In response to a lawsuit after a college football player died from complications due to sickle cell trait (SCT) during a workout, the NCAA implemented mandatory SCT screening of all Division I student-athletes.

A new study evaluated the impact of that policy and found that testing alone will help identify more than 2,000 athletes with SCT, but warns that screening alone will not prevent death.

“Although the policy is well-intentioned, screening is just the first step,” says Beth A. Tarini, M.D., M.S., lead author of the study and assistant professor in the Department of Pediatrics and Communicable Diseases at the University of Michigan. “In addition to educating athletes and staff, precautionary measures need to be strictly enforced.”

Tarini and her co-authors, M. Alison Brooks, M.D., a pediatric sports medicine physician at the University of Wisconsin, and David G. Bundy, M.D., an assistant professor of pediatrics with expertise in sickle cell disease at Johns Hopkins University, found that without a strictly enforced intervention, approximately seven NCAA Division I athletes would die suddenly as a complication of SCT during a 10-year period.

“In the end, enforcing safe training measures to protect all NCAA student-athletes – not just those in Division I – from sudden death related to SCT will benefit all athletes,” says Tarini. “That’s a win-win situation from a policy perspective.”

The association between SCT and overexertion was first identified by the U.S. military in the 1970s. Instead of implementing a universal screening policy, the military enforced a universal intervention program and was successful in preventing all subsequent sudden death in recruits with SCT.

Tarini, Brooks, and Bundy found that the NCAA screening program requires that 144,181 student-athletes from a four-year cohort would need to be screened to prevent one death – assuming 100 percent intervention – and would cost somewhere between $1.4 and $3 million. A universal intervention policy like the one implemented in the U.S. military could prevent all deaths associated with SCT and overexertion as well as death among other athletes from other life-threatening complications like cardiovascular conditions.

“The culture in sports to push ourselves dangerously beyond our limits is powerful,” says Tarini. “Implementing policies to identify those at risk provides a false sense of security if we aren’t diligent about monitoring and protecting the health and safety of our student-athletes.”

Tarini and colleagues analyzed NCAA reports, population-based SCT prevalence estimates, and published risks for exercise-related sudden deaths. They used these to estimate the number of sickle cell carriers and the number of potentially preventable deaths with mandatory SCT screening of NCAA Division I athletes. Using the most recently published, publicly available NCAA participation rates from academic year 2007-2008, they estimated the number of Division I athletes in a four-year cohort to be 81,073 males and 63,108 females.

New research published online in advance of print in the New England Journal of Medicine could refine the way that post-operative patients are cared for while preserving blood supply levels, an essential resource that is difficult to maintain at necessary quantities throughout the year. The study, led by researchers at UMDNJ-Robert Wood Johnson Medical School, shows that using a liberal blood transfusion strategy in post-operative hip-surgery patients did not appear to improve patients’ recoveries or reduce the rate of death, suggesting therefore, that utilizing a restrictive transfusion approach would be appropriate patient care and conserve blood.

“The need for, and the quantity of, transfusion of red blood cells in post-operative patients is controversial, but has not previously been evaluated in a large study,” said Jeffrey L. Carson, MD, the Richard C. Reynolds Professor of Medicine and study chair of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair, known as the FOCUS trial. “Our research shows that using a more restrictive transfusion approach could become the standard of care for post-orthopedic surgical, high-risk patients with underlying cardiovascular disease and save blood a precious resource.”

The study examined more than 2,000 high-risk patients, with a mean age of 82, with underlying cardiovascular disease or risk factors, and hemoglobin levels below 10 grams per deciliter, after hip surgery. Hemoglobin (Hb or Hgb) is the main component of red blood cells that carries oxygen throughout the body and is normally greater than 12 to 13 grams per deciliter. Patients commonly have a low hemoglobin level after surgery that results from bleeding and often receive red blood cell transfusion as treatment. However, the optimal level of hemoglobin at which blood transfusion should be administered has been unknown.

“This clinical trial is unique in that all patients were considered very high risk due to age and prior history of cardiovascular disease, including myocardial infarction (heart attack), or risk factors for heart disease,” said Dr. Carson.

