Day: 02/08/2012

Influence of preoperative chemotherapy for advanced thoracic oesophageal squamous cell carcinoma on perioperative complications.

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The Japan Clinical Oncology Group (JCOG) 9907 trial has changed the standard of care for advanced thoracic oesophageal cancer in Japan from postoperative chemotherapy to preoperative chemotherapy. The impact of preoperative chemotherapy on the risk of developing postoperative complications remains controversial. This article reports the safety analysis of JCOG9907, focusing on risk factors for postoperative complications.
METHODS: Patients with potentially resectable advanced thoracic oesophageal squamous cell carcinoma were randomized to either postoperative or preoperative chemotherapy followed by transthoracic oesophagectomy with D2-3 lymphadenectomy. Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. Clinical baseline data, intraoperative complications, postoperative complications and in-hospital mortality, collected on the case report forms in a predetermined format, were analysed. Univariable and multivariable analyses were used to explore the risk of postoperative complications in relation to treatment group, age, sex, tumour depth, nodal metastasis, stage and location.
RESULTS: Of 330 patients randomized, 166 were assigned to receive postoperative chemotherapy and 164 preoperative chemotherapy; 162 and 154 patients respectively underwent surgery. The incidence of intraoperative complications, postoperative complications and in-hospital mortality was similarly low in both groups. Multivariable analysis showed that age, sex and tumour location were independently associated with an increase in postoperative complications, but preoperative chemotherapy was not.
CONCLUSION: Preoperative chemotherapy does not increase the risk of complications or hospital mortality after surgery for advanced thoracic oesophageal cancer.

Source:BJCO

 

Amorcyte, a NeoStem Company, Enrolls First Patient in PreSERVE Phase 2 Trial for Acute Myocardial Infarction.

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Amorcyte, LLC, a NeoStem, Inc. company (NYSE Amex: NBS)(“NeoStem” or the “Company”) today announces the enrollment of the first patient in the Amorcyte PreSERVE Phase 2 trial for acute myocardial infarction. The study is a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of infarct-related artery infusion of AMR-001, an autologous bone marrow derived cell therapy enriched for CD34+ cells. AMR-001 is administered 5 to 11 days post-stent placement in patients diagnosed with an ST segment elevation myocardial infarction with ejection fraction less than or equal to 48%, as determined by cardiac magnetic resonance imaging measured after recovery from myocardial stunning. Approximately 160 subjects, age 18 and older, will be randomized 1:1 between the treatment group and control group. Progenitor Cell Therapy, LLC, also a NeoStem company, will support the manufacturing, product supply, and logistics for the trial.

Dr. Arshed Quyyumi, Professor of Medicine at Emory University and the lead principal investigator in the study said, “We are thrilled to begin evaluating AMR-001, a CD34+ cell therapy, in these patients. We look forward to Phase 2 trial confirmation of the biologic activity of AMR-001 demonstrated in the Phase 1 trial and hope to provide patients with significant clinical benefit and an enriched quality of life.”

“The first patient enrollment signals a key advance in our efforts in the trial,” said Dr. Andrew L. Pecora, Chief Medical Officer of NeoStem. “We are on track to enroll the targeted 160 patients over the next year or so with first data follow-up six months after the last patient is enrolled.”

AMR-001 represents the first compound in this class of cell therapies to have a highly defined cell population and an identified biologically effective therapeutic dose, both of which tie back to the biological mechanism of action that the outcomes of the current study are intended to demonstrate. The Amorcyte therapy is being developed initially for the preservation of heart muscle function for approximately 160,000 American patients who sustain a heart muscle damaging STEMI annually.

Dr. Pecora further added, “Even with current best clinical practices, this group faces a significant chance of adverse outcomes, including premature death. Our goal is to create significant pharmacoeconomic value by reducing the associated costs of adverse outcomes often seen in these patients. We feel AMR-001 has the potential to address a substantial unmet medical need.”

