NEJM This Week November 7, 2019
Welcome this is the New England Journal of Medicine. I'm Dr Lisa Johnson this week November seventh twenty nineteen we feature articles a neuro degenerative disease. He's informer soccer players triple treatment for cystic fibrosis. HETERO ZYGOTE S- PCI or cabbage for left main coronary disease ventilator later associated pneumonia after cardiac arrest mediators of insulin resistance and health social reform and medical schools a review article on acute severe hypertension a clinical problem solving that describes double trouble and perspective articles on the US insulin crisis on weather other emergency Holt would reduce opioid overdose deaths and on a good physician neuro degenerative disease mortality talapity among former professional soccer players by Daniel McKay from the Hamden Sports Clinic Glasgow the United Kingdom in this study death certificates were used to compare the causes of death among seven thousand six hundred seventy six former professional Scottish Soccer players and twenty three thousand twenty eight matched controls over a median of eighteen years. Fifteen point four percent end of the former soccer players and sixteen point. Five percent of the controls died. All cause mortality was lower among former players then among controls up to the age of seventy years and was higher thereafter mortality from ischemic heart disease was lower are among former players than among controls hazard ratio zero point eight as was mortality from Lung Cancer Hazard Ratio Zero Point Point five three mortality with neuro degenerative disease listed as the primary cause was one point seven percent among former soccer players wires and zero point five percent among controls among former players mortality with neurodegenerative disease listed as the primary or for a contributory cause on the death certificate varied according to disease subtype and was highest among those with Alzheimer's Disease Hazard Ratio uh-huh former players versus controls. Five point zero seven and lowest among those with Parkinson's disease hazard ratio two point one five dementia related medications were prescribed more frequently to former players then to controls odds ratio four point nine mortality with neurodegenerative disease listed as the primary or contributory cause did not differ significantly between goalkeepers and outfield players but dementia denture related. Medications were prescribed less. Frequently two goalkeepers in this retrospective epidemiologic analysis mortality from neuro degenerative generative disease was higher and mortality from other common diseases lower among former Scottish professional soccer players then among matched controls Robert Stern from Boston University. School of Medicine writes in an editorial that this study provides good news and bad news regarding the potential long-term consequences of playing soccer at the professional level. The results are similar to those from a study involving former the national football league players conducted by the Centers for Disease Control and prevention in which all cause mortality was lower among former NFL players then then in the general population but neurodegenerative mortality was higher professional. Soccer players. Do not share the body habits of American football players. There's but they do share the exposure to repetitive head impacts through routine heading of the ball and average player heads the ball six to twelve times per game in addition to heading drills at practice and thousands of times during a career in small case series studies heading has been associated with altered cerebral neuro chemistry diminished white matter integrity and quarter cle thinning in professional soccer players without obvious concussion. The new findings findings by McKay and colleagues should not engender undue fear and panic among soccer players. Parents and coaches as the authors of the current study indicate it is not possible to generalize their findings among male former professional soccer players to participants in recreational amateur or collegiate collegiate level soccer parents of children. Who headed the ball in youth or high school? Soccer should not fear that their children are destined to have cognitive decline and dementia later in life rather they should focus on the substantial health benefits from exercise and participation in a sport that their children enjoy however it is also important that the findings from the current study lead to research and increased awareness of the potential short term and long term consequences. NSA quences of heading the ball in amateur soccer perhaps however there is already adequate evidence that repeated blows to the brain from heading in professional professional. Soccer is an occupational risk that needs to be addressed Alexa Catheter. Teza Catheter Iva Catheter. After for cystic fibrosis with a single P. H. E. Five Zero Eight D. E. L. A.. Lille by Peter Middleton from the University of Sydney Westmead Need New South Wales Australia