Patients were randomly assigned a liberal transfusion strategy (transfusion if hemoglobin was less than 10 grams per deciliter) or a restrictive transfusion strategy (transfusion if hemoglobin was less than 8 grams per deciliter). Patients in the restrictive group also received a transfusion if they exhibited symptoms of anemia including chest pain, congestive heart failure or unexplained excessive heart rate. At 30 and 60 days post-surgery, there was no difference between the groups in the patients’ inability to walk without assistance nor was there a significant difference in the rate of death or heart attacks. Because the liberal transfusion strategy did not provide a benefit to patient outcomes as compared with the restrictive strategy, the study suggests that less blood transfusion may be appropriate and does not detrimentally affect patients’ recovery after surgery.

The FOCUS Trial was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. The study results, “Liberal or Restrictive Transfusion in High-risk Patients after Hip Surgery”, were published online today. Dr. Carson’s team of researchers at Robert Wood Johnson Medical School included: Helaine Noveck, MPH, deputy director, Clinical Coordinating Center; George G. Rhoads, MD, MPH, interim dean and professor at UMDNJ-School of Public Health; and Karen Dragert, RN, lead research nurse. He was assisted by investigators at the University of Maryland School of Medicine (Michael L. Terrin, MD, MPH, principal investigator, Data Coordinating Center, and Jay Magaziner, PhD, MSHyg) and from 47 hospitals in the United States and Canada.

Roughly half the people who get a serious blood clot in the leg experience lasting damage. Norwegian researchers are the first to show that a little-used supplementary treatment can help to prevent such complications.

Pain, swelling, itching, eczema and venous ulcers are characteristic signs of post-thrombotic syndrome, a condition developed by roughly half the patients who have experienced serious deep vein thrombosis, or blood clots in the leg.

In a study carried out in twenty Norwegian hospitals it has been demonstrated for the first time that a treatment to dissolve blood clots prevented such complications in a substantial number of patients. The treatment is called catheter-directed thrombolytic therapy.

No longer experimental

Catheter-directed thrombolytic therapy has been in modest use in Norway since the early 1990s and is known in other countries as well. But it is a costly treatment and until now its effect had not been documented.

“In our study we have shown for the first time that this treatment truly can reduce the long-term complications of blood clots in the legs,” says project manager Per Morten Sandset, a professor at Oslo University Hospital’s Department of Haematology. “This means it is no longer considered an experimental treatment and will likely be offered on a far larger scale.”

Dissolves blood clots

Roughly half of the study’s 209 blood-clot patients were randomly selected to receive standard treatment with blood-thinning medicine. The other half received thrombolysis in addition, administered via catheter and intended to dissolve blood clots.

The effects of the treatments were measured after six months and after two years, and will be measured again after five years. After two years, 41 per cent of patients who received both thrombolysis and conventional therapy had developed post-thrombotic syndrome (PTS) compared to 55 per cent of patients receiving conventional therapy only. Professor Sandset believes that refinements in the therapy will be able to substantially increase the rate of patients avoiding complications.

Open veins lower the risks

The study’s researchers observed a clear correlation between thrombolytic therapy, unobstructed veins and lower risk of developing PTS.

In thrombolytic therapy, patients receive medication through a catheter in the blood vessel and directly into the clot. This enables physicians to use a much lower dose than with conventional treatment, which is given intravenously.

The study also identified a drawback to thrombolytic therapy: increased risk of haemorrhaging. The researchers therefore recommend not using the treatment on patients at high risk for haemorrhage.

