Author Interviews, Biomarkers, NEJM, OBGYNE / 06.01.2016

MedicalResearch.com Interview with: Stefan Verlohren, MD, PhD Consultant and Senior Lecturer Maternal-Fetal Medicine Klinik für Geburtsmedizin / Department of Obstetrics Charité Campus Mitte Berlin  Medical Research: What is the background for this study? What are the main findings? Dr. Verlohren: Preeclampsia affects 2–5% of pregnancies worldwide, and is a potentially life threatening syndrome for both mother and child. Treatment options for preeclampsia are very limited, with delivery being the only ‘cure’; however, early detection and monitoring are beneficial for improving maternal and fetal outcomes. Development of preeclampsia is very difficult to predict: its clinical presentation is variable and its signs and symptoms overlap with other conditions. There has been an unmet medical need for improved prediction of preeclampsia, i.e. predicting which women will develop preeclampsia and which will not. Women with suspected preeclampsia are often hospitalized until preeclampsia and related adverse outcomes are ruled out. Others who require hospitalization may be overlooked because their symptoms were nonspecific (e.g. headache). Preeclampsia has been linked with impaired function of the placenta. Placental development is highly dependent on blood vessel formation; before and during preeclampsia, levels of molecules involved in blood vessel inhibition or growth are altered in the maternal bloodstream. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) (a molecule that inhibits blood vessel growth) is increased and placental growth factor (PlGF) (a molecule that encourages blood vessel growth) is decreased. This study has established that the ratio of these two molecules (sFlt-1:PlGF) can be used to predict whether preeclampsia will develop or not. The sFlt-1:PlGF ratio can be calculated with a blood test (the Elecsys® sFlt-1 immunoassay and Elecsys® PlGF immunoassay). PROGNOSIS has validated the sFlt-1:PlGF ratio cutoff level of 38 for prediction of preeclampsia. For women with suspected preeclampsia, the Elecsys® immunoassay sFlt-1:PlGF ratio of 38 or below has a high negative predictive value to rule out preeclampsia or adverse fetal outcomes in the next week. A Elecsys® immunoassay sFlt-1:PlGF ratio of more than 38 indicates that preeclampsia or fetal adverse outcomes may develop in the next four weeks. In conjunction with other diagnostic and clinical information, the Elecsys® immunoassay sFlt-1:PlGF ratio can be used to guide patient management. (more…)
Author Interviews, Cancer Research, Lymphoma, NEJM / 24.12.2015

MedicalResearch.com Interview with: Dr. Michael van Leeuwen PhD Department of Epidemiology Netherlands Cancer Institute Amsterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Over the last decades cure rates for Hodgkin’s lymphoma patients have increased dramatically. Cure and long-term survival may, however, come at a price, in the form of an increased risk of second cancers and other late effects. Since the late 1980’s treatment of Hodgkin’s lymphoma has been changed towards smaller radiation target volumes and more effective, generally less toxic chemotherapy. In a study which included 3905 Hodgkin’s lymphoma patients treated between 1965 and 2000 in the Netherlands, the impact of these treatment changes on second malignancy risk was evaluated. Hodgkin’s lymphoma patients were between the ages of 15 and 50 years and had survived at least 5 years after treatment. During follow-up, 1055 second cancers were diagnosed in 908 survivors, corresponding to a risk of 4.6 times as high as the occurrence of cancer in the general population. Up to at least 40 years after treatment for Hodgkin’s lymphoma, survivors remained at increased risk for second cancers. The cumulative incidence of a second cancer was 33.2% at 30 years, compared with 9.6% in the general population, and 48.5% at 40 years, compared with 19.0% in the general population. Breast cancer was the most common second cancer reported followed by lung and gastrointestinal cancers. Thirty-year cumulative incidence was 16.6% for breast cancer, 7.1% for lower respiratory tract cancers, 7.0% for gastrointestinal cancers, and 3.7% for non-Hodgkin’s lymphomas. The risk of solid cancer after treatment for Hodgkin’s lymphoma was not lower among more recently treated patients (patients treated between 1989 and 2000) than among those who were treated in earlier time periods, despite changes in treatment. Nonetheless, patients treated with smaller radiation fields (e.g., a supradiaphragmatic field radiotherapy not including the axilla) were at a 63% lower relative risk of breast cancer as a second malignancy than if they received complete mantle-field radiotherapy. The lack of change in the cumulative incidence of solid cancers could be due to an incomplete adoption of the more modern radiotherapy concepts but may also be explained on the basis of a change in the chemotherapy regimens used in the 1990s. Because in the 1970’s many women exposed to high doses of alkylating agents were experiencing premature menopause, doses of alkylating agents were lowered over time to preserve fertility. However, early menopause introduced with the alkylating regimens was likely responsible for decreasing the breast cancer incidence. With the lower doses of the alkylating agents, this protection was taken away. The cumulative incidence of non-Hodgkin’s lymphoma and of leukemia (and the myelodysplastic syndrome) was, however, much lower among patients who were treated in the period from 1989 through 2000 than among those who were treated in the period from 1965 through 1976. For leukemia, the decrease in cumulative incidence is likely due to the much lower doses of alkylating agents used in Hodgkin’s lymphoma treatment in the 1990’s compared to earlier decades. It is important to realize that current common practice in radiation oncology, including involved-node or involved-site radiotherapy, three-dimensional conformal radiation treatment planning, and radiation doses of less than 36 Gy, was not applied in our study population. It is hoped that these changes may reduce the risk of solid cancer among patients treated after 2000. (more…)
Author Interviews, Immunotherapy, NEJM, Rheumatology / 24.12.2015