ineffective to trial involving patients who are heterosexual for the P. H. E. Five Zero Ad L. Cystic Fibrosis Trans Membrane conductors regulator cf tr mutation and minimal function mutation the next generation see FDR corrector Alexa Alexa calf door in combination with Teza Catheter and Ivankov after improved. PHP five zero ad L. C. F. T. R. Function and clinical clinical outcomes. This randomized phase. Three trial was conducted to confirm the efficacy and safety of Alexa. Catheter has occurred after Ivankov. After in four hundred three patients twelve years of age or older with cystic fibrosis with P. H. E. Five Zero Eight D. E. L. minimal function. Gino Gino Types Alexa after Teza. Catheter Ivankov after relative to placebo resulted in a percentage of predicted Efi v one. That was thirteen eighteen. Point eight points higher at four weeks and fourteen point three points. Higher through twenty four weeks a rate of pulmonary exacerbations that that was sixty three percent lower respiratory domain score on the cystic fibrosis questionnaire. Revised that was twenty point. Two points higher and sweat sweat chloride concentration. That was forty one point eight million moles per liter lower Alexa Teza Catheter. Ivankov after was generally safe and had an acceptable side effect profile. Most patients had adverse events that were mild or moderate Alexa after Teza Catheter. Ivankov after was efficacious in patients with cystic fibrosis with P. H. E. Five Zero Eight D. E. L. minimal function Gino types in whom previous previous cf tr modulator regiments were ineffective in an editorial Francis Collins from the National Institutes of Health Bethesda. Maryland writes that the results of a pair of phase three clinical trials in the journal and in a simultaneous publication. In the Lancet document and impressive benefits from triple drug therapy for persons with cystic fibrosis. And at least one copy of the P. H. E. Five Zero Away D. E. L. CF tr mutation who represent approximately ninety percent of persons affected by this life-shortening autosomal recessive disease. The these findings indicate that it may soon be possible to offer safe and effective molecular targeted therapies. To ninety percent of persons with cystic fibrosis. This should be a cause for major celebration yet. We must not abandon the patients with cystic fibrosis. Who have known mutations -tations and will not have a response to these drugs even beyond that the best day ever for all of us traveling down? This long road together will be the day. When the more than seventy thousand persons with cystic fibrosis worldwide? Do not need to take drug therapy at all. And they're finally is a permanent cure for cystic fibrosis. That works for everyone. Although the challenges are substantial one can imagine such an ultimate approach approach involving in Vivo Somatic cell gene editing of Airway epithelial cells shortly after their identification of cf tr. Thirty a years ago Dr Collins wrote a song entitled Dare to Dream. The lyrics expressed hope that the gene discovery would lead to effective treatments for cystic fibrosis. That someday we would see all our brothers and sisters breathing free. Dr Collins writes that it is profoundly. Gratifying edifying to see that this dream is coming. True Five Year outcomes after PCI or cabbage for for left main coronary disease by Greg Stone from the ICAHN School of Medicine at Mount Sinai New York long term outcomes after perky cutaneous coronary intervention. PCI with contemporary drug alluding stance as compared with coronary artery bypass grafting cabbage in patients nations. With left main coronary artery. Disease are not clearly established in this. Study one thousand nine hundred five patients with left main coronary artery disease of low or intermediate anatomical complexity were randomly assigned to undergo either. PCI with ever Alma saluting stents or cabbage at five years a primary outcome event of death stroke or myocardial. Infarction had occurred in twenty eighty two percent of the patients in the P. C. I. Group and in Nineteen Point two percent of those in the cabbage group death from any cause occurred more frequently in the P. C. I. Group then in the cabbage group in thirteen percent versus nine point nine percent in the p. c. i. and cabbage groups the incidences of definite cardiovascular death five percent and four point five percent respectively and myocardial infarction ten point six percent and nine point one percent were not significantly different. All cerebrovascular events were less frequent after p. c. i. than after cabbage. Three point three three percent versus five point two percent although the incidence of stroke was not significantly different between the two groups two point nine percent and three point seven percent send ischemia driven re vascular. Ization was more frequent after PCI sixteen point nine percent versus ten percent in patients with with left main coronary artery disease. There was no significant difference between PC. I and cabbage with