NEJM This Week May 9, 2019
Welcome. This is the New England Journal of medicine. I'm Dr Michael bearer this week may ninth two thousand nineteen we feature articles on from the license for stroke up to nine hours after onset. Transmission of the Nipah virus in Bangladesh. Progesterone in women with bleeding in early pregnancy, a tight or reversal agent Mozelle, KOMO hammer Toma of the liver and Deisler one syndrome and inflammatory remarks about cardiovascular disease, a review article on chronic kidney disease in agricultural communities. A case report of a man with neck pain, and swelling and perspective articles on the current opioid crisis. And the Sackler legacy on stopping the gaps in epidemic preparedness on physician participation in lethal injection and on the meaning of the baseline mindset. A new video in clinical medicine demonstrates, elliptical excision of the skin this procedure can be used in the diagnosis and management of skin and subcutaneous lesions may be performed with minimal risk in most patients, and may avert the need for other more invasive procedures visit any jam dot org to view this video. Thrombosis guided by perfusion imaging up to nine hours after onset of stroke by Henry Ma from the university of Melbourne Park Ville, Victoria, Australia. The time to initiate intravenous thrombosis for acute ischemic stroke is generally limited to within four and a half hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have a schemic, but not yet infarct brain tissue on imaging in the extend trial patients with schemic stroke and salvageable brain tissue were randomly assigned to receive intravenous of place or placebo between four and a half and nine hours after the onset of stroke or an awakening with stroke if within nine hours from the mid point of sleep after two hundred twenty five of the planned. Three hundred ten patients had been enrolled, the trial was terminated because of a loss of equa poise after the publication of positive results from previous trial, the primary outcome of a score of zero or one on the modified Rankin scale at ninety days indicating no or minimal deficits respectively occurred in thirty five point four percent of patients in the outta place group and in twenty nine point five percent of patients in the placebo group symptomatic interests rebe real hemorrhage occurred in six point two percent of patients in the Aalto place group and in zero point nine percent in the placebo group. Among these patients who had schemic stroke and salvageable brain tissue, the use of Aalto place between four and a half and nine hours after stroke onset, or at the time, the patient awoke with stroke symptoms resulted in a higher percentage of patients with no. No or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the outta place group Randolph Marshall from Columbia University. New York writes in an editorial that the era of time based treatment with intravenous outta place in patients with acute stroke may finally be drawing to a close the battle. Cry of time is brain has reigned unopposed until now, although the study was terminated after only two thirds of the intended population were enrolled, the likelihood of a good outcome. A score of zero or one on the modified Rankin scale at ninety days was forty four percent higher in the outta place group than in the placebo group. This trial represents a major successful step in using an image guided approach to extend the seemingly immutable time. Limit for pharmacologic. Rumble ISIS in patients with acute stroke. The trial will need to be validated. It was stopped early. Going to the publication of results of another clinical trial, which was not truly a quivalent to the extent trial because it targeted patients who were likely to be eligible for thrombosis at the standard times and did not use pin number based image guidance further randomized clinical trials that compare intravenous thrombosis with Rahm beca me in the late time window among patients selected on the basis of pin. Number based imaging are warranted alternative from Belichick agents, such as connective place are also being tested despite the work to be done. The extent trial shattered an important barrier to the treatment of acute stroke. Transmission of Nipah virus fourteen years of investigations in Bangladesh by beer, get Nicolay from the attitude. Pesto Paris Nipah virus is a highly virulent ZOA nodding pathogen that can be transmitted between humans using data from all Nipah virus cases identified during outbreak investigations in Bangladesh from April two thousand one to two thousand fourteen this study investigated case patient characteristics associated with onward transmission and factors associated with the risk of infection. Among patient contacts of two hundred forty eight Nipah virus cases identified eighty two were caused by person to person transmission corresponding to a reproduction number that is the average number of secondary cases per case patient of zero point three three the predicted reproduction number increased with the case patients. Age and was highest among patients forty five years of age or older who had difficulty breathing