MedicalResearch.com Interview with: Prof. dr. D.L.P. Baeten MD Clinical Immunology and Rheumatology Academic Medical Center University of Amsterdam Amsterdam, The Netherlands Medical Research: What is the background for this study? What are the main findings? Prof. Baeten: Ankylosing spondylitis is a debilitating rheumatic condition which affects young adults and with NSAIDS and TNF inhibitors as only therapeutic option. Over the last years, we generated evidence that IL-17 is an important inflammatory mediator in this condition. In the two studies reported here in the NEJM, we demonstrate that IL-17 inhibition with secukinumab has a very profound and long-lasting effect on signs and symptoms as well as inflammation in ankylosing spondylitis patients, even in those patients that failed a TNF blocker before. (more…)
Author Interviews, Heart Disease, NEJM, Surgical Research / 17.12.2015

MedicalResearch.com Interview with: Dr. Jochen Reinöhl Consultant and Head of the ISAH team (intervention for structural and congenital cardiovascular diseases) Department of Cardiology and Angiology I  (Medical Director: Prof. Dr. Christoph Bode) University Heart Center Freiburg ∙ Bad Krozingen Medical Research: What is the background for this study? What are the main findings? Dr. Reinöhl: Aortic valve stenosis is a medical condition with very high short-term mortality. Previously its only treatment – therefore the gold standard – consisted of surgical valve replacement. Since 2007 transcatheter aortic-valve replacement (TAVR) can be considered alternative. Its impact on clinical practice, however, is largely unknown. TAVR numbers rose from 144 in 2007 to 9,147 in 2013, whereas surgical aortic-valve replacement procedures only marginally decreased from 8,622 to 7,048. For both groups in-hospital mortality, as well as, the incidence of stroke, bleeding and pacemaker implantation (but not acute kidney injury) decreased. (more…)
Author Interviews, HIV, NEJM, Sexual Health / 02.12.2015

MedicalResearch.com Interview with: Dr Jean-Michel Molina Department of Infectious Diseases Saint-Louis Hospital and University of Paris Diderot Paris France MedicalResearch: What is the background for this study? What are the main findings? Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years. The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine  TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP). Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost. In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection. The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines. (more…)
Author Interviews, NEJM, OBGYNE / 26.11.2015

MedicalResearch.com Interview with: Arri Coomarasamy, MBChB, MD, FRCOG Professor of Gynaecology and Reproductive Medicine University of Birmingham Medical Research: What is the background for this study? What are the main findings? Professor Coomarasamy: Progesterone is a natural hormone that is essential to maintain a healthy pregnancy, and more than 60 years ago clinicians and researchers began to ask if progesterone supplementation in the first trimester of pregnancy could help to reduce the risk of miscarriage for women with a history of recurrent miscarriage. The evidence achieved in some small controlled clinical trials conducted before the PROMISE (progesterone in recurrent miscarriage) trial suggested a benefit from progesterone therapy, but without sufficient certainty to usefully guide clinical practice. Five years after it began, the PROMISE trial has provided a definitive result. It is clear, it is important, and it is not the result that many anticipated. Our study of more than 800 women with a history of unexplained recurrent miscarriage has shown that those who received progesterone treatment in early pregnancy were no less likely to miscarry than those who received a placebo (or dummy treatment). This was true whatever their age, ethnicity, and medical history. (more…)
Author Interviews, Beth Israel Deaconess, Hepatitis - Liver Disease, NEJM / 18.11.2015

