therapy, which takes over functioning for the kidneys when they are failing.

While death due to severity of the virus was similar in both groups, the use of hydroxychloroquine treatment was associated with higher death rates among the organ transplant recipients.

"In fact, we found that the treatment of hydroxychloroquine among organ transplant recipients was associated with ten-fold higher risk of death compared to not using the treatment among the recipients," Sharma says.

Bethesda, MD (Oct. 1, 2020) -- Today, the American Gastroenterological Association (AGA) released the first results from the NIH-funded AGA Fecal Microbiota Transplantation (FMT) National Registry, the largest real-world study on the safety and effectiveness of FMT. Published in Gastroenterology, the registry reported that FMT led to a cure of Clostridioides difficile (C. difficile) infection in 90% of patients across 20 North American FMT practice sites. Few serious side effects were reported.

"While the value of fecal microbiota transplantation for treating recurrent C. difficile infection is clear from research studies, the potential long-term consequences of altering a patient's gut microbiota are not fully known," says Dr. Colleen R. Kelly, Associate Professor of Medicine at Brown University in Providence, Rhode Island and co-principal investigator of the AGA FMT National Registry. "Releasing the initial results of the AGA FMT National Registry is an important step toward understanding the true risk and benefits of microbiota therapeutics in a real-world setting."

This new report details effectiveness and safety outcomes from the first 259 patients enrolled in the registry between December 2017 and September 2019. Almost all participants received FMT using an unknown donor from stool banks. The most common method of FMT delivery was colonoscopy followed by upper endoscopy. Of the 222 participants who returned for the 1-month follow-up, 200 participants (90%) had their C. difficile infection cured with 197 of those requiring only a single FMT. Infections were reported in 11 participants, but only two were thought to be possibly related to the procedure. FMT response was deemed durable, with recurrence of C. difficile infection in the six months after successful FMT occurring in only 4% of participants. This data includes patients with co-morbidities, such as inflammatory bowel disease and immunocompromised status, who are typically excluded from FMT clinical trials.

"These initial results show a high success rate of FMT in the real-world setting. We'll continue to track these patients for 10 years to assess long-term safety, which will be critical to determining the full safety profile of FMT," added Dr. Kelly.

WHAT IS FECAL MICROBIOTA TRANSPLANTATION?

Fecal microbiota transplant, or FMT, is a medical procedure in which the stool from a healthy person is prepared and then put into the intestine of a sick patient. FMT is most commonly used to treat Clostridioides difficile infection, if antibiotics have not been able to get rid of the infection. Recurrent C. difficile infection is common and increasing within the U.S. It is associated with significant morbidity and mortality and frequent failure of standard medical treatments, making FMT a potentially life-saving procedure. Learn more in the AGA GI Patient Center.

A research team at Nagoya University in Japan has revealed that narrow-range ultraviolet (UV) irradiation using light emitting diodes (LEDs) safely increases serum vitamin D levels in aging mice and thereby prevents the loss of their bone and muscle mass. The findings were recently published in the journal Scientific Reports.

Decreased bone density (osteoporosis) and the loss of muscle mass and strength (sarcopenia) are age-related disorders. While there are some remedies for osteoporosis, there is no effective treatment for sarcopenia. Recently, a condition called osteosarcopenia -- osteoporosis and sarcopenia together -- which impedes the daily life activities of the sufferer, has also been observed among many elderly people.

Vitamin D is essential for healthy bones and muscles, and its deficiency is a possible cause of osteosarcopenia. Vitamin D can be produced when the skin is exposed to sunlight. However, the availability of sunlight depends on various factors like latitude, season, weather and patient mobility, which makes it difficult to obtain vitamin D consistently from sunlight alone. Indeed, it is known that many elderly people have a vitamin D deficiency.

The research team, consisting of Prof. Yoshihiro Nishida, Dr. Kazuya Makida, and colleagues at the Nagoya University Graduate School of Medicine, has been working to establish a method of supplying vitamin D in a safe and stable manner at low cost. "Unlike sunlight, LED-based UV irradiation could be a consistent and stable source of vitamin D," says Dr. Makida.

In a previous study, the team had revealed that narrow-range UV irradiation using LEDs -- which is an energy efficient light source -- increased serum vitamin D levels in animal models with vitamin D deficiency and thereby prevented their bone weakness. However, due to its wavelength and intensity, the UV-LED irradiation could have harmful effects on the human body.

In the new study, the team first conducted experiments to determine the minimal intensity and the minimal dose of UV-LED irradiation that would supply sufficient vitamin D with few side effects. The minimal intensity was found to be 0.16 mW/cm2 and the minimal dose 1,000 J/m2.