respect to the rate of the composite outcome of death. Stroke or myocardial infarction at five years prevention of early ventilator associated pneumonia after cardiac arrest by blue no hosoi from Johnny Mass Young polyvalent Limaj France patients treated with targeted temperature management thirty to thirty four degrees Celsius after cardiac arrest are at increased risk for early ventilator associated. Pneumonia this is trial involved. One hundred ninety four adult patients in intensive care units who were being mechanically ventilated after out of hospital. Cardiac arrest related the two initial shock. -able rhythm and treated with targeted temperature management at thirty two to thirty four degrees Celsius. Either Intravenous Amoxicillin Ceiling Clavier Linate or Placebo was administered three times a day for two days starting less than six hours after the cardiac arrest the incidents it inside of early ventilator associated. Pneumonia was lower with antibiotic prophylaxis than with Placebo. Nineteen percent of patients versus thirty. Thirty four percent no significant between group differences were observed for other key clinical variables such as ventilator free days and mortality at day. Twenty eight at day seven. No increase in resistant. Bacteria was identified serious adverse events did not differ significantly between the two groups. A two day course of antibiotic therapy with Amoxicillin Clavier Linate in patients receiving a thirty two to thirty four degrees Celsius Targeted temperature management strategy. After out of hospital cardiac arrest with initial shock -able rhythm resulted in a lower incidence of early aleve ventilator associated pneumonia than placebo acute severe hypertension a clinical practice article by Aldo Aldo. Push Oto from Yale School of Medicine New Haven Connecticut. Blood pressure elevations. Above one hundred eighty over one hundred ten to one one hundred twenty millimeters mercury can result in acute injury to the heart brain and the micro vascular if acute hypertension mediated target. Arket organ damage is present. The condition is labeled hypertensive emergency and demands immediate and aggressive treatment to limit progressive injury. A hypertensive emergency is associated with substantial morbidity and in hospital mortality acute severe hypertension without acute target target organ damage. Hypertensive urgency is not associated with adverse short term outcomes and can be managed in the ambulatory setting non adherence to previously prescribed. Anti hypertensive. Medications is the most common factor leading to acute severe hypertension chronic hypertension engine shifts the cerebral blood flow auto regulation curve to the right. That is to hire blood pressure levels which confers a predisposition to cerebral cerebral hypo perfusion at relatively high normal blood pressure levels. This principle guides the pace of blood pressure reduction in acute severe severe hypertension hypertensive emergencies are managed with intravenous medications guided by the type of target organ damage. Hypertensive emergencies should be managed with oral medications and arrangements for prompted. Follow up listen to the full text of this article at any. AM DOT ORG double trouble. A clinical problem solving article by Christopher Smith from the Veterans Affairs. Ann Arbor medical all center Michigan a fifty one year old man presented with a four week history of cough associated with fever chills fatigue and aching living in the joints. The cough was initially productive of blood tinged flim but later became dry an x ray of the chest showed a no passively at the right cardio frantic angle but no plural of fusion. His condition did not improve after. Two courses of macrolide antibiotic therapy one month later. His wife brought him to the emergency department where he reported severe weakness Fatigue and frequent muscle spasms his wife noted that he seemed confused. His examination was unchanged from his previous outpatient visit except that he appeared lethargic had mild tenderness over the right anterior anterior chest wall and had asterix's C. T. of the chest revealed small right pleural of fusion. The patient produced no urine despite fight placement of an end. Welling you re throw catheter. And Maria is caused by severe intra-regional injury or complete urinary obstruction obstruction. The most direct test to elucidate the cause of the patient's pulmonary and renal disease would be renal biopsy a biopsy specimen of the kidney showed severe Calamari lightest on light microscopy ancillary testing showed markedly positive anti-proteinase three and anti GBM am antibody levels that indicated a dual positive auto immune phenotype Gla Mario nephritis with coexistent Anka's and anti GBM. Antibodies double antibody positive. Disease was diagnosed non Alcoholic Fatty Liver Disease Insulin resistance and Serra minds a clinical implications of basic research article by Varman Samuel from Yale School of Medicine newhaven insulin resistance is present in most but not