Online Tool from Johns Hopkins Visualizes Ebola’s Proteins to Help Find Cure

ebola 3d Online Tool from Johns Hopkins Visualizes Ebolas Proteins to Help Find Cure

Researchers around the world are understandably working in haste to come up with a treatment for the Ebola infection. To help with that goal, a team of scientists at Johns Hopkins University just unveiled a free online tool that helps to visualize Ebola gene mutations and how they affect the virus’s protein structure, as well as epitopes, binding sites on the surface of the proteins.

The tool is called MuPIT (Mutation Position Imaging Toolkit) and you can play around with it here. Using it, researchers should have a better idea of what mutations to expect and potentially create drugs and vaccines that target those mutations.

Some details about the tool and what led to its development according to a Johns Hopkins press release:

Karchin’s team designed its new digital display tool to connect with the new Ebola Genome Browser released recently by the University of California, Santa Cruz. The UCSC browser offers detailed genetic information about the virus. The Johns Hopkins add-on provides 3-D views of Ebola’s proteins, making it easier to interpret the functional implications of mutations and their relationship to Ebola virus evolution and its potential vulnerabilities.

The Karchin Lab’s MuPIT Ebola Edition software was devised in response to a request from UCSC Cruz bioinformatics researcher David Haussler, who was one of Karchin’s graduate faculty advisers.

This first edition of MuPIT Ebola provides visualization of user-specified mutations as well as mutations from 101 viral genome sequences, derived from blood samples taken from Ebola patients in West Africa. It includes functional annotations from the Universal Protein Resource database and epitope sequences from the Immune Epitope and Analysis Resource.

Link: MuPIT Ebola Edition…

JHU: New Online 3-D Tool Seeks Possible Targets To Disable Ebola Virus…

Robotic Walker for Improved Rehabilitation

novelrobotic Robotic Walker for Improved RehabilitationAssistant Professor Yu Haoyong and his team from the National University of Singapore have created a robotic walker to assist physiotherapists. This newly designed device promises not only to improve the quality but also the productivity of therapy sessions. The most important aspect of this machine is that it allows the patient to practice walking on the ground instead of a treadmill.

This technology consists of six different modules: an active body weight support unit; an omni-directional mobile platform; a pelvic and trunk motion support unit; a functional electrical stimulator; a variety of body sensors, and an easy-to-understand user interface.

The body sensors provide feedback on the patient’s gait to the robot so it can adjust the amount of support to help the patient walk more normally. The electrical stimulation component allows the delivery of electrical current to spur leg muscles to move. Furthermore, the robotic walker can provide tunable forces to assist, resist, or disturb the patient’s walk, which allows the therapist to set specific training schemes and relieve him/herself of any physical labor that would otherwise be necessary to support the patient.

Assistant Professor Yu is already planning clinical studies at the National University Hospital and later plans to commercialize the product for use in outpatient clinics and rehabilitation centers.

National University of Singapore Press Release: Novel robotic walker invented by NUS researchers…

Grayhill 17 Megapixel Touch Panels for Medical Applications

grayhill Grayhill 17 Megapixel Touch Panels for Medical Applications layers Grayhill 17 Megapixel Touch Panels for Medical Applications

Grayhll (La Grange, IL), a company that makes all sorts of human interface devices, is releasing new high resolution touch panels for medical applications. The screens are able to track up to ten fingers at 4,096 x 4,096 (17 megapixel) accuracy. Plus, they work just fine with medical gloves, and since the screens can be disinfected, they can be used in surgical applications for radiological image browsing, accessing patient data, and as an interface to other equipment in the OR.

The screens actually recognize that the user is wearing gloves and adjust accordingly. Moreover, if liquid hits the screen, it knows that too and automatically engages the so called “Fluid Compatibility Mode” so you can feel like you’re an officer under Captain Kirk’s command as you navigate through the patient’s PACS data.

Grayhill developed its own optical bonding technology that creates a perfect seal between the layers of the panel, pretty much guaranteeing that moisture, dust, and bacteria can’t get in. They’ll be at the upcoming RSNA conference in Chicago starting later this week.

Grayhill: NEW INSTINCT TOUCH PANELS PREVIEWED AT RSNA…

Assessing for cerebral edema in DKA

Adapted from Muir et al, Diabetes Care, 2004 here is a protocol/schema that can guide in the assessment of cerebral edema in DKA. Recall that the symptoms of cerebral edema vary, and it can be especially difficult to diagnose as findings will occur ahead of CT/MRi changes. One-half to 1% of patients in DKA have cerebral edema, the mortality of which approaches 20%. The authors noted that in their small sample it was 92% specific and 96% sensitive.