Next, senescence-accelerated mice (mice bred with accelerated aging effects) were irradiated by UV-LEDs set to these levels. As a result, the serum vitamin D levels, bone density, and muscle mass and strength were all observed to increase compared to those of mice that were not irradiated. The researchers also verified that the UV-LED irradiation did not damage the skin of the mice. Therefore, they concluded, irradiation with narrow-range UV-LED light with minimal intensity and dose can safely and adequately supply vitamin D to aged mice, thereby preventing osteosarcopenia.

The team is now developing a small portable UV-LED irradiation device. "This device could prevent or cure osteosarcopenia without medicine," says Professor Nishida. "It's a new concept of medical device that can be used in various healthcare institutions and at home. It will also reduce the burden on people who care for immobile elderly people. With this device, all elderly people will be able to get enough vitamin D, the same amount or more than from sunlight, in an easy and safe manner at low cost. It could be a promising approach for the prevention and treatment of this disease."

(Vienna, 01 October 2020) In a systematic review of the worldwide published data on "Venous thromboembolism (VTE) in COVID-19 patients", Cihan Ay, Stephan Nopp, and Florian Moik from the Department of Medicine I, Clinical Division of Haematology and Haemostaseology, now for the first time, provide an in-depth analysis on the risk of VTE in patients hospitalised for COVID-19. While hospitalized patients at general wards have a VTE risk between 5 and 11%, the risk of developing deep vein thrombosis or pulmonary embolism in critically ill patients is 18 to 28%.

"From the beginning of the COVID-19 pandemic, studies reported an increased rate of thrombosis and pulmonary embolism in patients with COVID-19. On the basis of these reports, but without robust evidence from controlled interventional studies, global treatment strategies were developed, recommending more intense thromboprophylaxis strategies. Our study now offers a better understanding of the underlying risk and, therefore, aids in individual treatment decisions based on accurate risk assessment for the different patient groups," reports Principal Investigator Cihan Ay.

Within their review of the literature, the authors assessed a total of 5,951 studies published in the field of VTE in COVID-19. Of those, 86 studies were found eligible for inclusion and reported rates of thrombosis and pulmonary embolism in COVID-19 patients. After excluding additional studies due to underlying risk of bias in a structured assessment, 66 studies (28,173 patients) were found eligible to perform a meta-analysis to provide a robust estimate on risk of VTE in COVID-19.

The main findings are as follows: the overall VTE risk in hospitalized patients with COVID-19 is 14%, despite rigorous thromboprophylaxis regimens in most studies. Further, high heterogeneity in VTE rates was found between different patient subgroups. The rate was highest in patients admitted to intensive care units, with 23% of patients suffering VTE. Patients admitted to general wards suffered VTE in 8% of the cases. These findings underline the high risk of VTE in COVID-19 patients.

In addition, the authors specifically focused on estimating the risk of potentially life-threatening pulmonary embolism. The result: "This risk is considerably higher than in other comparable serious medical illnesses and ranges between 10 and 18% in COVID-19 patients requiring intensive care. Further, astonishingly, deep vein thrombosis was detected in almost half of the hospitalised COVID-19 patients who had been systematically screened for thrombosis using ultrasound." These findings underscore the strong impact of COVID-19 on the blood-clotting system. In addition, an exploratory analysis revealed that patients who developed deep vein thrombosis or pulmonary embolism during hospitalization had significantly higher D-dimer concentrations at admission, a laboratory parameter that indicates an activated coagulation system. This finding might be used to help develop personalized, risk-stratified thromboprophylaxis strategies in the future.

In summary, the authors provide a detailed evaluation of the risk of VTE based on the severity of the disease. Future studies need to determine whether elevated D-dimer at hospital admission justifies intensification of anticoagulant treatment in hospitalized patients with COVID-19.

A new study found that continuous positive airway pressure (CPAP) treatment at night can lower daytime resting heart rates in patients with prediabetes who have obstructive sleep apnea, reducing their risk of cardiovascular disease.

The study, published Oct. 1 in the Journal of the American Heart Association, was conducted by Esra Tasali, MD, Director of the Sleep Research Center at the University of Chicago Medicine, and Sushmita Pamidi, MD, a sleep physician-scientist at McGill University in Montreal.

The discovery could potentially help the 1 billion people worldwide with obstructive sleep apnea, in which the prevalence of prediabetes and diabetes is over 60 percent. Furthermore, the vast majority of patients with obstructive sleep apnea are undiagnosed.

The study's findings are especially timely, given that people with diabetes or cardiovascular problems are among the most vulnerable to COVID-19.

"Any way we can improve cardiovascular health is more important than ever these days," Tasali said.

This randomized controlled trial studied people with prediabetes, a condition where blood sugar levels are higher than normal but not high enough to be considered diabetic. Those who used CPAP treatment for two weeks had a drop in their resting heart rate by four to five beats per minute, compared to those who received placebo. Notably, with optimal CPAP treatment, their heart rates were not only lower at night, but also during the day.