all obese and elderly patients and even some young and lean persons it is a precursor cursor to and accelerate of coexisting conditions such as type two diabetes. atherosclerosis non alcoholic fatty liver disease and probably obesity obesity associated cancers. There is broad consensus. That insulin resistance is associated with ectopic lipid deposition in skeletal muscle and liver. However multiple lipid species are implicated and the molecular mechanisms? Impairing the action of insulin are debated in one model an the increase in. SSN One to dice glycerin all impairs insulin signaling. In addition a substantial body of work supports a role for ceremonies in promoting insulin resistance serum needs. Like the dyson Glycerin calls are bioactive lipid intermediates a recent study established. The importance of absurd reminds through the genetic manipulation of Di Hydro Serum I D- saturates. One does one in mice. The recent study implicates locates elevated levels of serum. I'd and their effect. I might owe conrail function in the mediation of cellular insulin resistance the health social reform and medical schools the training of American physicians and the dissenting tradition a medicine society article by Merlin Chow Kwanyan from Columbia University. New York medical schools. Continue to admit low numbers of black and Hispanic students groups that accounted for only five point seven percent in four point six percent respectively of twenty fifteen graduating classes and many medical schools continue to score low on standardized indexes gauging commitment to a broader social mission measured by percentages of graduates. It's who pursue primary care or work in medically underserved geographic areas. What can be done to address these deficits medical schools schools throughout the country? Have hosted white coat Diane's in solidarity with National Movements Against Racism and police brutality medical students the public defended the affordable care act as it faced new political threats most recently an ad hoc group called scrubs addressing. The firearm epidemic convened campus actions. That framed gun violence as an urgent health problem but this activist revival can also be the understood from a longer term perspective in the context of a dissenting tradition in. US medical training. Though never in the mainstream trainee the activists have repeatedly reimagined what the profession could be at. Its best these authors focus on curricular reform expanded did community outreach and the fight against racial exclusion as lead by two little known but influential organizations. The Association of of interns and medical students aims and the Student Health Organizations S. H. O. The US insulin crisis rationing a life saving medication discovered in the nineteen twenties. A Perspective article by Michael Froehlich from Mount Sinai Hospital Toronto on January Twenty Third Nineteen twenty. Two Insulin was successfully injected into a fourteen year. Old Boy with with severe type. One diabetes melodies type one diabetes had been considered a universally fatal disease for their discovery of insulin. Insulin Frederick Banting. And John Macleod were awarded the Nineteen twenty-three Nobel Prize in physiology or medicine. The members of their team sold the patent for insulin to the University of Toronto for one dollar each banting famously stated insulin does not belong to me. It belongs to the world immediately. After Insulin's discovery patients flocked to Toronto for what was being referred to as a Miracle Substance Indi- demand was strong but the supply was limited which led to the initial rationing of insulin in one thousand. Nine hundred twenty three before it was successfully mass produced by. Eli Eli Lilly. And the company that later became Novo Nordisk the price of one hundred units of regular short acting. Insulin was about one dollar in. US US dollars during this period and fell to less than twenty cents in the nineteen forties as manufacturing processes improved over the past two decades cades however the price of insulin in the United States has risen substantially and is now inaccessible to thousands of Americans because of its high cost. The rising costs can be attributed primarily to two phenomena first. US law allows pharmaceutical manufacturers factual errors to price their products at whatever level. They believe the market will bear and to raise prices over time without limit. Second Direct direct competition in the insulin market is lacking will emergency holds reduce OPIOID overdose deaths perspective article by Elizabeth Samuels from Warren Alpert Medical School at Brown University. Providence Rhode Island as part of efforts to reduce deuce overdose deaths and increase enrollment in treatment. Lawmakers in some states are contemplating an acting or expanding emergency hold laws that that permits some patients with severe substance use disorder to be involuntarily detained for short-term observation and in some cases treatment a bill introduced in Rhode Island during the