case patients who did not have difficulty breathing infected zero point zero five times as many contacts as other case patients did Sierra logic testing of one thousand eight hundred sixty three as symptomatic contacts revealed no infections spouses of case patients were more often infected fourteen percent of fifty-six than other close family members. One point three percent of five hundred forty seven or other contacts zero point nine percent of one thousand nine hundred ninety six the risk of infection increased with increased duration of exposure of the contacts and with exposure to body fluids, increasing age and respiratory symptoms. Were indicators of infectivity of Nipah virus interventions to control person to person. Transmission should aim to reduce exposure to body fluids? Stopping the gaps in epidemic. Preparedness a perspective article by Jeremy Farrar from the Wellcome Trust London. I isolated in Malaysia in nineteen ninety nine Nipah virus rapidly went from unknown to endemic in Bangladesh, which has seen an outbreak almost every year since two thousand one large gaps remain in our understanding, however such as how the virus crossed India to spark in EPA democ in Kerala on the country's southwestern coast in two thousand eighteen several life threatening viruses have been identified for the first time in the twenty first century, the World Health Organization in conjunction with global experts has drawn up a list of nine known infectious diseases and one unknown disease x in a blueprint for research and development. These infections have the potential to cause public health emergencies, and we lack the. Tools to diagnose treat or prevent them. The world is therefore particularly vulnerable to these infections. And yet they've been neglected in research and development. The list is not exhaustive and many infections. Pose a major threat new patterns of viral emergence and spread are being driven by ecological and Sociologic changes such as climate change migration of vector species to new areas changing interactions between people and animals, increasing connectivity between communities more and faster. Travel urban is Asian and political, instability and conflict our preparations for EPA makes must keep pace with such changes. A randomized trial of progesterone in women with bleeding in early pregnancy by Ari kumarisami from the university of Birmingham in the United Kingdom bleeding in early pregnancy. Is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy in this trial, four thousand one hundred fifty three women at forty eight hospitals in the United Kingdom were randomly assigned to receive vaginal suppositories containing either. Four hundred milligrams of progesterone or matching placebo twice daily from the time at which they presented with bleeding through sixteen weeks of just station, the incidence of live birth after at least thirty four weeks of Jeff station was seventy five percent in the progesterone group and seventy two percent in the placebo group the sensitivity analysis in which missing primary outcome. Data were imputed resulted in a similar finding the incidence of adverse events did not differ significantly between the groups among women with bleeding in early pregnancy. Progesterone therapy administered during the first trimester did not result in a significantly higher. Incidence of live births than placebo in an editorial Michael Green from Massachusetts General Hospital. Boston writes that threatened abortion is defined as bleeding through the vagina with a closed cervix that occurs before the age at which a fetus would be viable ex utero. The estimate of the percentage of threatened abortions that progress to pregnancy loss has varied from ten percent to twenty percent or more. Thus most women who have bleeding in early pregnancy. Do not lose their pregnancies. But of course, there is justifiable interest in identifying a treatment that can improve the chance of the birth of a live born healthy baby among pregnancies at substantial risk of loss. Much of our modern understanding of the endocrine illogic features of pregnancy can be. Traced to the nineteen thirties when it was recognized that an anterior pituitary like hormone human, Corey onic Genotropin rose rapidly after implantation of the consensus, and then fell while estrin and pregnant dial levels rose rapidly for the remainder of pregnancy by nineteen forty. It was also recognized that an initial rise in these hormones followed by a premature fall was associated with spontaneous abortion, regardless of whether the pregnancy was recognized in retrospect, it is likely that the initial rationale for hormonal therapy. That is the observed fall in pregnancy hormone levels before pregnancy loss was in fact, a consequence rather than a cause of pregnancy failure the subsequent enthusiasm for hormonal therapy was driven by overestimation of the incidence of pregnancy loss in the absence of therapy. And by reports of seeming success in uncontrolled case series, the current trial of treatment for threatened abortion provides much needed information regarding both the true risk of pregnancy loss in the absence