Loyola University Medical Center researchers are reporting what could become the first reliable method to predict whether an antidepressant will work on a depressed patient.
The method would involve a blood test for a protein called vascular endothelial growth factor (VEGF). A Loyola study found that among depressed patients who had higher than normal blood levels of VEGF, more than 85 percent experienced partial or complete relief from depression after taking escitalopram (brand name Lexapro®). By comparison, fewer than 10 percent of depressed patients who had low levels of VEGF responded to the drug.
“This would be the first time we would have a predictor for how well a patient would respond to an antidepressant,” said Angelos Halaris, MD, PhD, first author of the study. Halaris presented results during the 2011 annual meeting of the Society of Biological Psychiatry and the 4th Annual Illinois Brain, Behavior and Immunity Meeting.
About 60 percent of depressed patients do not respond fully to the first prescribed medication. Consequently, doctors often must prescribe a different medication again and again before finding one that works. “It would greatly benefit our patients if we could predict ahead of time whether a given medication would be effective for a certain patient,” Halaris said.
The Loyola study involved 35 patients who took escitalopram for major depressive disorder. Escitalopram belongs to a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Other common SSRIs are Prozac®, Paxil® and Zoloft®.
Scientists aren’t certain why SSRIs work in some patients but not in others. One possible mechanism is that SSRIs help restore a chemical balance in the brain. Some scientists recently have proposed a second possible mechanism, called neurogenesis — SSRIs help to regenerate brain cells in specific parts of the brain that have atrophied in depressed patients.
The Loyola study supports the neurogenesis theory. It appears that escitalopram, the SSRI used in the Loyola study, jump-starts brain cells that have become inactive. This regeneration is fueled by VEGF. In the brain, VEGF stimulates the growth of blood vessels and works in other ways to keep brain cells healthy and active.
It appears that in patients with higher levels of VEGF, there was more regeneration, helping to reduce depression. Conversely, in patients with lower VEGF levels, there was less regeneration of brain cells and less relief from depression.
If the finding is confirmed by further studies, it could lead to a blood test that would help physicians tailor treatment. If, for example, a patient had low levels of VEGF, the physician might skip SSRIs and try alternative classes of antidepressants, such as bupropion, or alternative therapies, such as psychotherapy or Transcranial Magnetic Stimulation (TMG). These treatments are all available at Loyola University Medical Center.
Currently, a VEGF blood test would be quite expensive if it were performed for a patient. But the cost likely would come down significantly if a VEGF test were to become widely used, Halaris said.

View drug information on Lexapro; Paxil CR; Prozac Weekly.

Patients need less blood after surgery than is widely thought. A new study comparing two plans for giving blood transfusions following surgery showed no ill effects from postponing transfusion until patients develop signs of anemia or their hemoglobin concentration falls below 8 g/dL.

Results of the National Heart and Lung and Blood Institute funded study are published in today’s edition of the New England Journal of Medicine. NewYork-Presbyterian Hospital/Columbia University Medical Center is one of 47 centers participating in the FOCUS (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) study, led by

Dr. Jeffrey Carson, Richard C. Reynolds Professor of Medicine at the UMDNJ Robert Wood Johnson Medical School in New Brunswick, NJ.

Dr. William Macaulay, a co-author and member of the FOCUS steering committee, says, “This study will help resolve the debate about how much blood patients need after surgery. More often than not, a blood transfusion isn’t necessary, even for elderly and sick patients.

“The implications are enormous. Reducing the number of blood transfusions will greatly decrease blood use, potentially saving an enormous amount of money,” continues Dr. Macaulay, director of the Center for Hip and Knee Replacement at NewYork-Presbyterian Hospital/Columbia University Medical Center, chief of the Division of Adult Reconstructive Surgery of the Hip and Knee, and the Nas S. Eftekhar Professor of Clinical Orthopaedic Surgery at Columbia University College of Physicians and Surgeons.

In the United States, 14.6 million units of blood are transfused each year. Between 60 and 70 percent of blood transfusions are given to patients undergoing surgery and the majority of blood transfusions are given to older patients. Commonly, patients are given a transfusion if their hemoglobin level is at or below 10 g/dL, although a growing number of physicians follow a “restrictive” approach using a lower threshold or symptoms of anemia. In addition, some physicians choose to give blood transfusions to patients with higher blood counts if they are elderly or have cardiovascular disease. Normally, people have blood counts above 12 g/dL.

The study followed 2,016 patients aged 50 years or older with a history of or risk factors for cardiovascular disease, who underwent surgery for hip fracture. They were randomized into two groups: one that received a transfusion when their hemoglobin level fell below 10 g/dL (liberal group) and another that received a transfusion when they had symptoms of anemia, or at a physician’s discretion if their hemoglobin was below 8 g/dL (restrictive group). The two groups had similar results for a large array of clinical outcomes, including risk for death within 60 days; functional recovery; risk for heart attack, infection, and falls; and symptoms such as fatigue. Median age was 82 years.