Source: NeoStem corporate presentation at www.neostem.com/investor-relations/.

 

Scientists develop biological computer to encrypt and decipher images.

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Scientists at The Scripps Research Institute in California and the Technion–Israel Institute of Technology have developed a “biological computer” made entirely from biomolecules that is capable of deciphering images encrypted on DNA chips. Although DNA has been used for encryption in the past, this is the first experimental demonstration of a molecular cryptosystem of images based on DNA computing.

Instead of using traditional computer hardware, a group led by Professor Ehud Keinan of Scripps Research and the Technion created a computing system using bio-molecules. When suitable software was applied to the biological computer, it could decrypt, separately, fluorescent images of The Scripps Research Institute and Technion logos.

A Union Between Biology and Computer Science.

In explaining the work’s union of the often-disparate fields of biology and computer science, Keinan notes that a computer is, by definition, a machine made of four components—hardware, software, input, and output. Traditional computers have always been electronic, machines in which both input and output are electronic signals. The hardware is a complex composition of metallic and plastic components, wires, and transistors, and the software is a sequence of instructions given to the machine in the form of electronic signals.

“In contrast to electronic computers, there are computing machines in which all four components are nothing but molecules,” Keinan said. “For example, all biological systems and even entire living organisms are such computers. Every one of us is a biomolecular computer, a machine in which all four components are molecules that ‘talk’ to one another logically.”

The hardware and software in these devices, Keinan notes, are complex biological molecules that activate one another to carry out some predetermined chemical work. The input is a molecule that undergoes specific, predetermined changes, following a specific set of rules (software), and the output of this chemical computation process is another well-defined molecule.

“Building” a Biological Computer.

When asked what a biological computer looks like, Keinan laughs.

“Well,” he said, “it’s not exactly photogenic.” This computer is “built” by combining chemical components into a solution in a tube. Various small DNAmolecules are mixed in solution with selected DNA enzymes and ATP. The latter is used as the energy source of the device.

“It’s a clear solution—you don’t really see anything,” Keinan said. “The molecules start interacting upon one another, and we step back and watch what happens.” And by tinkering with the type of DNA and enzymes in the mix, scientists can fine-tune the process to a desired result.

“Our biological computing device is based on the 75-year-old design by the English mathematician, cryptanalyst, and computer scientist Alan Turing,” Keinan said. “He was highly influential in the development of computer science, providing a formalization of the concepts of algorithm and computation, and he played a significant role in the creation of the modern computer. Turing showed convincingly that using this model you can do all the calculations in the world. The input of the Turing machine is a long tape containing a series of symbols and letters, which is reminiscent of a DNA string. A reading head runs from one letter to another, and on each station it does four actions: 1) reading the letter; 2) replacing that letter with another letter; 3) changing its internal state; and 4) moving to next position. A table of instructions, known as the transitional rules, or software, dictates these actions. Our device is based on the model of a finite state automaton, which is a simplified version of the Turing machine. ”

Unique Biological Properties.

Now that he has shown the viability of a biological computer, does Keinan hope that this model will compete with its electronic counterpart?

“The ever-increasing interest in biomolecular computing devices has not arisen from the hope that such machines could ever compete with electronic computers, which offer greater speed, fidelity, and power in traditional computing tasks,” Keinan said. “The main advantages of biomolecular computing devices over electronic computers have to do with other properties.”

As shown in this work, he continues, a wealth of information can be stored and encrypted in DNA molecules. Although each computing step is slower than the flow of electrons in an electronic computer, the fact that trillions of such chemical steps are done in parallel makes the entire computing process fast. “Considering the fact that current microarray technology allows for printing millions of pixels on a single chip, the numbers of possible images that can be encrypted on such chips is astronomically large,” he said.