MedicalResearch.com Interview with: Dr. Michael P. Curry, MD Medical Director for Liver Transplantation Harvard Medical Faculty Physicians Beth Israel Deaconess Medical Center Medical Research: What is the background for this study? What are the main findings Dr. Curry: As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. For many years, the only treatment option for these patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents (DAAs) have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis. We conducted this Phase 3, open-label trial to assess the efficacy and safety of a fixed dose combination of sofosbuvir/velpatasvir with or without ribavirin for 12 weeks or sofosbuvir/velpatasvir for 24 weeks in patients infected with hepatitis C virus genotypes 1 through 6 and with decompensated cirrhosis. We found that treatment with sofosbuvir/velpatasvir resulted in high rates of sustained virologic response (SVR) and early improvements in hepatic function in this patient population. SVR rates were 83 percent  in patients who received sofosbuvir/velpatasvir for 12 weeks, 94 percent among those who received sofosbuvir/velpatasvir plus ribavirin, and 86 percent among those who received sofosbuvir/velpatasvir for 24 weeks. (more…)
Author Interviews, Dermatology, Melanoma, NEJM, UCSF / 13.11.2015

MedicalResearch.com Interview with: Boris C. Bastian, MD, PhD Professor of Dermatology and Pathology Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Bastian:  The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers. Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case. Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Immunotherapy, NEJM / 05.11.2015

MedicalResearch.com Interview with: Toni Choueiri, MD Clinical Director, Lank Center for Genitourinary Oncology Director, Kidney Cancer Center Senior Physician Dana Farber Cancer Institute Associate Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Choueiri: In the METEOR trial, we aimed to compare cabozantinib, a novel VEGFR, MET, AXL inhibitor to everolimus, a standard 2nd line option in advanced RCC. There is an unmet in this setting. Cabozantinib resulted in a median PFS of 7.4 months compared to 3.8 months with everolimus. Responses also were 4-times higher with cabozantinib-treated patients. At the interim OS analysis, there was a strong trend favoring cabozantinib.  (more…)
Author Interviews, Chemotherapy, Lymphoma, NEJM / 04.11.2015

Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021MedicalResearch.com Interview with: Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021   Medical Research: What is the background for this study? What are the main findings? Dr. Ruan: Mantle cell lymphoma is an uncommon subtype of non-Hodgkin lymphoma that primarily affects elderly populations. Conventional chemotherapy regimens are generally not curative, and may not be tolerated by many patients, underscoring the need for treatment alternatives.  Previous experience with immunomodulatory compound lenalidomide has shown favorable activity and was well tolerated in patients with relapsedMantle cell lymphoma.  We evaluated the efficacy and safety of the biologic combination with lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma (MCL). The main findings of the study showed that the combination was effective and generally well tolerated when given as induction and maintenance treatment. The overall response rate was 92%, with complete response rate of 64% in the 36 evaluable patients. Median duration of response has not been reached at a median follow up of 30 months.   Treatment was outpatient-based and quality-of-life was preserved for most patients. (more…)
Author Interviews, Diabetes, NEJM / 28.10.2015

Marcus Lind, M.D., Ph.D Department of Medicine, Uddevalla Hospital Uddevalla, Swede MedicalResearch.com Interview with: Marcus Lind, M.D., Ph.D Department of Medicine, Uddevalla Hospital Uddevalla, Swede Medical Research: What is the background for this study? Dr. Lind:  One of the main goals of the diabetes care is to reduce excess mortality in individuals with type 2 diabetes close to that of the general population. We want patients to have a similar life expectancy as individuals in the general population. Earlier studies have shown that targeting good glucose levels, blood lipid and blood pressure levels are beneficial with respect to decrease cardiovascular disease being the main cause for mortality. We wanted to evaluate the prognosis for individuals with type 2 diabetes today in Sweden. Further, earlier population-based studies have generally assessed mortality rates only on a group level whereas we believe the prognosis differs greatly depending on various factors such as how well risk factor control is obtained in clinical practice. The Swedish Diabetes Registry include more than 90% of all individuals with type 2 diabetes in Sweden and information of e.g. the glycaemic control, measured by a biomarker called A1c exists for most persons. There were 97% who had at least 1 measurement. Also most patients had information of other risk factors, among others renal complications which we believed were of special concern.  (more…)
Author Interviews, Infections, NEJM, OBGYNE / 24.10.2015