The difference in blood use was striking. Patients in the restrictive group received 65 percent fewer units of blood than the liberal group, and 58.5 percent of patients in the restrictive group did not receive any blood transfusion.

“As the medical community further embraces a restrictive approach to post-surgery blood transfusion, it’s important that physicians carefully evaluate patients for symptoms of anemia, and not just rely on hemoglobin levels. The patient’s body will often tell us when it needs blood,” says Dr. Macaulay.

The FOCUS trial confirms findings of the 1999 Transfusion Requirements in Critical Care Investigators (TRICC) trial, which found that outcomes of a 7 g/dL transfusion threshold and a 10 g/dL threshold were similar for patients in an intensive care setting. FOCUS did not find evidence of increased rates of death, heart attack, or congestive heart failure in its liberal group, despite anecdotal evidence.

People with low levels of iron in the blood have a higher risk of dangerous blood clots, according to research published in the journal Thorax. A study of clotting risk factors in patients with an inherited blood vessel disease suggests that treating iron deficiency might be important for preventing potentially lethal blood clots.

Each year, one in every 1,000 people in the UK is affected by deep vein thrombosis – blood clots that form in the veins. These can cause pain and swelling, but can also be fatal if the clot is dislodged and travels into the blood vessels of the lungs. Although some risk factors for blood clots are recognised, such as major surgery, immobility and cancer, often there is no clear reason for the blood clot.

To look for new risk factors for blood clots, scientists at Imperial College London studied patients with hereditary haemorrhagic telangiectasia (HHT). HHT is an inherited disease of the blood vessels, the main symptoms of which are excessive bleeding from the nose and gut. Previous research by the same group had found that HHT patients have a higher risk of blood clots, but the reason for this was unclear.

“Most of our patients who had blood clots did not have any of the known risk factors ,” said the paper’s lead author Dr Claire Shovlin, from the National Heart and Lung Institute at Imperial College London and an honorary consultant at Imperial College Healthcare NHS Trust. “We thought that studying people with HHT might tell us something important about the wider population.”

Dr Shovlin and her team analysed blood from 609 patients reviewed at the HHT clinic at Hammersmith Hospital from 1999 to 2011, to look for differences between the patients who had blood clots and those who did not. Many of the patients had low iron levels because of iron lost through bleeding. The researchers found that low levels of iron in the blood were a strong risk factor for blood clots. Patients who took iron supplements did not have higher risk, suggesting that treatment for iron deficiency can prevent blood clots.

“Our study shows that in people with HHT, low levels of iron in the blood is a potentially treatable risk factor for blood clots,” Dr Shovlin said. “There are small studies in the general population which would support these findings, but more studies are needed to confirm this. If the finding does apply to the general population, it would have important implications in almost every area of medicine.”

Iron deficiency anaemia is thought to affect at least 1 billion people worldwide. The association with blood clot risk might not have been found before because the iron levels demonstrating the link fluctuate during the day, and other markers of iron deficiency can be spuriously high if other medical conditions are present. Consistent timing of blood samples, as in this study, is therefore important for establishing correlations with health outcomes.

The link between iron levels and blood clots appears to be dependent on factor VIII – a blood protein which promotes normal clotting. High levels of factor VIII in the blood are also a strong risk factor for blood clots, and low iron levels were strongly associated with higher levels of factor VIII. The gene encoding factor VIII has sites where iron-binding proteins can bind, making it plausible that iron levels could regulate the factor VIII gene, and that this might be the mechanism for the link.

“We can speculate that in evolutionary terms, it might be advantageous to promote blood clotting when your blood is low in iron, in order to prevent further blood loss,” Dr Shovlin said.

A study published online in Nature Genetics reveals that scientists at the Washington University School of Medicine in St. Louis have uncovered a critical genetic mutation in some patients with myelodysplastic syndromes, which is are blood cancers that can progress to a fatal form of leukemia.

The researchers also established that patients with the mutation are evidently more likely to develop acute leukemia. Even though this finding needs to be confirmed in additional patients, the study could pave the way for genetic tests in the future that can diagnose the disorder more precisely and predict the course of the disease.