“Also, as shown in our previous work and other projects carried out in our lab, these devices can interact directly with biological systems and even with living organisms,” Keinan explained. “No interface is required since all components of molecular computers, including hardware, software, input, and output, are molecules that interact in solution along a cascade of programmable chemical events.” He adds that because of DNA’s ability to store information, major computer companies have been extremely interested in the development of DNA-based computing systems.

Source: The Scripps Research Institute

 

Can Carotid Ultrasound Screening Motivate Smokers to Quit?

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In a randomized trial, screening was ineffective.

One possible role of cardiovascular (CV) screening tests is to motivate people with abnormal results to make lifestyle changes. To see whether this strategy works, Swiss researchers randomized 536 heavy smokers (age range, 40–70) to receive carotid ultrasound screening or no screening. Those with carotid plaques (58% of screened patients) received photographs of the plaques along with detailed explanations. Patients in both groups received intensive smoking cessation counseling.

Smoking abstinence rates at 1 year (confirmed by measurement of exhaled carbon monoxide and serum cotinine levels) were about 20% in both groups. Moreover, 12-month changes in CV risk factors such as lipid levels and blood pressure were similar in the two groups. Within the screening group, smoking cessation outcomes in patients with plaques did not differ significantly from outcomes in those without plaques.

Comment: Carotid ultrasound screening failed to motivate patients to quit smoking, over and above smoking cessation counseling. These findings — added to the evidence that patients with asymptomatic carotid stenosis who receive contemporary preventive medical therapies are unlikely to benefit from carotid revascularization suggest that carotid screening is not appropriate. An editorialist argues that, to motivate patients, improving patient–physician communication and relationships is a more-promising approach than ordering tests.

Source: Journal Watch General Medicine

Addressing Abuse of Neurology Patients.

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A position statement from the American Academy of Neurology.

The American Academy of Neurology has published a position statement on abuse of neurology patients, calling on neurologists to routinely screen for and address past or current abuse of their patients by family members or others.

The statement outlines definitions of abuse — including physical, emotional, sexual, child, and elder abuse — and lists the common neurological and psychiatric sequelae of abuse. The position statement also lists actions the clinician should take when dealing with abuse. The authors stress that these patients require appropriate referral to protective agencies, often emergently, and that such protection can result in increase in quality of life and reduction of neurological disability.

Comment: This position statement is welcome, given the frequency of abuse and violence toward patients with neurological disease, who, because of their disabilities, are exceptionally prone to such abuse and less able to deal with its consequences than are patients in other specialties. As the authors point out, violence may be the cause of the neurological dysfunction. Abuse may include combinations of the defined forms. For example, clinicians should always ask about child abuse when the spouse/partner is abused. Unfortunately, many states do not require the reporting of spousal abuse, although all states require the reporting of child, disabled-person, and elder abuse.

Clinicians must question patients alone, as the abuser may accompany the patient to the encounter. Many times, I have had to ask a partner to leave the room when I suspected abuse and often was rewarded by hearing details of great importance.

Two important points not emphasized in the position statement are as follows:

1) Physicians often suspect abuse for reasons that may be unclear even to them. Even if little objective information exists to corroborate this feeling, this does not excuse the physician from further investigation and action.

2) Because it is always easier not to act in the clinical setting, many instances of abuse are not pursued. On one occasion, I notified law-enforcement agents, who came to the clinic; when the offender became aggressive, he was arrested and handcuffed on the spot.

One quibbling point: Fibromyalgia is listed as a possible consequence of abuse. Assuming fibromyalgia is a discrete entity, how abuse may play a role in its development is unclear.

This position statement reminds physicians of their duties to patients and families; duties which, when carried out, may cause difficulties for the physician but are nonetheless required.

Source: Journal Watch Neurology

Preventing Catheter Thrombosis During Percutaneous Coronary Interventions.

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Heparin was more effective than fondaparinux at inhibiting clotting induced by the contact activation pathway.