Alfredo Mayor Aparicio PhD Associate Research Professor Barcelona Institute for Global HealthMedicalResearch.com Interview with: Alfredo Mayor Aparicio PhD Associate Research Professor Barcelona Institute for Global Health Medical Research: What is the background for this study? What are the main findings? Dr. Mayor: The malaria parasite is a well-adapted pathogen which can persist and reappear in areas where infection is no longer circulating or at very low levels. Prevention of such reinfections and resurgences is critical for the current goal of malaria eradication. However, little is known about the determinants and consequences of malaria declines and resurgences. For this reason, understanding the relationship between malaria transmission, immunity and disease burdens is essential to rationalise malaria interventions aimed at reducing host-parasite encounters. We have described changes in prevalence among pregnant women delivering between 2003 and 2012 at antenatal clinics in Southern Mozambique, and showed that a reduction of malaria-specific immunity associated with drops in transmission is accompanied with an increase the severity of malaria infection among those women becoming infected. These results suggest that success of control and elimination activities may lead through a transitional period where infrequent infections will likely slowdown the rate of acquisition of host defenses and will be thus associated with more deleterious effects during pregnancy, thus requiring more precise diagnosis and surveillance methods, as well as improved prevention. (more…)
Author Interviews, NEJM, Orthopedics / 22.10.2015

MedicalResearch.com Interview with: Søren Thorgaard Skou PT, PhD Postdoc Research Unit for Musculoskeletal Function and Physiotherapy University of Southern Denmark Clinical Nursing Research Unit Aalborg University Hospital  Medical Research: What is the background for this study? What are the main findings? Response: Total knee replacement has been performed for decades. The number of procedures are increasing and is expected to reach 1 million procedures per year in the US alone in the near future, highlighting the associated future economic burden. However, no studies have compared it to non-surgical alternatives, even though this is important to investigate its effectiveness. We found that in patients with knee osteoarthritis eligible for total knee replacement, treatment with total knee replacement followed by non-surgical treatment (exercise, education, dietary advice, use of insoles, and pain medication) were associated with greater pain relief and functional improvement after 12 months than the non-surgical treatment alone. However, both groups had clinically relevant improvements, and patients who underwent total knee replacement had more serious adverse events. Furthermore, most patients who were assigned to receive non-surgical treatment alone did not undergo total knee replacement within the 12 months. (more…)
Author Interviews, NEJM, Pediatrics / 15.10.2015

Prof. Dr. Dirk Bassler, MSc Department of Neonatology Zurich SwitzerlandMedicalResearch.com Interview with: Prof. Dr. Dirk Bassler, MSc Department of Neonatology Zurich Switzerland  Medical Research: What is the background for this study? What are the main findings? Response: The lungs of preterm infants are very vulnerable and these infants frequently develop chronic lung disease, also called bronchopulmonary dysplasia (BPD). BPD is not only a problem of the lungs, it is also a major cause of early death in these infants and if they survive, their risks of respiratory problems in later life and neurodevelopmental impairment are increased when compared to infants without bronchopulmonary dysplasia. Few drugs are available to prevent or to treat BPD and up to this date, no licensed drug for this indication is on the market, neither in Europe nor the USA. Hence additional preventive strategies are needed to reduce the risk of BPD and inhaled glucocorticoids seemed to have a favorable benefit-risk ratio. Medical Research: What are the main findings? Response: A total of 863 preterm infants with a gestational age of less than 28 weeks from 40 study centers in 9 countries (8 European countries and Israel) participated in the Neonatal European Study of Inhaled Steroids (NEUROSIS). The study investigated whether inhaled budesonide, an anti-inflammatory glucocorticoid, would decrease the incidence of bronchopulmonary dysplasia and death in preterm infants. The results show for the first time that inhaled budesonide reduces the incidence of BPD in preterm infants, a finding that is statistically significant. However, in absolute numbers, more infants died during the study period in the budesonide group compared to the placebo group. This difference is not statistically significant and could be caused by chance. Budesonide had a statistically significant positive effect on two more prespecified secondary outcomes: it reduced the rate of infants requiring intubation after completion of study treatment and the frequency of surgery required to close a patent ductus arteriosus, a blood vessel connecting the pulmonary artery to the aorta. The rate of side effects was similar in the budesonide and in the placebo group. (more…)
Author Interviews, Chemotherapy, Lung Cancer, NEJM, UT Southwestern / 11.10.2015

David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with: David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited. Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells.  The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer. The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs. In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has. Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history. (more…)
Author Interviews, Brain Injury, NEJM / 07.10.2015