Researchers discovered the mutation in a gene known as U2AF1, whilst they were sequencing the entire genome of a 65-year old male with myelodysplastic syndrome that had progressed to leukemia. The researchers compared the mutation with the genome of his tumor cells, and subsequently also identified the genetic error in other patients with myelodysplastic syndromes, which indicates the significance of the mutation.

Senior author and hematologist/oncologist Matthew Walter, MD, assistant professor of medicine says:

“The mutation in this gene was not on anyone’s radar screen. In many cases, the diagnosis of myelodysplastic syndromes is unclear because there isn’t a straightforward diagnostic test. By understanding at the genetic level what is contributing to this disease, we hope to eventually improve the diagnosis and treatment of this disorder.”

Approximately 28,000 Americans above the age of 60 years are annually diagnosed with myelodysplastic syndrome, a hard-to-treat family of blood cancers that occur when blood cells in the bone marrow do not mature properly. The disease is incurable although drugs exist for treatment.

The disorder progresses to a form of acute myeloid leukemia in about 30% of cases, which usually ends in mortality, given that chemotherapy drugs are ineffective in these patients.

Doctors are currently evaluating what likelihood patients with myelodysplastic syndrome have in developing leukemia. They examine the tumor’s chromosomes to establish to which extent they broke apart and rearranged themselves, which indicates the severity of the disease.

First author Timothy Graubert, MD, associate professor of medicine, who specializes in treating patients with myelodysplastic syndromes explains:

“There are chromosomal patterns that indicate high risk and low risk, but the current methods to determine prognosis aren’t perfect.”

The researchers identified three patients with the U2AF1 mutation through whole-genome sequencing. They sequenced another 150 patients with myelodysplastic syndromes and identified 13 patients or nearly 9% with the mutation. They concluded that the mutations in each patient occurred during the development of myelodysplastic syndromes, seeing that they were not present in normal cells. Those patients who had a U2AF1 gene mutation were nearly three times more likely to develop leukemia compared with those who did not.

The researchers observed that in 15.2% of patients with mutation, the disorder progressed to leukemia compared with 5.8% of those without.

According to the findings, the most common mutation resulted in a single letter change in the DNA at a precise location in the U2AF1 gene. The researchers discovered, that the serine (a form of amino acid) in most mutation-positive patients tended be substituted by phenylalanine or tyrosine. They say that the mutation alone does not cause myelodysplastic syndromes but seems to be an early event in the course of the disease.

The U2AF1 gene usually makes a protein involved in splicing RNA, a sister molecule of DNA, which carries the instructions for building proteins.

Splicing brings together different sections of RNA that are needed to make a protein, whilst those sections that are not required are discarded. Even though the mutated version of the gene continues to produce a protein its splicing activity is changed, suggesting that it could be significant for the development of some cancers.

The new study adds to several new findings regarding the genetic basis of myelodysplastic syndromes. This study, alongside earlier studies published in Nature and the New England Journal of Medicine, have detected mutations in eight genes in patients with this disorder, which were involved in RNA splicing.

Grauber comments:

“Together, these findings are a real game-changer. A mutation in any one of these eight genes occurs in up to 50 percent of patients with myelodysplastic syndromes. Because these changes are so common, we think there are likely to be implications for improving the diagnosis of the disorder and finding new therapeutic options.”

Scientists at the Washington University School of Medicine and the university’s Genome Institute, including Richard Wilson, PhD; Elaine Mardis, PhD; Timothy Ley, MD; and Li Ding, PhD, all co-authors of the study, pioneered whole-genome sequencing for cancer. The new research is based on previous work to discover novel mutations in cancer by examining a patient’s entire genome.

The research was supported by the National Institutes of Health (NIH) and a Howard Hughes Medical Institute Physician-Scientist Early Career Award, and partly funded by a federal stimulus grant.

Petra Rattue

MSD announced the results of their Phase III study of vorinostat at the 53rd Annual Meeting of the American Society of Hematology (ASH). Vorinostat, designed for treatment in patients with progressive multiple myeloma, has met its primary endpoint in a Phase III study for investigational use in combination with bortezomib (Velcade®) by demonstrating a 23% reduction in the risk of progression in comparison to the standard therapy of bortezomib (p=0.01).