of treatment and the small statistically insignificant difference in the incidence of live births between treatment and expectant management in a contemporary context. Antibody based Tyke Cabral or reversal agent in healthy volunteers by Deepak Bhatt from Brigham and women's hospital heart and vascular center, Boston Taikang, galore is an oral p two y twelve inhibitor that is used with aspirin to reduce the risk of schemic events among patients with acute coronary syndromes or previous myocardial infarction spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with Tigres Laura as with other anti platelet drugs. The anti platelet effects of taika gore. Cannot be reversed with platelet transfusion, a rapid acting reversal agent would be useful this phase one trial evaluated intravenous PB to four five to a monoclonal antibody fragment that binds taika gore with high affinity as a Cabral or reversal agent in sixty four healthy volunteers after. Forty eight hours of Tikal or pre-treatment platelet aggregation was suppressed by approximately eighty percent PB two four five two administered. As an initial intravenous bolles followed by a prolonged infusion. Eight twelve or sixteen hours was associated with a significantly greater increase in platelet function than placebo as measured by multiple as-as taika gore reversal occurred within five minutes after the initiation of PB to four five two and was sustained for more than twenty hours. There was no evidence of a rebound in platelet activity after drug sensation adverse events related to the trial. Drug were limited mainly to issues involving the infusion site in healthy volunteers, the administration of PB to four five to a specific reversal agent for Takagi lower provided immediate and sustained reversal of the anti platelet effects of tycoon. Floor as measured by multiple essays. Ms ankle moham- are Toma of the liver and Deisler one syndrome by Maria up Alana's res from the Jewish General Hospital. Montreal MS Anka moham- are Toma of the liver NHL with a reported incidence of zero point seven cases per million population per year accounts for approximately ten percent of liver tumors in persons younger than twenty one years of age, and is the second most common benign liver tumor in children after he mentio- mo- children with M H L may present with an enlarging painless abdominal mass the tumor is characterized by primitive mic sword. Stromer with cystic -ly dilated bile. Ducts alterations involving chromosome nineteen q. One three are a recurrent underlying cause of 'em H. L? These alterations activate the chromosome nineteen micro Aren a cluster. Other cases remain unexplained. These authors described to children with M H ELS that harbored germline Deisler one pathogenic variance analysis of tumor tissue from one of the children revealed to Deisler one hits mutations in Deisler. One dysregulates micro are as mimicking the effect of the activation of the chromosome nineteen micro are in a cluster. These data suggest that M H L is a new pheno type of Deisler one syndrome. Deisler one syndrome is a tumor predisposition syndrome that features several disadvantage Unedic cystic conditions in young children, most notably plural. Pulmonary blast Oma and cystic Neff froma. Chronic kidney disease of unknown cause in agricultural communities. A review article by Richard Johnson from the university of Colorado Anschutz medical campus Aurora in recent years numerous cases of chronic kidney disease have emerged among agricultural workers as well as among others performing manual labor in various regions of the world, for example, during the nineteen nineties clinicians in Central America noted that a large number of young sugar. Cane workers were presenting with end stage kidney disease and early report on an upsurge in chronic kidney disease in Central America came from El Salvador in two thousand two one striking finding was that the patients once evaluated did not have any of the conditions known to cause end stage kidney disease, spates of disease have also been identified in Sri Lanka, India and other hot reach. Regions of the world. This review describes the clinical presentation and epidemiology of chronic kidney disease, that is endemic in this workforce in these areas as well as possible causes the disease does not appear to be due to the classic causes of kidney disease such as diabetes, hypertension and glimmer healer disease. Those affected are usually men who have worked for two or more seasons are between twenty and fifty years old are ACM dramatic and have normal or only slightly elevated blood pressure and normal blood glucose levels, the disease is strongly associated with working and living in a hot environment. But whether the cause is a toxin and infectious agent a heat associated injury or a combination of factors is not yet known a forty four year old man with neck pain and swelling a case record of the Massachusetts General Hospital by Phillips sale. Taylor and colleagues a forty four year old man who's admitted to the hospital because of pain and swelling on the left side of the neck twelve weeks. Earlier the patient had undergone uncomplicated