Prof. Peter JD Andrews Honorary Professor Department of Anaesthesia University of EdinburghMedicalResearch.com Interview with: Prof. Peter JD Andrews Honorary Professor Department of Anaesthesia University of Edinburgh  Medical Research: What is the background for this study? Prof. Andrews: Therapeutic hypothermia has shown considerable promise as a neuro-protective intervention in many species and models of cerebral injury in the laboratory. Clinical trials after neonatal hypoxic ischemic encephalopathy and cardiac arrest (global cereal ischemia) show signal of benefit. The outcome after traumatic brain injury (TBI) has not improved in the last 20 years. Clinical trials of prophylactic therapeutic hypothermia for neuroprotection after traumatic brain injury show a mixed outcome, however, the larger trials are all neutral or have a trend toward harm. Because traumatic brain injury is a heterogeneous pathology it has been suggest that the therapeutic hypothermia intervention should be adjusted according to response of a biomarker, to maximize benefit and limit any harms. The EUROTHERM3235Trial was a trial of therapeutic hypothermia to reduce brain swelling after traumatic brain injury. Brain swelling was measured by an intracranial pressure (ICP) probe directly inserted into the brain. Medical Research: What are the main findings? Prof. Andrews: Hypothermia successfully reduced intracranial pressure, but did not improve outcomes compared to standard care alone, with more than a third achieving a good outcome in the standard care group and one a quarter in the hypothermia group. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, NEJM / 05.10.2015

Dr. Paul Jeffrey Young MD Intensive Care Unit, Wellington Regional Hospital Wellington South, New ZealandMedicalResearch.com Interview with: Dr. Paul Jeffrey Young MD Intensive Care Unit, Wellington Regional Hospital Wellington South, New Zealand Medical Research: What is the background for this study? What are the main findings? Response: Fever is a response to infection that is broadly conserved across many animal species and it seems reasonable to presume that the components of the immune response have adapted to function optimally in the physiological febrile range.  We have previously shown that among patients with fever and infection, increasing degrees of fever in the first 24 hours in ICU are generally associated with reducing mortality risk after adjusting for illness severity.  Although acetaminophen (paracetamol) is commonly used to treat fever in the ICU, there are no previous data to demonstrate the safety and efficacy of this practice.  The HEAT trial was designed by a group of ICU clinicians to test the hypothesis that treating fever with acetaminophen in critically ill patients with infections would worsen outcomes, or more specifically that it would reduce the number of days patients spent alive and free from requiring intensive care. Medical Research: What are the main findings? Response: The primary finding was that early administration of acetaminophen to treat fever did not alter the number of ICU-free days in adult ICU patients with infections.  The mortality rates of acetaminophen and placebo patients were similar.  Patients who received acetaminophen had lower body temperature than patients who received placebo and did not have significantly more adverse events.  Acetaminophen use was associated with a shorter ICU stay than placebo among survivors and a longer ICU stay among patients who died. (more…)
Author Interviews, Heart Disease, NEJM, Surgical Research / 05.10.2015

Prof. Dr. med. Patrick Meybohm, MHBA Leitender Oberarzt Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie Universitätsklinikum FrankfurtMedicalResearch.com Interview with: Prof. Dr. med. Patrick Meybohm, MHBAConsultant for Anesthesiology and Intensive Care Medicine University Hospital Frankfurt Dept. Of Anesthesiology, Intensive Care Medicine and Pain Therapy Frankfurt Germany Medical Research: What is the background for this study? What are the main findings? Prof. Meybohm: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-Remote ischemic preconditioning group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, NEJM / 29.09.2015

Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer CenterMedicalResearch.com Interview with: Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Miller: Previous studies had found a small but real benefit with the addition of chemotherapy to anti-estrogen treatment in patients with hormone sensitive disease. The challenge for patients and clinicians has always been that the benefit of chemotherapy is quite small and the toxicity can be substantial. The Oncotype Dx recurrence score assay was developed to identify patients who could safely be treated with anti-estrogen therapy alone (and conversely those who truly need and would derive a much larger benefit from chemotherapy). When the Oncotype Dx RS was applied to samples stored from a previous randomized trial, patients with low risk scores didn't seem to benefit from chemotherapy. While those initial results had some impact on treatment, many were concerned about eliminating chemotherapy on the basis of one small retrospective trial. The overall trial enrolled 10,253 women. 1626 (15.9%) had a Recurrence Score of 0-10 and were assigned to receive antiestrogen therapy alone without chemotherapy. After five years 99.3% (98.7, 99.6%) for were free of distant relapse (that is to say, 99.3% of women had NOT had recurrence of breast cancer at distant sites in the body). Overall survival was 98%. (more…)
Author Interviews, Breast Cancer, NEJM, Radiation Therapy / 14.08.2015

MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes. Medical Research: What are the main findings? Dr. Poortmans: We found a decreased risk for development of distant metastases of 3% at 10 years, translated in a 3% overall improved overall disease free survival. Up to now, It leads to an improvement of 1.6% in overall survival at 10 years, which is, in contrast to the earlier 2 findings, just not statistically significant (borderline at p = 0.06). On the other hand, breast cancer related mortality is significantly improved and we did not see an increase in non breast cancer related causes of death. Overall toxicity was limited with only a significant increase in pulmonary toxicity, however to a low grade in the big majority of those patients. The benefit in overall survival is in a similar order of magnitude than adding for example taxanes to anthracycline-based adjuvant chemotherapy for a similar patient population as ours. Medical Research: What should clinicians and patients take away from your report? Dr. Poortmans:  First, we should appreciated that the regional (lymph node) recurrence rate is a poor endpoint for evaluation of also locoregional treatment. This can be explained by the fact that once distant metastases are found, no further search for local (breast) or regional (lymph nodes) recurrences is performed any more, as this is not relevant anymore for treatment or prognosis. However, the spread of distant metastases might occur from cancer involvement of the lymph nodes, explaining why we saw the effect of the lymph node irradiation basically only on the rate of development of distant metastases.  As a second message, we can appreciate that the 3% decreased distant metastases rate did not yet fully translate into a survival benefit, which can be explained by the need for even longer follow-up than 10 years. The explanation lies simply in the fact that even after development of distant metastases, patients can live for quite some more years with, however, only very little chance for definitive cure.  Thirdly, we demonstrated with the quality assurance programme linked to this trial that radiation treatment as used those days (the accrual phase was from 1996 until January 2004) radiation therapy techniques should be nowadays considered as suboptimal with a lack of full coverage of the target volumes and delivery of a too high dose to the organs at risk. With modern techniques, we expect that the results will even be quite better.  And finally, that the overall outcome of breast cancer improved a lot: at the start of the trial, we estimated overall survival at 10 years being 50%, which we revised in 2000 to 75% and we ended up with more than 80%. Thereby, it becomes more of a challenge to demonstrate benefits of further improving treatment as the same relative improvement will be translated into a lower absolute improvement. Nevertheless, by more effectively preventing the development of distant metastases by improved systemic therapy (or even better by earlier detection with a lower basal rate of distant metastases) the importance of optimizing locoregional control becomes even higher. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Poortmans: o First of all we have to improve our ability to define which patients will gain most from this treatment. o Secondly, we have to further investigate how to optimize the technical aspects of this loco regional treatment and … o Thirdly how to optimally integrate all treatment aspects including locoregional ones and systemic ones. o Based on all this, we can develop and then provide the patients with shared decision making tools. Citation: Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer Philip M. Poortmans, Ph.D., Sandra Collette, M.Sc., Carine Kirkove, Ph.D., Erik Van Limbergen, Ph.D., Volker Budach, Ph.D., Henk Struikmans, Ph.D., Laurence Collette, Ph.D., Alain Fourquet, Ph.D., Philippe Maingon, M.D., Mariacarla Valli, M.D., Karin De Winter, M.D., Simone Marnitz, M.D., Isabelle Barillot, Ph.D., Luciano Scandolaro, M.D., Ernest Vonk, M.D., Carla Rodenhuis, Ph.D., Hugo Marsiglia, Ph.D., Nicola Weidner, Ph.D., Geertjan van Tienhoven, Ph.D., Christoph Glanzmann, Ph.D., Abraham Kuten, M.D., Rodrigo Arriagada, M.D., Harry Bartelink, Ph.D., and Walter Van den Bogaert, Ph.D. for the EORTC Radiation Oncology and Breast Cancer Groups N Engl J Med 2015; 373:317-327 July 23, 2015 DOI: 10.1056/NEJMoa1415369 MedicalResearch.com is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Philip.Poortmans@radboudumc.nl MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands   Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes. (more…)
Author Interviews, Herpes Viruses, HIV, NEJM / 06.08.2015

Dr. Salim Abdool Karim at CAPRISA Doris Duke Medical Research Institute South AfricaMedicalResearch.com Interview with: Dr. Salim Abdool Karim at CAPRISA Doris Duke Medical Research Institute South Africa Medical Research: What is the background for this study? What are the main findings? Response: Globally, Herpes simplex virus type-2 (HSV-2) is among the most common sexually transmitted infections and is the leading cause of genital ulcers. Available global estimates indicate that approximately 417 million sexually active adults between the ages of 15 and 49 years had an existing prevalent HSV-2 infection in 2012. Current interventions to prevent HSV-2 infection, including condoms, circumcision, and antiviral treatment among heterosexual, HSV-2-discordant couples, have demonstrated protection levels ranging from 6% to 48%. This study showed that peri-coital tenofovir gel reduced HSV-2 acquisition in women by 51%, rising to 71% in high gel-users. (more…)
Author Interviews, Infections, NEJM / 22.07.2015