VANTAGE 088 (Vorinostat in Combination with Bortezomib in Patients with Relapsed/Refractory Multiple Myeloma: A Global Randomized Phase III Trial) is one of the largest trials conducted in patients with relapsed/refractory myeloma. The randomized, double-blinded, placebo controlled study was designed to show improvement in progression-free survival (PFS) in patients suffering from progressive multiple myeloma with at least one prior therapy, who were either treated with a combination of vorinostat and bortezomib, or with bortezomib alone.

The findings revealed that from 637 patients overall, the combination group had 417 PFS events with a 23% reduction in the risk of progression compared with a hazard ratio of 0.774 (0.64-0.94, p=0.01) in the bortezomib alone group.

The researchers noted that the average PFS in the vorinostat and bortezomib combination group was 7.6 months compared with 6.8 months in the bortezomib alone group.

The drugs were generally tolerated in the vorinostat and bortezomib combination group with adverse events consisting of thrombocytopenia, diarrhea, nausea, vomiting and fatigue. The researchers observed no difference in discontinuation rates due to an adverse event for vorinostat (21%) compared to the placebo group (22%).

At ASH, MSD also presented full results from VANTAGE 095 (Vorinostat in Combination with Bortezomib in Salvage Multiple Myeloma Patients), a global Phase IIb trial that involved 143 patients. The researchers determined the primary endpoint as overall response rate (ORR). According to the European Group for Blood and Marrow Transplant (EBMT), the vorinostat and bortezomib combination group achieved an ORR of 11.3%.

Petra Rattue

View drug information on Velcade.

According to study published in the New England Journal of Medicine, individuals who receive surgery require less blood after the procedure than commonly thought. The study compared two strategies for administering blood transfusions after surgery. The researchers discovered that no adverse effects from postponing transfusing were shown until patients hemoglobin concentration falls below 8 g/dL or they develop signs of anemia. The study was funded by the National Heart and Lung and Blood Institute.

NewYork-Presbyterian Hospital/Columbia University Medical Center is 1 of 47 centers taking part in the FOCUS (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) investigation.

The study was led by Dr. Jeffrey Carson, Richard C. Reynolds Professor of Medicine at the UMDNJ-Robert Wood Johnson Medical School in New Brunswick, NJ.

Dr. William Macaulay, a co-author and member of the FOCUS steering committee, explains:

“This study will help resolve the debate about how much blood patients need after surgery. More often than not, a blood transfusion isn’t necessary, even for elderly and sick patients.

The implications are enormous. Reducing the number of blood transfusions will greatly decrease blood use, potentially saving an enormous amount of money”

Dr. Macaulay is the director of the Center for Hip and Knee Replacement at NewYork-Presbyterian Hospital/Columbia University Medical Center, chief of the Division of Adult Reconstructive Surgery of the Hip and Knee, and the Nas S. Eftekhar Professor of Clinical Orthopaedic Surgery at Columbia University College of Physicians and Surgeons.

Each year in the U.S., 14.6 million units of blood are transferred. Individuals undergoing surgery receive between 60-70% of these transfusions. Older individuals received most of the blood transfusions. Usually, individuals receive a transfusion if their hemoglobin level is at or below 10 g/dL. However, an increasing number of physician’s follow a “restrictive” method using signs of anemia or a lower hemoglobin level. Furthermore, a few physicians decide to give transfusions to individuals who have cardiovascular disease or higher blood counts if they are elderly. Usually individuals have blood counts higher than 12 g/dL.

2,016 individuals aged 50+ with a history of or a risk for cardiovascular disease, were enrolled to participate in the study. Median age of participant was 82 years old. Participants were randomly assigned to two groups. One group received a blood transfusion when their hemoglobin level was below 10 g/dL (liberal group), while the other group (restrictive group) received a transfusion when they showed signs of anemia, or at a physician’s discretion if their hemoglobin level was less than 8 g/dL. For a large variety of clinical outcomes, including heart attack risk, infection, falls, symptoms such as fatigue, risk of death within 60 days and functional recovery.

Participants in the restrictive group received 65% less units of blood than the other group. 58.5% of participants in the restrictive group did receive a blood transfusion.