placement of an implantable cardio vertu defibrillator through the left symbolic vein. Five weeks after implantation the patient awoke with a headache and neck pain on the left side when numbness and tingling developed in the left fingertips along with shooting pains in the left arm and Toews he presented to the hospital C T and geography of the chest and abdomen revealed a partially visible mass in the left superclub akilah region. Ultrasonography of the neck revealed a complex mass measuring four point three centimetres in diameter. These findings were thought to be most consistent with a hematoma. Needle aspiration of the mass revealed five milliliters of thin Brown fluid that was suggestive of old blood three weeks after discharge the patient. Return to the emergency department for recurrent, swelling and pain in the neck ultrasonography, again revealed a heterogeneous Hypo a Kohic lesion needle aspiration was again performed and revealed one point five milliliters of thick red fluid that appear to be consistent with blood when the patient presented for the third time with the same concern. It was clear that the differential diagnosis needed to be broadened to counter possible. Heuristic errors a biopsy of the mass was performed biopsy results were most compatible with metastatic post puberty, immature territory with maturation of Mizan. Komo components. The link between Hamadeh polices and atherosclerosis a clinical implications of basic research article by Menno de vinter from the Amsterdam university medical centers, the Netherlands, the decrease in the incidence of cardiovascular disease, and the improved prognosis in persons with a diagnosis of cardiovascular disease are due in part to the development of new treatments based on a cruel of knowledge about disease mechanisms more specifically the introduction of lipid lowering therapy such as statins and PCS k nine inhibitors as well. As changes in lifestyle have reduced the risk of cardiovascular disease by an impressive twenty five to thirty percent since the nineteen sixties and nineteen seventies. However, cardiovascular disease remains a major cause of disability and death in the western world and new strategies to lower the large residual risk of cardiovascular disease are needed. There is mounting evidence. That atherosclerosis is driven. Not just by dislike -demia, but also by inflammation clinical evidence. Supporting this link includes the results of the Cana Kenya. Mab anti-inflammatory thrombosis outcomes study Cantos, which showed that targeting inflammation, improved cardiovascular outcomes. A recent study provides a molecular explanation on the basis of their studies of zebra, fish and mouse models the authors described a mechanism link between cholesterol, metabolism and inflammation, the findings revealed that pathways of tomato. Polices and cholesterol, metabolism are closely linked and control each other. Preying on prescribers and their patients pharmaceutical marketing, I- Atra, genyk, epidemics, and the Sackler legacy a perspective article by Scott Podolsky from Harvard Medical School Boston in two thousand eighteen Massachusetts joined more than two dozen other states in suing Perdue pharma, the makers of Oxycontin for the harm. They inflicted in our state by helping to drive the current opioid crisis drawing particular attention to the actions of the family that controls the company, the Sackler lers the case against Purdue has been framed in terms of unconscionable corporate and individual profit at the expense of the public's health, chiefly through the manipulation of prescribing practices and of the approach to pain recommended in clinical journals, medical curricula and professional guidelines as a Boston Globe writer, mused physicians are persuaded by Mark. Getting just like everybody else. Now, there's a discomfiting thought discomfiting as the thought may be it is not new marketings role in physician education has long been evident to pharmaceutical companies journal editors and therapeutic reformers alike, and though the Sackler family did not invent the practice of selling drugs to physicians. They were pioneers who story illustrates the ways marketers developed naturalized and monetize the interface between the pharmaceutical industry and prescribing physicians under Sackler guidance Pfizer increased, its drug Salesforce from eight detail men in nineteen fifty two two thousand by nineteen fifty seven including at one point seventy medical students. Internal memos revealed that the marketing campaigns for Tara Meyson and soon tetris in tetracycline were conducted like. Military campaigns and described in the language of combat the prey described in an internal Pfizer sales document from nineteen fifty four entitled easy prey for Tara Meyson referred not to the microbes Tara Meyson killed, but the prescribing physicians whose behavior could easily be swayed by marketing tactics. Physician participation in lethal injection a perspective article by Deborah Denno from Fordham University School of law New York on April first, the US supreme court rejected a Missouri death row inmates. Claim that executing him