Catheter thrombosis would seem to be an unlikely complication of percutaneous coronary intervention (PCI) because anticoagulants are used routinely during the procedure. One particular anticoagulant, fondaparinux, does not require monitoring and rarely induces heparin-associated thrombocytopenia. However, guide-catheter thrombosis is more common with fondaparinux than with heparin or enoxaparin low-molecular-weight heparin.

To investigate the mechanism of fondaparinux-associated catheter thrombosis, investigators from Canada analyzed clot formation on PCI catheter segments in vitro and developed a rabbit model to simulate the PCI procedure in vivo.

Plasma exposed to catheter segments clotted more rapidly than unexposed plasma (352 seconds vs. 971 seconds; P<0.05). This accelerated clotting was due to activation of factor XII and was dependent on the presence of factor XI; both factors are enzymes of the contact activation pathway. Heparin and enoxaparin attenuated contact-induced clotting, but fondaparinux had minimal activity (P<0.001 for the respective differences between the 3 anticoagulants). Further experiments confirmed that heparin was more effective than fondaparinux at inhibiting clotting induced by the contact activation pathway. In the rabbit model, catheter occlusion was delayed by heparin and enoxaparin but not by fondaparinux (P<0.05), although all three anticoagulants inhibited factor Xa to a similar extent. When small doses of heparin were given with fondaparinux, the time to catheter occlusion was longer than with either agent alone (P<0.05).

Comment: Catheter-induced thrombosis seems to be mediated by plasma contact activation factors. Because fondaparinux fails to inhibit these factors, it probably should not be selected for the prevention or treatment of catheter-induced thrombosis.

Source: Journal Watch Oncology and Hematology

 

Exemestane Associated with Increased Bone Loss in Postmenopausal Women .

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The aromatase inhibitor exemestane — used to treat early breast cancer in postmenopausal women and being considered for use in preventing the disease — worsens age-related bone loss, a Lancet Oncology study finds.

Researchers randomized some 350 women to receive exemestane or placebo. All were at increased risk for breast cancer, had no clinical evidence of bone-related disorders, and received calcium and vitamin D supplements.

After 2 years of treatment, the decline in bone-mineral density at the distal radius (the study’s primary endpoint) was 6.1% among exemestane recipients versus 1.8% among placebo recipients. Secondary endpoints, including density at the distal tibia and cortical thickness at the distal radius and tibia, showed similar changes.

The authors say the observed effects were likely secondary to loss of estrogen. And a commentator concludes: “Thus, one might not be too reassured about the use of exemestane in the prevention setting.”

Source: Lancet Oncology .

Bread, Poultry Account for Large Part of America’s Sodium Consumption.

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More than 40% of sodium consumed in the U.S. comes from 10 food categories, with bread and poultry among the top 5, according to an MMWR report.

CDC researchers examined data on some 7200 U.S. individuals aged 2 years and older who completed 24-hour dietary recalls as part of the 2007–2008 National Health and Nutrition Examination Survey. Overall, the mean daily sodium consumption (excluding table salt) was 3266 mg, well above recommendations to keep intake below 2300 mg.

The top 10 food categories contributing to sodium consumption were, in descending order: bread and rolls, cold cuts, pizza, poultry, soups, sandwiches, cheese, pasta mixed dishes, meat mixed dishes, and savory snacks. Two thirds of sodium came from foods purchased at stores; the rest came from restaurants, cafeterias, and other sources.

MMWR‘s editors suggest that clinicians advise most patients to read labels and choose lower-sodium foods.

Source: MMWR.

 

 

Intussusception Risk Not Elevated with Pentavalent Rotavirus Vaccine .

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The pentavalent rotavirus vaccine marketed as RotaTeq does not carry an increased risk for intussusception, according to a large U.S.-focused study in JAMA.

In response to international postlicensure reports showing increased intussusception risk, CDC and academic researchers examined data from eight U.S. managed care organizations to make two comparisons of risk rates. In one, infants who received recommended vaccines, but not one for rotavirus, were compared with infants who received RotaTeq. In the other, a historical cohort from 2001–2005 (before licensure of RotaTeq) was compared with RotaTeq vaccinees.