Dr. Macaulay, explains:

“As the medical community further embraces a restrictive approach to post-surgery blood transfusion, it’s important that physicians carefully evaluate patients for symptoms of anemia, and not just rely on hemoglobin levels. The patient’s body will often tell us when it needs blood.”

The FOCUS trial verifies discoveries of the 1999 Transfusion Requirements in Critical Care Investigators (TRICC) trial, which discovered that outcomes of a 7 g/dL transfusion threshold and a 10 g/dL threshold were comparable for individuals in an intensive care setting. No evidence of increased rates of death, heart attack, or congestive heart failure in its liberal group, despite anecdotal evidence was found.

Grace Rattue

Known for her poetry, letters, love affair and marriage to Robert Browning, Elizabeth Barrett Browning also left a legacy of unanswered questions about her lifelong chronic illness. Now, a Penn State anthropologist, with the aid of her daughter, may have unraveled the mystery.

Born in 1806, Barrett Browning suffered throughout her life from incapacitating weakness, heart palpitations, intense response to heat and cold, intense response to illnesses as mild as a cold, and general exhaustion in bouts that lasted from days to months or years. Her doctors were unable to diagnose or treat her illness, which apparently first appeared around age 13.

“Conjectures by modern biographers about Barrett Browning’s condition include anorexia nervosa, neurasthenia; tuberculosis; pertussis, an encephalomyelitis; non-paralytic poliomyelitis; paralytic scoliosis, or the lifetime effects of injuries to her spine from falling from her horse in early adolescence; opium addiction; and mental illness, including anxiety and agoraphobia,” Anne Buchanan, research associate in anthropology, reports in the current issue of Perspectives in Biology and Medicine.

Some even attribute her illness to defense against the inferior status and treatment of Victorian women, or simply to malingering.

Ellen Buchanan Weiss, Buchanan’s daughter, noted the symptoms recorded in Barrett Browning’s letters because the symptoms seemed so similar to those that she experienced. Buchanan Weiss has hypokalemic periodic paralysis (HKPP), a muscle disorder that causes blood levels of potassium to fall because potassium becomes trapped in muscle cells. The disorder was first described in 1874 in German and then in 1901 in English. Barrett Browning died in 1861, long before physicians would have any idea of HKPP.

Today, oral or intravenous potassium can prevent or stop an attack, but there is no cure for the disorder, which may be genetic, either inherited or caused by a sporadic mutation. According to Buchanan, there is slight evidence of an uncle in Barrett Browning’s family who may have suffered the same symptoms. While Elizabeth and Robert did have a son, he apparently had no offspring so there are no living descendants.

A variety of triggers can initiate weakness for people with a periodic paralysis, says Buchanan. Common triggers for people with HKPP include anything that increases secretion of insulin — alcohol, hunger or high carbohydrate foods — table salt, excessive heat or cold, sudden temperature change, illness, sleep, exercise or some medications. Symptoms of HKPP generally first appear at puberty.

Barrett Browning’s first bout occurred after a minor illness, which was followed by measles. Her health continued to decline, and although physicians were unable to diagnose her malady, one prescribed opium to which she became addicted for life. This illness lasted for more than a year and at times she was so weak she could not sit upright without support.

Barrett Browning writes in the diary that she kept during her 25th year of other triggers for her ailment. She notes becoming weak after eating a generous portion of honey, a substance that would increase insulin production. She reports an episode that followed an outing where she ran down a hill, was rained upon and thoroughly soaked.

Throughout her life, she suffered terribly during the cold damp winters in England, especially in London, and only found some relief after marrying Robert Browning and escaping to the warmer, milder climate of Italy.

Other incidents in her life that she recorded include suffering terribly after a day of religious fasting. Hunger is a strong HKPP trigger. Her letters to Browning, her 25th year diary and other letters to friends and relatives describe not only the symptoms of her disease, which mirror those of HKPP suffers and Buchanan Weiss specifically, but also a list of triggers that are now known to be specific triggers for HKPP.

After two years of declining health, Barrett Browning died on June 29, 1861, in Browning’s arms.

Buchanan notes that “many others have read these same descriptions, looking for clues to her illness, but my daughter’s experience with HKPP has given us a perhaps unique lens through which to view them.”