MedicalResearch.com Interview with: Alison E. Heald, M.D Harborview Medical Center Seattle, WA 98104 MedicalResearch: What is the background for this study? What are the main findings? Dr. Heald: Marburg virus causes a very serious, potentially fatal infection in humans for which there is currently no licensed or approved treatments or vaccines.  We demonstrated that AVI-7288, an investigational drug specifically directed against Marburg virus, is effective in preventing death in monkeys exposed to Marburg virus in an experimental model, and that AVI-7288 raises no safety concerns in parameters measured in the healthy human volunteers dosed at or above the estimated efficacious dose. Importantly, taken together, these results have allowed us to predict a dose that could be expected to protect humans exposed to Marburg virus. (more…)
Author Interviews, Dermatology, NEJM / 10.07.2015

Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg 07.04.2009 | Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg, Germany, 07.04.2009 | [© (c) Martin Zitzlaff, Emilienstr.78, 20259 Hamburg, Germany, Tel. +491711940261, http://www.zitzlaff.com, martin@zitzlaff.com, Postbank Hamburg BLZ 20010020 Kto.-Nr. 10204204, MwSt. 7%, Veroeffentlichung nur gegen Honorar (MFM) und Belegexemplar, mit Namensnennung] MedicalResearch.com Interview with: Prof. Dr. med. Kristian Reich DERMATOLOGIKUM HAMBURG Hamburg Medical Research: What is the background for this study? What are the main findings? Prof. Reich: The Phase 2b X-PLORE study compared a new generation biologic therapy, guselkumab - an inhibitor of IL–23, with the anti–tumor necrosis factor (TNF)–alpha agent adalimumab (Humira®) and placebo in the treatment of moderate-to-severe plaque-type psoriasis. It showed that up to 86 percent of patients treated with guselkumab achieved a Physician’s Global Assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study’s primary endpoint.  Interestingly, levels of efficacy were higher for several guselkumab doses through week 16 when compared to adalimumab. Improvements with guselkumab continued through week 40 with every eight- or twelve-week maintenance treatment.   (more…)
Author Interviews, Columbia, Diabetes, NEJM, Weight Research / 03.07.2015

Dr. F. Xavier Pi-Sunyer MD Division of Endocrinology and Obesity Research Center Columbia University, New YorkMedicalResearch.com Interview with: Dr. F. Xavier Pi-Sunyer MD Division of Endocrinology and Obesity Research Center Columbia University, New York Medical Research: What is the background for this study? What are the main findings? Dr. Pi-Sunye: In a large randomized trial, the drug Liraglutide was compared to placebo in overweight and obese non-diabetic volunteers. Over 52 weeks, in combination with diet and increased physical activity, Liraglutide lowered body weight by 8.4 kg as compared to 2.8 kg in placebo. 63% vs 27% lost at least 5% of baseline weight, 33% vs 10% lost more than 10% of baseline weight. (more…)
Author Interviews, Clots - Coagulation, NEJM / 23.06.2015

MedicalResearch.com Interview with: Dr. Charles Pollack Jr., MA, MD, FACEP Thomas Jefferson University Clinical Professor of Emergency Medicine Philadelphia, PA 19107 MedicalResearch: What is the background for this study? What are the main findings? Dr. Pollack: There are currently no approved specific reversal agents for non–vitamin K antagonist oral anticoagulants. Idarucizumab, an antibody fragment, was developed to specifically reverse the anticoagulant effects of the oral thrombin inhibitor, dabigatran. RE-VERSE AD is an ongoing, global Phase III patient study initiated in 2014 to investigate idarucizumab in emergency settings in patients taking dabigatran. We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who either presented with serious bleeding (group A) or required an urgent invasive procedure (group B) which could not be delayed by eight hours. We intentionally designed the study with very broad inclusion criteria to reflect the types of patients who would require urgent anticoagulant reversal in real-world emergency settings. The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. We also diligently collected clinical outcomes as secondary outcomes, being conscious that these may vary considerably due to the heterogeneity of the patients we included in the study. In our publication in the New England Journal of Medicine, we present the first results from the study, in an interim analysis of the data from the first 90 patients. The data showed that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in 88 to 98% of the patients who had had elevated clotting times at baseline. The reversal effect was evident within minutes. There were no safety concerns related to idarucizumab among the 90 patients involved in this study - including patients who were given idarucizumab on clinical grounds but were later found to have had normal results on clotting tests at baseline. This is consistent with the experience from the more than 200 volunteers who were administered idarucizumab in previous studies. (more…)
Author Interviews, Heart Disease, Karolinski Institute, NEJM, Technology / 11.06.2015