Neither comparison showed increased intussusception risk after RotaTeq, either in the first 7 or first 30 days after receipt of the vaccine.

The authors speculate that environmental or genetic factors may account for the increased risks previously found in international studies.

Source: JAMA

 

Are e-Patients expert in their own diseases?

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As an e-Doctor, one with some IT literacy, I welcome the e-Patient movement.

I think patients should be equipped, enabled, empowered, engaged, equals, and emancipated, as Wikipedia explains.  The link also adds “and experts” and here I have a problem, not because I don’t think patients should have access to knowledge or know a lot about their own disease, but because knowing one pattern of pathology, i.e. your own, does not make you an expert.

No more than, for example, a petty thief can call himself a criminologist.  An advocate, yes, certainly, but “expert” has the connotation of knowing everything there is to know about something. There may be expert patients out there, but I believe that denotation demands explanation, and e-Patient advocates and their blogs need to make sure that their information carries disclaimers that they do not have medical training or qualifications, and that the contents thereof are opinions, not medical advice. What makes someone an expert patient? I am an expert in sinus surgery, because I do the surgery so often.  I have also had the surgery myself, so I know what it feels like.  So I could be both.

My training took me twelve years of dedicated study, and another ten years of experience.  I base my decisions on the thousands of patients I have seen, with the collective knowledge of my training, continuing professional education, and experience.  For the common conditions in my field, I have seen the whole range of patient experience, from near disaster to an easy cruise.  I’m regularly surprised by diseases that present differently to the lists of symptoms in the textbooks, that respond unexpectedly well to treatments, or do not when there is little reason why they should not.  More than once I have “written off” patients as doomed to die, only to see them well and healthy years later, none of it due to anything I have done. As an “expert” I am surprised by how often I am wrong.

The longer I work as a doctor, the more I realize how little I know about why some patients do well and others not. I have learned not to prognosticate unless I really have to, or to be prescriptive or dogmatic in any sense, because there is a good chance I may be wrong.

So, to see e-Patients advocating certain treatments above others, saying “Do this and not that” based on their experience of one, is very unsettling.  I am medicolegally liable for the advice I give.  I don’t believe e-Patients should dispense medical advice without being equally liable for it.  It is a dangerous and counterproductive measure to ascribe success in overcoming serious disease against the odds to anything other than statistical probability. Because the guys who don’t do well cannot be there to offer their perspective.

Sure, having good and dedicated doctors helps, and access to new treatments, involvement in clinical trials etc. may make a big difference.  But that is no hope to the sufferer who is not winning the battle, or his/her family. The survivor’s views have a very real bias that may not be helpful to others with a disease.

For the same reason, anecdotal case reports in medical journals are useful in describing the wider spectrum of disease experience, but cannot be used to modify accepted treatments.  For that, we need properly done clinical trials involving hundreds or thousands of patients. e-Patients, for all their enthusiasm, may not know this.

On the other hand, the establishment of support groups, websites, educational forums that facilitate, share symptoms, and share experiences without necessarily offering advice are all great initiatives.  I welcome them.

The success of the e-Patient movement will depend on partnering with doctors, preferably e-Doctors, and developing systems around technology that benefit both parties and enhance medical care.

The true potential of the e-Patient movement is to set a new standard of care for medical practice.  No longer is medical information privileged.  Doctors need to beware for this reason – our standards of care have to meet the expectations of the educated, empowered and engaged patient.  We need to become e-Doctors.

An e-Patient will always need an e-Doctor.  We may not know as much about the nitty-gritty’s of your particular complaint, and will not feel it as you do, but our experience must count for something. The same can be said for our availability.

After all, Google does not do ER visits.

Source: by Martin Young is and CEO of ConsentCare./ BMJ blog.