"That's significant," Tasali said, noting that a drop of even one beat per minute in resting heart rate can lower the mortality rate and future risk of developing cardiovascular disease.

"A four- to five-beat-per-minute drop in heart rate that we observed is comparable to what you would get from regular exercise," she added. "Our breakthrough finding is the carryover of the lowered resting heart rate into the daytime and the cardiovascular benefit of that."

Resting heart rate is key to a person's health and well-being. A high resting heart rate signals increased stress to the heart. It is a strong predictor of heart problems and death, the doctors said. Prior research has shown that in middle-aged people, every beat-per-minute increase in resting heart rate is associated with a 3% higher mortality rate.

Obstructive sleep apnea is a disorder that causes people to repeatedly stop breathing at night, decreasing oxygen intake and disrupting their sleep. It is a serious health concern, increasing the risk of cardiovascular conditions such as high blood pressure, stroke and heart attack. It makes people sleepy during the day and heightens their "fight or flight" stress hormones, elevating their resting heart rate all day and night.

Doctors use CPAP to treat obstructive sleep apnea. It keeps a person's airway open and oxygen levels steady during the night, thus lowers their heart rate. However, Pamidi isn't encouraging people to go online and buy the machine. Obstructive sleep apnea is a medical diagnosis that must be made by a doctor after a sleep study.

"Our recent findings urge people who have prediabetes, diabetes or sleeping problems to be screened for sleep apnea," Pamidi said.

Today, about 80% of sleep apnea cases are undiagnosed. An estimated 50% to 70% of people with prediabetes or diabetes have sleep apnea.

"The majority of patients don't make a connection as to how their sleep can affect their hearts. With regards to their sleep apnea, patients just think how sleepy they are the next day," Tasali said. "I always explain to my patients that sleep apnea can also be harmful to their cardiovascular health."

This study is the first to examine the impact of optimal CPAP treatment on daytime resting heart rate," said Pamidi. Before joining McGill, she was a clinical fellow and then faculty at UChicago Medicine's Division of Pulmonary and Critical Care Medicine.

In their earlier research, Tasali and Pamidi found that effective treatment of sleep apnea with CPAP improves blood sugar levels in prediabetic patients, reducing their risk of diabetes.

Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NS-ML) are rare human developmental disorders caused by mutations of the protein SHP2. Until recently, the mechanism of NS and NS-ML pathogenesis had been unclear, and nor is there any effective treatment for the disorders.

Now, however, researchers from the Shanghai Institute of Organic Chemistry (SIOC) of the Chinese Academy of Sciences have uncovered the mechanism that underlies the pathogenesis of NS and NS-ML.

They found that disease-associated SHP2 mutants acquire the capacity for liquid-liquid phase separation (LLPS) to boost enzymatic activity, leading to hyperactivation of the downstream cellular signaling pathway.

Phase separation has emerged as a fundamental mechanism that regulates various biological processes. However, very little is known about whether dysregulation of phase separation plays a role in human developmental disorders.

The team found that both NS and NS-ML mutations lead to gain-of-function LLPS of SHP2, explaining a long-standing puzzle as to why NS and NS-ML have similar clinical manifestations, although they have different SHP2 mutations.

According to the researchers, LLPS of SHP2 mutants is regulated by conformational changes in the SHP2 protein, and is potently inhibited by the SHP2 allosteric inhibitor ET070, providing a therapeutic strategy for targeting SHP2 LLPS as a way of treating SHP2-associated developmental disorders.

This work also suggests the exciting possibility of using LLPS as a pharmaceutical target for developing new drugs.

The team believes that this study will offer new insights for understanding the link between LLPS and human disease, which will greatly help in the development of therapeutic approaches for treating disease.

Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among patients aged 80 or older, finds a study published by The BMJ today.

These findings could help guide end-of-life care discussions with critically ill patients with covid-19 and their families, say the researchers.

Anecdotal reports of poor outcomes in critically ill patients with covid-19 who have had in-hospital cardiac arrest have prompted discussions on the futility of cardiopulmonary resuscitation (CPR) for these patients. However, data to guide these discussions are lacking.

To address this evidence gap, a team of US researchers set out to estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and CPR in critically ill adults with covid-19.

Their findings are based on data for 5019 critically ill patients (aged 18 years or over) with covid-19 admitted to intensive care units at 68 hospitals across the United States.

The results show that 701 (14%) of patients had in-hospital cardiac arrest within 14 days of admission to the intensive care unit, of whom only 400 (57%) received CPR.

Patients who had in-hospital cardiac arrest were older (average age 63 v 60 years), had more underlying health conditions (comorbidities), and were more likely to be admitted to a hospital with fewer intensive care unit beds.