You should use this tool only after therapy (insulin/fluids) has begun. You should suspect cerebral edema if:

Any diagnostic criteria
   OR
2 major criteria
   OR
1 major and 2 minor

Diagnostic criteria

  • Abnormal motor or verbal response to pain
  • Decorticate or decerebrate posture
  • Cranial nerve palsy (especially III, IV, and VI)
  • Abnormal neurogenic respiratory pattern (eg, grunting, tachypnea, Cheyne-Stokes, apneusis)

Major criteria

  • Altered mentation/fluctuating level of consciousness
  • Sustained heart rate deceleration (≥ 20 beats per minute) not attributable to improved intravascular volume or sleep state
  • Age-inappropriate incontinence

Minor criteria

  • Vomiting
  • Headache
  • Lethargy or being not easily aroused from sleep
  • Diastolic blood pressure >90 mmHg
  • Age <5 years

The post Assessing for cerebral edema in DKA appeared first on PEM Blog.

Power Review: Transplant Patient Management

Author: Amar Patel, MD (Resident Physician – EM, Penn State Hershey Medical Center) // Editor: Alex Koyfman, MD & Justin Bright, MD

  • General Information
    • Solid organ transplant patients presenting to the ED have complications that come in 4 varieties: anatomic, infection, rejection, drug toxicity. The most common of these being infection.

 

  • Infection Time Table
    • <1 month
      • Related to surgery, stents, catheters, intubations
      • Hospital-acquired infections prominent: full immunosuppression has not peaked
      • Organisms and treatment same as for any immunocompromised patient
        • MRSA, VRE, Candida species

 

  • 1 to 6 months
    • Cytomegalovirus (CMV)
      • Most common and affects multiple systems; usually pneumonitis
      • Can trigger rejection
      • May need bronchoalveolar lavage or biopsy to diagnose
      • Check for chorioretinitis: indicates a poor prognosis
      • Treatment: Ganciclovir or Immunoglobulin
    • Ebstein-Barr Virus (EBV)
      • Similar effects as CMV clinically
      • Can trigger rejection
      • B cell lymphoproliferative syndrome
    • Human Herpes Virus 6 (HHV-6)
      • BM suppression, pneumonia, encephalitis
    • Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), BK polyomavirus
    • Opportunistic infections: Pneumocystis, Listeria, Fungal species

 

  • >6 months
    • 3 groups for susceptibility
      • Healthy Transplant Patient: low-dose immunosuppression with slightly increased risk of community-acquired infections
      • Chronical Viral Infection Patient: progressive disease process (hepatocellular carcinoma or B-cell lymphoma via viral etiologies) or recurrent exacerbations of Varicella Zoster Virus and Herpes Simplex Virus
      • Chronic Rejection Patient: aggressive immunosuppression; patients are very susceptible to opportunistic infections

 

  • Drug toxicity of immunosuppression
    • Cyclosporine
      • Nephrotoxicity: dose-related
        • Adjust medication dosages for renal toxicity and check drug level before adding new medications
        • May cause renal artery vasospasm: treat HTN aggressively
      • May cause Gout

 

  • Tacrolimus
    • Nephrotoxic and Neurotoxic
    • Avoid macrolide antibiotics

 

  • Azathioprine
    • Bone marrow toxin: dose-related neutropenia

 

  • Mycophenolate mofetil
    • Mild side effect profile: abdominal pain, nausea, diarrhea, leukopenia, thrombocytopenia
    • Avoid Magnesium and Aluminum antacids

 

  • Corticosteroids
    • Long list including not limited to: osteoporosis, cataracts, GI bleeding, adrenal suppression, glucose intolerance, AMS

 

  • Management of Specific Organ: all of the following should include basic labs, as well as, cultures including viral and fungal dependent on suspicion. Always contact transplant center! It is vital to know the new anatomy of the patient as well as medication regimen. Remember in the acute situation that rejection will not kill the patient but infection will; thus, important to manage infection and rule it out before initiation of rejection treatment which will normally be started by transplant center. In patients >1 year post-transplant, cancer should be on the differential; most commonly hepatocellular carcinoma, squamous cell carcinoma, and lymphoma.

 

  • Key Historical Inquires
    • Recent temperature changes
    • Any changes from baseline
    • Rejection History
    • Date of Transplant and Center
    • Medication changes
    • Immunization history
    • Chronic infections
    • Compliance to medications

 

  • Heart
    • General: 60% of heart transplant patients presenting to the ED will be admitted. These patients will not have chest pain due to denervation and will have signs of CHF as an indication of ischemic disease as well as rejection. Stress can still increase heart rate and exogenous pressors will work as well as anti-hypertensive medications but atropine will not. Normal HR for these patients is between 90-100 and the EKG will show 2 distinct P waves, this is not 2nd degree heart block.

