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…
Assistant 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…
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…
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
2 major criteria
1 major and 2 minor
- 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)
- 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
- Lethargy or being not easily aroused from sleep
- Diastolic blood pressure >90 mmHg
- Age <5 years
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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
- 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
- Nephrotoxic and Neurotoxic
- Avoid macrolide antibiotics
- Bone marrow toxin: dose-related neutropenia
- Mycophenolate mofetil
- Mild side effect profile: abdominal pain, nausea, diarrhea, leukopenia, thrombocytopenia
- Avoid Magnesium and Aluminum antacids
- 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
- 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.
- 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
- 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
- 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.
- > 1month
- CMV, HSV (ulcers more common then vesicles)
- Fungal: Aspergillus, Candida, Cryptococcus
- Bacteria: Norcardia, Legionella, Listeria
- Increased risk of ascending cholangitis and liver abscess
- 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.
- 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
- 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.
- 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.
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