Importantly, this suggests that hospital resources, staffing, expertise, strain, or other factors not captured in this study, could have had a major impact, note the researchers.

Patients who received CPR were younger than those who did not (average age 61 v 67 years). Among those who did receive CPR, only 12% (48 out of 400) survived to hospital discharge, and only 7% (28 out of 400) did so with normal or mildly impaired neurological status.

Most patients who survived to hospital discharge needed only a short course of CPR. Survival also differed by age, with 21% of patients younger than 45 years surviving compared with 3% of those aged 80 or older.

The researchers point to some limitations, such as being unable to assess the quality and timeliness of CPR and limiting data to the first 14 days after intensive care unit admission, potentially underestimating the true rate of cardiac arrest.

However, strengths included use of high quality, detailed data for a large number of patients who were followed until death or discharge.

As such, the researchers say cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival even when CPR is provided, particularly in patients aged 80 or older.

"Our study data could help inform patients, family members, and clinicians in complex decision making about patients with covid-19 who are at risk of cardiac arrest or who have experienced cardiac arrest," they conclude.

During the COVID-19 pandemic, many countries paused their breast cancer screening programmes. A new study, presented at the 12th European Breast Cancer Conference, suggests that the disruption to screening could result in an increase in the proportion of women who die of breast cancer.

However, the study also suggests that this risk can be lowered, for example by making sure all women who would have been screened during the pandemic do not miss out, even if they are now older than the upper age limit for screening.

Two further studies, also presented at the conference, show how the COVID-19 pandemic affected treatment and everyday life for women who were already diagnosed with breast cancer.

The screening study [1] was presented at the virtual conference by Lindy Kregting, a PhD student at Erasmus MC, University Medical Center Rotterdam, The Netherlands. She said: "Screening works by detecting cancers at an early stage when there are the best chances of successful treatment. Cancer screening programmes have never been this severely disrupted before, so we don't know what impact this will have.

"We wanted to investigate what the long-term impact on deaths from breast cancer might be and to look at which strategies would be most effective for re-starting breast screening programmes."

The researchers used an established modelling tool called MISCAN-Breast to simulate four different strategies for re-starting breast screening following six months of disruption:

a straightforward re-start after the delay where all screening continued in the order it was planned, meaning one in every four women would end up going for screening one less time in her life (delay),

a delay to screening, except for women due to have their first screening (delay except first screen),

a delay to screening, but temporarily raising the upper age limit to make sure women don't miss their final screen (delay with age increase),

and increasing capacity to ensure a full catch-up where all delayed screens were caught up in a six-month period following the disruption (full catch-up).

Their model was based on the Dutch breast cancer screening programme where women are invited for screening every two years between the ages of 50 and 75. Similar screening programmes exist in many other European countries, although the age range and screening intervals vary.

Based on the four scenarios, the model showed how much capacity would be needed - the number of screening tests and follow-up tests - and the effects each strategy would have on rates of breast cancer incidence and deaths.

Researchers found that the first scenario (delay) had the most damaging effect, with an estimated increase of 2.35 deaths from breast cancer for every 100,000 women in the next ten years.

Increasing capacity to achieve a full catch-up was the best-case scenario with an increase of only 0.13 deaths from breast cancer out of every 100,000 women in the next ten years. However, the researchers say that this surge in capacity is probably not feasible for most countries' health services.

The other two scenarios, delay except first screen and delay with age increase, fell between the two with respective increases of 1.98 and 1.85 in breast cancer deaths per 100,000 in the next ten years. Based on these findings, they suggest that a delay to screening with a temporary increase in the upper age limit could be the best option for most screening programmes.

Ms Kregting added: "Our study shows that a six-month delay is likely to lead to a modest but important increase in breast cancer death rates, but different strategies for re-starting screening have different outcomes. The best way to prevent deaths from breast cancer is to catch up with all the screening that was missing during the COVID-19 pandemic. However, we realise that most breast screening programmes will not have the extra staff and equipment needed to do this.

"We found that the next best option, and one that we think is feasible, is re-starting breast screening as normal after the delay but making sure that no woman misses out on her final invitation to screening, even if by now she is older than the upper age limit."

A second study [2] including 1051 women diagnosed with breast cancer from Utrecht in The Netherlands looked at how the COVID-19 pandemic affected their daily lives. The study found that 48% of women felt lonely during the pandemic.

The research also found that 31% of women were less likely to seek help from their GP, 27% were worried about the effects of the pandemic on their aftercare and 15% were less likely to seek help from their breast cancer physician.

The study was presented by Dr Claudia Bargon, a clinician and PhD student at University Medical Center Utrecht (UMC Utrecht). She said: "We know that medical services, including those for breast cancer patients, had to be rearranged during the crisis. We also know that social support can be of vital importance for many women who have been diagnosed with breast cancer and that support can be restricted by social distancing measures.