Jacob Hollenberg M.D., Ph.D. Assistant Professor, Cardiologist Head of Research, Centre for Resuscitation Science Karolinska Institutet, Stockholm, SwedenMedicalResearch.com Interview with: Jacob Hollenberg M.D., Ph.D. Assistant Professor, Cardiologist Head of Research, Centre for Resuscitation Science Karolinska Institutet, Stockholm, Sweden Editor’s note: Dr. Hollenberg and colleagues published two articles in the NEJM this week discussing CPR performed by bystanders in out-of-hospital cardiac arrests. MedicalResearch: What is the background for the first study? Dr. Hollenberg: There are 10,000 cases of cardiac arrest annually in Sweden. Cardiopulmonary Resuscitation (CPR) has been taught to almost a third of Sweden’s population of 9.7 million. In recent years the value of bystander CPR has been debated, largely due to a lack of a randomized trial demonstrating that bystander CPR is lifesaving. In this study, which included all cases of emergency medical services (EMS) treated and bystander-witnessed out-of-hospital cardiac arrests recorded in the Swedish Cardiac Arrest Registry from January 1, 1990, through December 31, 2011, our primary aim was to assess whether CPR initiated before the arrival of EMS was associated with an increase in the 30-day survival rate. MedicalResearch: What were the main findings? Dr. Hollenberg: Early CPR prior to arrival of an ambulance more than doubled the chance of survival. (30-day survival rate was 10.5% among patients who underwent CPR before EMS arrival, as compared with 4.0% among those who did not (P<0.001).) This association held up in all subgroups regardless of sex, age, cause of cardiac arrest, place of arrest, EKG findings or time period (year analyzed). MedicalResearch: How did the patients who survived cardiac arrest do from a disability standpoint? Dr. Hollenberg: We had cerebral performance scores from 474 patients who survived for 30 days after cardiac arrest. (higher scores indicate greater disability). At the time of discharge from the hospital, 81% of these patients had a score of category of 1. Less than 2% had category scores of 4 or 5. MedicalResearch: What should patients and providers take away from this report? Dr. Hollenberg:
  • For patients with an out-of-hospital cardiac arrest, CPR performed by bystanders before the arrival of emergency medical personnel, saves lives. This has been validated by both the size of this study and the consistency of the results over three decades.
  • CPR education needs to continue and to increase. In Sweden about one-third of the population has been taught CPR.       Legislation has recently been passed that mandates CPR be taught to all teenagers in school which should allow an entire generation to become familiar with this lifesaving technique.
  • The willingness of the public to become involved also needs to increase. We need new ways of educating lay people to recognize cardiac arrest and to motivate them to perform it. The knowledge that bystander CPR saves lives may enhance that motivation.
(more…)
Author Interviews, Fertility, Genetic Research, NEJM, University of Pittsburgh / 04.06.2015

Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213MedicalResearch.com Interview with: Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213 Medical Research: What is the background for this study? What are the main findings? Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem. We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies. (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, NEJM, Surgical Research, Yale / 31.05.2015

Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACSAssociate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT 06510MedicalResearch.com Interview with: Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven, Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT, Medical Research: What is the background for this study? What are the main findings? Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer -- the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease.  The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind.  No one likes to go back to the operating room -- so we asked the question, "How can we do better?".  Surgeons have debated various means of obtaining clear margins.  Some have advocated taking routine cavity shave margins -- a little bit more tissue all the way around the cavity after the tumor is removed at the first operation.  Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) -- i.e., selective margins.  We conducted a randomized controlled trial to answer this question.  We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit.  After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would ("NO SHAVE"), or take a bit more tissue all the way around the cavity ("SHAVE"). Patients in both groups were evenly matched in terms of baseline characteristics.  The key finding was that patients who were randomized to the "SHAVE" group half as likely to have positive final margins and require a re-operation than patients in the "NO SHAVE" group.  On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results.  While the volume of tissue excised in the "SHAVE" group was higher than in the "NO SHAVE" group, the distribution of patient-perceived cosmetic outcomes were identical in both groups.  Complication rate was also no different between the two groups.  We will be following patients for five years for long-term cosmetic and recurrence outcomes. (more…)
Author Interviews, NEJM, Pediatrics / 08.05.2015

MedicalResearch.com Interview with: Mr. Matthew A. Rysavy, B.S and Edward Bell, MD Department of Pediatrics, University of Iowa Iowa City, IA Medical Research: What is the background for this study? What are the main findings? Response: We were interested in understanding reasons for differences in outcomes among extremely preterm infants among hospitals.  This has been shown in many studies.  We found that differences among hospitals in whether treatment was initiated for infants born at very early gestations (22, 23, 24 weeks' gestation) accounted for a lot of the variation in hospital-level outcomes at these gestational ages. (more…)