using the state's lethal injection protocol would violate the eighth amendment's ban on cruel and unusual punishment because blood-filled Schumer's in his head neck and throat could rupture and cause him to choke and suffer. Excruciating and prolonged pain many commentators found the five to four decision in Buccleugh V precise shocking. A stunning rebuke of eighth amendment precedent that shows divisions in the court over the use of the death penalty. Although it's difficult to predict the extent of Buckley's constitutional footprint, the opinions unusual facts and circumstances throw into sharp relief, the pervasive. Nece of physician participation in lethal injection, despite the medical communities professed condemnation of such involvement the role of doctors in all forms of execution during the past century has been thoroughly documented and in Buccleugh the court confronted a case regarding execution methods that was built almost entirely on medical input. Michael Buckley, who has congenital cavernous human Joma, the need for physician involvement in this case was clear from the start given that Buckley's challenge to the lethal injection protocol was based on a medical diagnosis yet. Buck Lou also reveals to an unprecedented degree the extent and complexity of the medical community's role in guiding and carrying out executions at baseline up perspective article by Paul burgle from the Medical College of Wisconsin, Milwaukee. This is Mr. L the resident begins yesterday, he underwent tracheostomy revision. But he developed post operative respiratory failure. He needed the ventilator overnight, but we liberated him this morning long story short he can transfer to the floor. He's back to baseline this final word reverberates in Dr Burgos mind, transmogrify ING from two innocuous syllables into an unshakable conceptual beast baseline noun won a pre existing condition requiring no further explanation a prima facial diagnosis irrelevant to immediate therapeutic goals a curiosity killer. Wait, why is it his baseline Dr Bourboule asks the resident misinterprets or cleverly sidesteps the question. He's usually on four leaders of oxygen at home. I meant why should he need a tracheostomy at all? I don't know obesity hyperventilation syndrome. He. He's had it for years, the resident eagerly divests himself of this alleged learning opportunity as the other overwork trainees grow restless, the question for many impatient. Internal medicine teams is not weather, but to what extent we should juggle treatment of patients acute health problems with care for their coexisting, chronic conditions, increasingly impatient, internal medicine teams, focus exclusively on a patient's immediate crisis leaving the rest for ambulatory care. But by adopting a baseline mindset, we are creating physicians who prioritize throughput over critical appraisal, skills and inquisitiveness. Our images in clinical medicine features. A fifty nine year old woman who presented to the emergency department with a four day history of inflammation and pain in the right eye. She had been blind in the eye for several years before presentation, the physical examination showed prop toasts of the right eye with Perry, orbital inflammation, afoul, mo- plea and to write relative Afrin pupil defect. M R I revealed. A right orbital mass measuring two point eight by two point five by two point three centimeters with intraocular and extra ocular components. Abdominal anthrax imaging showed numerous hypnotic masses. Abdominal anthrax lymphatic apathy and vertebral sclerotic Ossius disease findings that were consistent with widely metastatic disease. The right. I was in nucleated for palliative relief and to obtain tissue for diagnosis. Immuno history. Chemical evaluation supported the diagnosis of UV melanoma, the patient was treated with Bolivia MAB and Nevada MAB, but she died from progressive disease. Two months after presentation a sixty six year old man presented to the emergency department with a two month history of abdominal bloating and worsening constipation. His medical history was notable for untreated, hypertension, and hyperloop -demia. He'd been an active smoker for more than twenty years and his father had died. Suddenly at sixty two years of age from an unknown cause. The patient's blood pressure was one hundred sixty two over eighty three millimeters of mercury and the physical examination revealed. A painless pulsa total abdominal mass see the video at any J M dot org. The federal pulses were palpable on both sides CT and geography revealed a large fused form in for renewal. A Arctic aneurysm measuring eleven by ten. One point five by fourteen centimeters the patient underwent surgery during which the aneurysm was exposed and replaced with an a auto by ilyaronoff graft. He also began medical treatment for hypertension, and hyper LIPA -demia at a six month. Follow up. Visit the patient had no pulse. Atoll abdominal mass had good perfusion to his legs and felt well this concludes our summary. Let us know what you think about our audio summaries, and he comments or suggestions may be sent to audio and any J M dot org. Thank you for listening.