"Our study shows that women were less likely to seek medical help during the pandemic and that a high proportion of women suffered loneliness during lockdown. This suggests that patients need reassurance that they should seek medical help when they need it and that we need to enable patients to access mental health support, even if this needs to be delivered online rather than face-to-face."

A third study [3] compared a group of 41 women treated for breast cancer in March and April 2020 at the University Hospital of Sassari, Italy, with 42 women treated in March and April of the previous year.

Researchers did not find any difference in how many women had surgery for breast cancer, how long they waited for surgery or whether they had a procedure called sentinel node biopsy, which checks for signs that cancer has begun to spread to the lymph nodes under the arm. However, they did find that women operated on during the peak of the COVID-19 pandemic were less likely to receive immediate breast reconstruction following mastectomy (removal of the breast) or to receive an 'intraoperative regional nerve block', a procedure carried out during surgery to reduce the likelihood of suffering breast pain after surgery.

The work was presented by Dr Alessandro Fancellu, Associate Professor of Surgery at the University of Sassari. He said: "These two procedures do not have an effect on the risk of breast cancer returning; however, they do have an effect on women's quality of life following breast cancer surgery. We know that there could be a second peak of COVID-19 and, if that happens, we want maintain the highest possible standards for our patients."

Professor Giuseppe Viale is from the University of Milan and the European Institute of Oncology, Italy, and was not involved with the research. He said: "Around the world, our medical services have had to reorganise to cope with the challenge of COVID-19. It's really important that we understand the impact that this has had on diagnosing, treating and caring for breast cancer patients.

"These studies bring some reassurance because they suggest that the disruption brought to breast cancer screening, treatment and care has not been devastating. However, they do show where we can do better - for instance in encouraging women to seek any medical help or counselling they may need - and how we can get services such as breast screening back on track."

New results to be presented at the 12th European Breast Cancer Conference show that a test, which looks at the activity of 70 genes in breast cancer tissue, is possible to use in the clinic to identify patients with invasive lobular carcinoma (ILC) that is at high risk of recurring and progressing.

Adjuvant treatments, such as chemotherapy, radiation therapy or targeted therapies, are not usually offered to ILC patients after surgery as the disease is slow growing and often responds well to hormone treatment alone. So far, there has been little evidence that such treatments improve outcomes, but they can affect people's quality of life.

However, the 70-gene signature test (commercially known as MammaPrint) identified some ILC patients whose genetic make-up puts them at high risk of the cancer recurring if they are treated with hormone therapy alone. These patients may benefit from additional adjuvant therapy.

ILC is a type of cancer that begins in the milk glands (lobules) of the breast. It becomes invasive when the cancer cells start spreading beyond the lobules and has the potential to spread to the lymph glands and other parts of the body. It affects about 10% of people with invasive breast cancer. By comparison, invasive ductal carcinoma (IDC) accounts for about 80% of breast cancers in women. It begins in the milk ducts and grows into the surrounding breast tissue, and is often treated with radiation, chemotherapy, hormone therapy or targeted therapies such as trastuzumab and T-DM1, in addition to surgery.

Dr Otto Metzger, a medical oncologist at the Dana-Farber Cancer Institute and assistant professor at Harvard Medical School, Boston, USA, told the conference: "The decision about whether or not to treat patients diagnosed with invasive lobular carcinoma with chemotherapy is difficult. Results from earlier research, which I carried out with Professor Christos Sotiriou while I was at the Institut Jules Bordet in Belgium, indicated that 10 to 15% of ILC cases were classified as high-risk at a genomic level. These had worse survival outcomes when compared to those classified as low-risk."

In a statement before the conference, the principle investigator of the MINDACT trial, Professor Fatima Cardoso, Director of the Breast Unit of the Champalimaud Clinical Centre in Lisbon, Portugal, said: "In this sub-study of the MINDACT trial, we have investigated further the biology of ILC and have identified a subset of ILC patients who could potentially benefit from chemotherapy or other adjuvant treatments. Here we report for the first time the utility of the 70-gene signature test in a large group of patients with ILC in the MINDACT randomised phase III clinical trial. These results are important for clinicians to help them choose a precise treatment approach tailored to the individual patient. This work was possible due to generous support of the Breast Cancer Research Foundation."

A total of 6,693 women with early-stage breast cancer enrolled in the international MINDACT trial. Of these, 5,313 patients were included in the current analysis: 487 women had ILC, including 255 classic cases of the disease and 232 variants, and 4,826 had IDC. The tissue samples were reviewed by a central pathology service to ensure consistency in categorising the different types and variants of cancer. The patients were followed for an average (median) of five years after diagnosis.