past two legislative sessions. For example would allow physicians to request that a court order a seventy two hour hold for inpatient nation treatment for a person with substance use disorder who presents a danger or threat of danger to self family or others if not treated similar statutes have already been enacted in other states including Minnesota and Washington. Emergency hold laws are modeled. After and often extensions of existing testing measures that permit short term evaluation and treatment of people in mental health crisis using short-term emergency holds in the context of opioid use use disorder presumes that a person's risk of overdose will be mitigated by a brief involuntary hospitalization but the efficacy of emergency holds for substance use. Disorders hasn't been evaluated their use in this context raises ethical legal medical and practical questions that merit careful consideration consideration given the profound effects that holds would have an individual liberty relationships between patients and physicians and the healthcare delivery system them a good physician on complacency and communication a perspective article by Michelle Kitson from the cedars-sinai Medical Center Los Angeles Dr Kitson recently cared for a forty five year old man for over a month and never spoke to him. The patient patient was admitted with Cardio. GENYK shock stabilized and listed for heart transplantation every morning Dr Kilson rounded with her heart failure team. The patient pulmonary artery catheter secured to his neck usually looked up when they entered but then returned his attention immediately to his phone as Dr Kilson spoke to his father. She glanced at her patient. She never knew how much he understood or what he was thinking. After a few months the patient received the magic call aw he sailed through. Transplantation was home within ten days. Dr Kitson should have been proud but an adage from William Ostler nagged at her. The the good physician treats the disease. The great physician treats the patient. WHO has the disease? She knew she had missed the mark. When presented did with the unique challenge of caring for a deaf patient? She took the convenient way out every day for a month half the problem was logistics scheduling a daily real-life asl. Interpreters seemed impossible. The other half was the absurdity of video interpreter. In retrospect she should have used the patient's father as interpreter instead of Messenger but on her first day neither the patient nor his father requested that she speak directly with the patient and after the Second Linden third days past with the same calm acceptance they fell into an easy for Dr kitson inertia. She had failed to comfort a patient in need and she'd missed out on the joy of that relationship are images in clinical medicine features a fifty two year old man who presented to the outpatient clinic with with a bleeding mass on his right great toe. Two months earlier the patient had noticed a pink nargile that was approximately five millimeters in diameter on the door. Some of the to- one month later. His Toe was stepped on after which the Najran grew rapidly and bled intermittently on examination. The lesion was read head and also rated with surrounding hyper pigmentation. He was referred for surgical reception during Surgery Brown. Black Patches were found on the bottom of the mass his logic analysis of both the respected mass and the patch underneath. It showed nests of melanoma cells a diagnosis of acro link. Melanoma with invasion of the reticulation Durmus was made extended section of the lesion and skin grafting were performed the result of sentinel lymph node. Biopsy was negative. The patient received treatment with Interferon Alpha Two B. After surgery at the eighteen month the follow up there was no evidence of recurrence or metastases. A forty year old man presented to the emergency department with fatigue that it had progressively worsened over a period of three months. He had recently emigrated from Mexico where he had worked on a farm and eaten raw watercress laboratory. Laboratory studies showed severe anemia. An alkyl phosphates level of three hundred forty two units per leader and an absolute. Es Nfl Count of one. One thousand four hundred cells per cubic millimetre ultrasonography of the abdomen. Revealed Intra hypnotic Bill Eerie. Ductile Dila tation and Mr Colangelo NGO pancreatitis graffiti revealed a Hyler stricture endoscopic retrograde. Colegio pancreatitis. Griffey was then performed and large flat. Worms arms were visualized emerging from the major Waddell. Pilla see the video at any J. M. Dot org worms were extracted and identified as has the Common Liver Fluke. Fascia Sola have Hadaka Fanciulla eggs. In the feces of host animals commonly sheep contaminate fresh water the larvae mature in snails and attached to vegetation after the parasites are ingested by humans. They penetrate the intestine and invade the hip pat obituary tree after treatment with blood transfusion and try Klabin dissolved.