 

  • Infection
    • Be aggressive with looking for source of fever.
      • Blood and urine cultures, +/-CT, +/-LP, +/-bronchoscopy, ECG, bedside TTE, basic labs
    • If your patient is septic and requires fluid resuscitation, don’t be timid
    • Most common skin infection will be herpes zoster
    • Nausea, vomiting, diarrhea: think CMV
    • Headache, fever, AMS, seizure
      • Cover for Listeria, Cryptococcal meningitis, Toxoplasma gondii, Norcardia, and Aspergillosis

 

  • Rejection
    • Signs of CHF, dysrhythmias, decreased QRS voltage, new S3
    • Contact transplant center for treatment protocol for acute rejection but generally involves increased dose of steroids and OKT3

 

  • Liver
    • General: most common vascular complication is hepatic artery thrombosis which will occur early after transplant so every patient presenting with dysfunction to the ED should get a formal ultrasound. Bile leaks and strictures are seen later and typically present with RUQ pain and elevated liver enzymes.

 

  • Infection
    • > 1month
      • CMV, HSV (ulcers more common then vesicles)
      • Fungal: Aspergillus, Candida, Cryptococcus
      • Protozoan
      • Bacteria: Norcardia, Legionella, Listeria
    • Increased risk of ascending cholangitis and liver abscess

 

  • Kidney
    • General: the kidney is transplanted in the retroperitoneal area of the anterior pelvis; most common and successful of all transplants. Basic labs should always be done paying special attention to Cr as well as cyclosporine and tacrolimus levels since both drugs are nephrotoxic.

 

  • Infection
    • Pyelonephritis
      • 35% in 1st 4 months
    • HCV most common cause of hepatitis in renal transplant patients
      • Not seen till after 4 months
      • These patients have an increased risk of spontaneous bacterial peritonitis

 

  • Rejection
    • Present with fever, LE swelling, tenderness over graft, HTN, and decreased urine output
    • Subtle rise in Cr of >20% from baseline is a sign of rejection
    • Prompt renal ultrasound and nephrology/transplant consult.

 

  • Summary
    • The transplant patient is always sicker than they appear. It is important to be aggressive in these patients since they are severely immunocompromised which not only puts them at greater risk of infection but also blunts their normal signs to infection. Always contact the transplant team to help with management as many centers have specific protocols for treatment of rejection and infection. Often it is very difficult to differentiate between rejection and infection. In these cases, treat on the side of infection as it would be the greatest immediate threat to life in the patient.

 

  • References / Further Reading

-Marx JA, Hockberger RS, Walls RM. Rosen’s Emergency Medicine, Eighth Edition. 2014; 184: 2368-2377.
-Cline DM, Ma OJ, Cydulka RK, Meckler GD, Handel DA, Thomas SH. Tintinalli’s Emergency Medicine, Seventh Edition. 2012; ch295.
-http://www.ncbi.nlm.nih.gov/pubmed/25219330
-http://www.ncbi.nlm.nih.gov/pubmed/25018848
-http://www.ncbi.nlm.nih.gov/pubmed/24994691
-http://www.ncbi.nlm.nih.gov/pubmed/22582476
-http://www.ncbi.nlm.nih.gov/pubmed/19931790
-http://www.ncbi.nlm.nih.gov/pubmed/10958130
-http://www.ncbi.nlm.nih.gov/pubmed/22678945

 

The post Power Review: Transplant Patient Management appeared first on emDocs.

A Brave New Kayexalate Free World

A guest post by Rory Spiegel (@EMNerd_) who blogs on nihilism and the art of doing nothing at emnerd.com.

There may soon come a time when we witness the death of the much maligned cation-exchange resin, Kayexalate  Unfortunately not for the reasons we hoped. We will not see the use of sodium polystyrene sulfonate fade from use in the modern Emergency Department because of our tireless efforts to remind our Internal Medicine colleagues of its lack of efficacy. Rather its clinically irrelevant place in the management of acute hyperkalemia will now be replaced by a brand new shiny cation-exchange resin that our Nephrologist consultants can use to delay the 3 am dialysis treatment our patient with a potassium of 9 mmol/L desperately requires.