The 70-gene signature test classified 16.2% of ILC as high genomic risk and 39.1% of IDC as high genomic risk. By comparing classic ILC to variants of ILC, it classified 10.2% of classic ILC and 22.8% of ILC variants as high genomic risk.

The researchers found that estimates for the proportion of patients surviving without the disease recurring (disease-free survival, DFS) or without the disease spreading to other parts of the body (distant metastases-free survival, DMFS) at five years were similar for both ILCs and IDCs that had been classified as high risk by the 70-gene signature test. DFS was 87.1% for IDC and 84.6% for ILC. DMFS was 92.3% for IDC and 89.4% for ILC.

Estimates for IDCs and ILCs that the 70-gene signature test classified as low risk were also similar. DFS was 92.5% for IDC and 92% for ILC. DMFS was 96.5% for IDC and 96.6% for ILC.

Dr Metzger said: "We found that DMFS and DFS estimates were similar for ILC and IDC classified as either low or high-risk by the 70-gene signature test. This suggests that the test has prognostic value for ILC. The incorporation of biological features defined by the 70-gene signature test in the treatment decisions for patients diagnosed with ILC should facilitate a complex decision-making process, that includes the extent of disease, other health conditions and patients' preferences."

Chair of EBCC12, Professor Nadia Harbeck, of the University of Munich (LMU), Germany, who was not involved with the study, commented: "The results of this study show that the 70-gene signature test may play a useful role in the clinic when doctors are considering whether their patients with invasive lobular carcinoma might benefit from treatments such as chemotherapy in addition to surgery.

"As only about 10% of patients with invasive breast cancer have ILC and, in this study, the 70-gene signature test classified only 16.2% as high-risk ILC, a retrospective series of patients could have failed to identify a potential benefit for adjuvant therapies from such a small sub-group of patients. This analysis of over 5,000 women with early breast cancer in the MINDACT trial is an important contribution to our knowledge of the best way of treating these women."

Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of early death (before age 70), finds a study published by The BMJ today.

These associations were stronger for deaths related to cardiovascular disease and when long and irregular cycles were consistently present during adolescence and throughout adulthood. They were also slightly stronger among women who smoked.

The results highlight the need to consider the menstrual cycle as a vital sign of general health in women throughout their reproductive lifespan, say the researchers.

Irregular and long menstrual cycles are common among women of reproductive age and have been associated with a higher risk of major chronic diseases including ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems.

But evidence linking irregular or long menstrual cycles with mortality is scant.

So a team of researchers based in the USA set out to evaluate whether irregular or long menstrual cycles throughout the life course are associated with premature death (before age 70).

Their findings are based on data from 79,505 premenopausal women (average age 38 years) with no history of cardiovascular disease, cancer, or diabetes who were taking part in the Nurses' Health Study II.

Women reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years.

During 24 years of follow-up, 1,975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease.

After taking account of other potentially influential factors, such as age, weight, lifestyle and family medical history, the researchers found that women who reported always having irregular menstrual cycles experienced higher mortality rates than women who reported very regular cycles in the same age ranges.

Mortality rates per 1,000 person years for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years.

Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges.

These relations were strongest for deaths related to cardiovascular disease than for cancer or death from other causes. The higher mortality associated with long and irregular menstrual cycles was also slightly stronger among current smokers.

This is an observational study, so can't establish cause, and the researchers point to some limitations, such as relying on recall of menstrual cycle characteristics, which may not have been completely accurate, and the potential for other unmeasured factors to have affected their results.

Nevertheless, as it is not possible to randomise women to different menstrual cycle characteristics, studies like this one represent the strongest evidence possible for this question.

However, strengths included the large number of participants with a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.

The researchers say the mechanisms underlying these associations are likely related to the disrupted hormonal environment. And they conclude that their results "emphasise the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women's general health status."

Even when a sudden cardiac arrest happens inside a top hospital, where a code blue team is readily available, most people won't survive.

This year, while researchers continued exploring how to improve dismal cardiac arrest survival rates, clinicians started noticing a new population of patients who seemed to be experiencing cardiac arrest quite often: those hospitalized for COVID-19 infection.

This sparked an observational study led by experts at the Michigan Medicine Frankel Cardiovascular Center and Brigham and Women's Hospital that leveraged data from 68 hospitals across the United States, just published in The BMJ.

Researchers reviewed data from more than 5,000 U.S. patients, including those at Michigan Medicine, who were hospitalized in the intensive care unit for COVID-19. Fourteen percent of them experienced cardiac arrest within two weeks of being admitted to the ICU.

"Cardiac arrest is common in older patients with COVID-19, and survival rates after an arrest are poor," says lead study author Salim Hayek, M.D., an assistant professor of internal medicine at Michigan Medicine and a cardiologist at the Frankel CVC. "This is the first multicenter study to investigate in-hospital cardiac arrest in people with COVID-19 infection."

Along with older patients, those more likely to experience cardiac arrest included Black patients as well as those admitted to hospitals with fewer ICU beds.

"One of the more interesting findings was that patients who were admitted to smaller hospitals were more likely to experience cardiac arrest," says co-senior author David Leaf, M.D., MMSc, an assistant professor of medicine at Harvard Medical School. "Further, admission to a smaller hospital was independently associated with an increased risk of death among those who received CPR."

The researchers encourage medical centers to consider how they'll manage high rates of cardiac arrest in their sickest patients with COVID-19, especially if future patient surges occur.

"In general, only around one-fifth of people survive in-hospital cardiac arrest," says co-senior author Brahmajee Nallamothu, M.D., M.P.H., a professor of internal medicine at Michigan Medicine and an interventional cardiologist at the Frankel CVC, who has extensively studied in-hospital arrest procedures and outcomes.

"The numbers for patients with COVID-19 look worse; however, younger patients who receive CPR have reasonable survival rates compared with other critically-ill patients, though less than 3% of people older than 80 who received CPR lived long enough to go home from the hospital."

CPR for patients with COVID-19

Some have questioned whether patients with COVID-19 should be given CPR. In addition to concerns about the effectiveness, there's also worry about the chances of health care providers becoming infected and being taken out of circulation because COVID-19 can spread during resuscitation. Hospitals have strict protocols in place that require providers be suited up in personal protective equipment before getting close to patients with a confirmed or suspected COVID-19 infection, but there is still a risk.

Despite these concerns, Hayek and colleagues found that all patients who did not have a do-not-resuscitate order received CPR. About a third of patients older than 80 received CPR, while more than three-quarters of those younger than age 45 did.

However, only 12% of those patients given CPR survived.

"These data should encourage people to have more discussions about end-of-life wishes, including decisions about resuscitation, ideally before anyone even becomes severely sick," Hayek says.

That's because in COVID-19, unexpected complications can arise quickly.

Leaf adds that the acute severity of illness may have played a larger role in the cardiac arrest rates than existing heart disease, which wasn't independently associated with arrest rates, such as in the case of one previously healthy COVID-19 patient without a cardiac history who experienced cardiac arrest four times.

Other common complications of COVID-19 include blood clots and acute kidney injury.

And going home from the hospital after surviving cardiac arrest and COVID-19 isn't the end of the health struggles; it's simply an initial victory.

Researchers say, in the small sample size of patients with COVID-19 who were able to leave the hospital after receiving CPR, nearly half of them (20 out of 48 people) went home with a moderate to severe neurological impairment.

This is the latest project to come from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) group led by Harvard's Leaf, which includes detailed data on patients with COVID-19 infection who were admitted to ICUs at one of 68 hospitals across the country between March and June.

"It's impressive that this group led by David and Salim got together under stressful times to put together such a wonderful resource for asking these real world questions," Nallamothu says. "It has provided those of us studying resuscitation in other contexts with invaluable information."

Along with individual researchers' support from the National Institutes of Health, the Frankel CVC funded this project in its pivot to address the pandemic with the COVID-19 Impact Researcher Ignitor Fund.

TXA, a drug that prevents severe bleeding after injury by inhibiting blood clot breakdown, is most effective when given soon after injury. Every 15 minutes treatment delay reduces its lifesaving potential by 10%. However, currently only 3% of UK trauma victims get TXA within an hour of injury.

The drug is usually given by intravenous injection (IV) but securing an intravenous line can take time and the drug has to be injected slowly.

This new research, led by the London School of Hygiene & Tropical Medicine (LSHTM) with partners including The Royal London Hospital and St George's Hospital, shows that TXA can also be given by intramuscular injection (IM), just like a flu jab, which requires less training and takes less time. They found that the drug is rapidly absorbed from muscles and there were no local adverse effects.

This means TXA can be given by first responders, greatly expanding access to urgent treatment. This could improve trauma care around the world, especially in low- and middle-income countries where most trauma deaths occur.

Dr Ian Roberts from LSHTM who led the study said: "An urgent injection of TXA is life-saving after serious injury but patients are not being treated fast enough. A rapid intramuscular injection given by first responders or paramedics could mean the difference between life and death. Intramuscular TXA is like a vaccine against trauma death."

Every year, around five million people worldwide die from injuries. More than 90% of trauma deaths occurring in low- and middle-income countries, and up to 80% of deaths occurring prior to hospital arrival. Tranexamic acid is the only proven lifesaving treatment.

Previously work by a global collaboration led by LSHTM showed that TXA can reduce deaths in injury victims by up to one third provided that it is given promptly.