Enter sodium zirconium cyclosilicate (ZS-9), a highly selective cation-exchanger that entraps potassium in the intestinal tract in exchange for sodium and hydrogen. Makers of this medication, ZS Pharma, claim it entraps 10 times as much potassium as the tried and (not-so-)true Kayexalate  A recent article published in the NEJM examines its efficacy in patients presenting with hyperkalemia. Authors, Packham et al, randomized 753 patients presenting with mild hyperkalemia (5.0 to 6.5 mmol/L) to either 1.25g, 2.5g, 5g, 10g, or placebo every 8 hours for 48 hours. Only the patients who responded to ZS-9 during the initial phase and were normokalemic after 48 hours were then randomized to either once daily ZS-9 at the original dose they were randomized to or placebo.  Unfortunately none of the patients who truly concern us were included in this trial. Authors excluded patients if they were receiving dialysis, had diabetic ketoacidosis, had a potassium level of more than 6.5 mmol/L, or a cardiac arrhythmia that required immediate treatment. These are often the patients in which we are asked to perform a trial of Kayexalate therapy in place of definitive dialysis.

For the initial phase of the trial, the authors found a statistically significant difference in their primary endpoint, the between-group difference in the exponential rate of change in the mean serum potassium level during the first 48 hours of treatment, between patients receiving the 2.5g, 5g, and 10g dose when compared to placebo.  At 48 hours, the absolute mean reductions in the 2.5g, 5g, and 10g group were 0.46 mmol/L, 0.54 mmol/L, and 0.73 mmol/L respectively. These differences were statistically significant when compared with a mean reduction of 0.25 mmol/L that was seen in the placebo group. The overall reduction in potassium seemed to be mildly correlated with the extent of hyperkalemia at presentation, but authors only presented the results of this analysis in the group who was administered the 10g dose of ZS-9 (1.1 mmol/L > 5.5 mmol/L, 1.0 mmol/L 5.4 to 5.5 mmol/L, and 0.6 mmol/L < 5.3 mmol/L or less). Additionally patients who received the 5g and 10g doses of ZS-9 during the 15-day maintenance phase, had significantly fewer repeat episodes of hyperkalemia. A second study just published in JAMA by Kosiborod et al also examining the utility of ZS-9 in the acute management of mild hyperkalemia (5.0 to 6.5 mmol/L) confirms these findings. Though in this trial, patients in the first 48 hours were not randomized, but rather all were given a 10g dose every 8 hours, the mean absolute change in serum potassium was comparable to the change observed in the 10g group in the Packham et al trial( −0.7 mmol/L at 24 hours and −1.1 mmol/L at 48 hours). Likewise the severity dependent response was also observed in this second trial.

Although statistically a success, ZS-9 adds very little to the acute management of clinically relevant hyperkalemia. Even the high doses of ZS-9 reduced the potassium level on average by 0.73 mmol/L at 48-hours, nowhere near the efficacy that would allow us to comfortably hold dialysis overnight in the acutely hyperkalemic patient. Interestingly these results are not dissimilar to what Scherr et al discovered in their 1961 investigation into the effects of Kayexalate on serum potassium. In this non-randomized, non-blinded trial the cation-exchange resin lowered patients potassium by a mean of 1.0 mmol/L over the first 24-hours.  Furthermore unlike the Scherr cohort neither of these studies examined oliguric patients or those with a history of ESRD on dialysis. The very patients which most frequently require emergent dialysis for acutely elevated levels of serum potassium.

Neither of these trials possessed the statistical power to definitively assess safety. Though no obvious concerns were demonstrated in this cohort, the rates of intestinal necrosis observed in patients given Kayexalate are far too infrequent to detect if ZS-9 causes similar effects with such a small sample size. While none of the patients in either of these trial experienced a fatal arrhythmia related to their hyperkalemia, the authors’ inclusion and exclusion criteria insured these types of events would be highly unlikely. On a side note, ED nurses will be happy to see that rate of diarrhea following the administration of ZS-9 at 1.9% is far less than what is commonly seen in patients given Kayexalate.

The editorial published alongside the Packham et al paper in the NEJM is entitled, “A New Era in the Management of Hypoerkalemia”. Though ZS-9 may play a role in the long-term management of patients at risk for hyperkalemia, for the acute management of hyperkalemia it seems we will still be arguing with our consultants over the administration of an ineffective exchange resin as a replacement for the definitive dialysis they require. A new era indeed…

"Sodium Zirconium Cyclosilicate in Hyperkalemia" http://www.nejm.org/doi/full/10.1056/NEJMoa1411487

"Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia The HARMONIZE Randomized Clinical Trial" http://jama.jamanetwork.com/article.aspx?articleid=1936753