In this study, 30 bleeding trauma patients admitted into two UK trauma hospitals were given the first dose of TXA intravenously, as per guidelines, but the second dose by IM injection. The team then collected blood samples, monitored injection sites and measured TXA concentrations.

The team found that intramuscular TXA is well tolerated with only mild and transient injection site reactions - some redness and transient swelling - nothing else. Importantly, TXA was rapidly absorbed from muscle reaching the levels needed to save lives within 15 minutes even in the sickest patients.

Dr Ian Roberts said: "The fact TXA can be given by intramuscular injection could be a game-changer for increasing the survival chances of trauma victims. A simple auto injector device that could be used by lay first responders or police officers - before the ambulance arrives - could save thousands of lives each year. It could also be used by wounded soldiers either on themselves or a buddy."

The research team is now working with the British military on an autoinjector for battlefield use. The authors acknowledge that this would need proper field testing before adoption.

New Rochelle, NY, September 30, 2020—There is an urgent need for objective markers for diagnosing concussion, or mild traumatic brain injury. The status of blood-based biomarker development and point-of-care testing are examined in a new Expert Panel Discussion published alongside the peer-reviewed Journal of Neurotrauma. Click here to read the Roundtable now.

A blood-based biomarker can overcome the limitations of current verbal tests for concussion. Specific biomarkers in the blood can also help detect brain trauma masked by other injuries or symptoms.

“These blood biomarkers go a step further in the assessment and characterization of brain injury. Even when there is not a critical need because it is clearly evident that this patient has a brain injury of some level, deeper enrichment and characterization of the injury by virtue of these biomarkers adds enormous value over and above our current clinical methods,” says panelist Michael McCrea, PhD, the Medical College of Wisconsin. 

“The accurate and rapid field diagnosis of a concussion is key to assuring that athletes and Service members are not put at risk for a second injury before recovery from the first. This roundtable provides the insight of five of the most experienced traumatic brain injury clinician investigators regarding the role of peripheral protein biomarkers for the objective diagnosis of TBI, and exciting new developments in point-of-care assay technology,” says Moderator Donald W. Marion, MD, MSc, Neurosurgery Consultant, The Defense and Veterans Brain Injury Center/GDIT.

The expert panel was comprised of Jeffrey Bazarian, MD, University of Rochester; Jessica Gill, RN, PhD, National Institutes of Health; Geoffrey Manley, MD, PhD, University of California at San Francisco; Michael McCrea, PhD, the Medical College of Wisconsin; and Ava Puccio, RN, PhD, University of Pittsburgh.

The Expert Panel Discussion was produced with support from Abbott.

Scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health have discovered bacteria linked to post-infectious hydrocephalus (PIH), the most common cause of pediatric hydrocephalus worldwide. Results of the study led by Pennsylvania State University with CII scientists and clinical colleagues in Uganda are published in the journal Science Translational Medicine.

Hydrocephalus is the most common indication for neurosurgery in children. Of the estimated 400,000 new cases each year, about half are estimated to be post-infectious, with the largest number of cases in low- and middle-income countries, especially sub-Saharan Africa. Neonatal sepsis often precedes PIH, although the manifestations of hydrocephalus typically emerge in the months following the neonatal period as cerebrospinal fluid accumulates so that cranial expansion garners medical attention. These infants typically die in early childhood without advanced surgical management.

Study co-first author Brent L. Williams, PhD, assistant professor of epidemiology at CII, examined cerebrospinal fluid (CSF) taken from 100 consecutive cases of PIH and control cases of non-post-infectious hydrocephalus (NPIH) in infants in Uganda, testing the samples for evidence of bacterial and fungal microorganisms. He found Paenibacillus species (bacteria) in CSF linked to cases of PIH, not controls. Williams further quantitated Paenibacillus species in infant CSF samples, finding a high burden of these bacteria in infected patients. The findings were subsequently independently confirmed, and a strain of Paenibacillus was isolated and characterized through further testing by Steven Schiff, MD, the study's senior author, and colleagues at Pennsylvania State University. The researchers also found that Paenibacillus quantity was associated with clinical measures of hydrocephalus based on brain imaging scores, as well as potential signs of infection based on immune cell counts in patients.

Co-senior author W. Ian Lipkin, MD, John Snow Professor and CII Director, noted that "this discovery has the potential to reduce morbidity and mortality of this central nervous system disease in millions of children in sub-Saharan Africa by shifting treatment from surgery to antibiotics and vaccines."

"Now that we have identified a pathogen that may be responsible for some cases of post-infectious hydrocephalus, we can develop new, more sensitive tests to quickly detect an infection, assess its severity, identify the source of such infections, and hopefully provide targeted treatments to prevent the development of hydrocephalus" added Brent Williams.