Inclusion Body Myositis 101

General information

  • Most common muscle disease in patients older than 50 years. More common in white men, but can affect any group
  • Thought to be degenerative, rather than auto-immune. Associated with systemic autoimmune or connective-tissue diseases in up to 15 %

Clinical Manifestations

  • Difficulty with everyday tasks predominantly requiring the use of proximal muscles, such as getting up from a chair, climbing steps, stepping onto a curb, lifting objects, or combing their hair
  • Fine-motor movements that depend on the strength of distal muscles (especially foot extensors and finger flexors), such as buttoning a shirt, sewing, knitting, or writing, are affected fairly early in the course
  • The pharyngeal and neck-flexor muscles are often involved, causing dysphagia or fatigue and difficulty in holding up the head
  • May also progress slowly for years, and its clinical features may simulate those of limb-girdle muscular dystrophy.
  • Consider IBM in patients with polymyositis or dermatomyositis that is resistant to treatment.

Diagnostic Criteria

  • Muscle strength – myopathic muscle weakness with early involvement of the distal muscles
  • EMG – myopathic with mixed potentials
  • Muscle enzymes – normal or elevated
  • Muscle biopsy – definitive
  • Light microscopy —  endomysial inflammation, rimmed vacoules distributed around the edge, eosinophilic cytoplasmic inclusions
  • EM — granules contain membranous whorls. Filamentous inclusions in the cytoplasm or nucleus, prominent in the vicinity of the rimmed vacuoles, are pathognomonic

Treatment

  • Inclusion-body myositis is generally resistant to all therapies, and its rate of progression also appears to be unaffected by treatment.
  • Failed therapies — Steroids, MTX, Cyclophosphamide, Beta-interferon, TNF-a inhibitors, ATGAM, IVIg
  • Future possibilities
    • Alemtuzumab, a T-cell–depleting monoclonal antibody; reported slowed disease progression, improvement of strength in some patients, and reduction in endomysial inflammation
    • Follistatin, an antagonist of the myostatin pathway, has been shown to produce a dramatic increase in muscle mass in animals
    • Arimoclomol, a heat shock protein (HSP) coinducer may slow down the process of protein misfolding and aggregation

PCSK9 Inhibitors…Closer to Approval?

This week the FDA Endocrinologic and Metabolic Drugs Advisory Committee will discuss the safety and efficacy of two PCSK9 inhibitor drugs (Praluent and Repatha) and may recommend approval of these drugs to lower cholesterol. Recently published research in NEJM showed reduced cardiovascular outcomes with these inhibitors and has sparked guarded optimism from the medical community. UT Southwestern cardiologist, Dr. Amit Khera, was recently quoted in Medscape regarding these powerful cholesterol lowering medications, “If you’re a cardiologist, you must not have a pulse if you’re not excited.” Click on the link below to read more from The Washington Post!

Could these New Cholesterol Drugs Save Many Americans from Heart Attacks?

UPDATE!

The FDA panel today recommended approval of the cholesterol drug, alirocumab, in a 13-3 vote. Click on the link below to read a summary from today’s developments from The New York Times.

Federal Panel Recommends Approving New Cholesterol Drug

Empiric Antibiotics: Septic Shock

Principles

  • Goal is “the administration of effective IV abx within 1st hour of recognition of septic shock or severe sepsis.” — (grade 1B and 1C, respectively)
  • Initial empiric Rx should include “one or more drugs active against all likely pathogens with adequate penetration into tissues presumed to be source of sepsis.” — (grade 1B)
  • Abx should be “reassessed daily for potential de-escalation.” — (grade 1B)
  • Combination therapy, when used empirically for severe sepsis, should not be continued more than 3-5 days” but de-escalate to single-agent therapy as soon as susceptibilities are known.” — (grade 2B)
  • Source control in first 12 hours if feasible. — (grade 1C)

Empiric Therapy

  • Empiric Rx depends on host factors, recent abx exposure, allergies, clinical syndrome and likely site of infection, local antibiogram and pt’s prior infections or colonization
  • Combination therapy recommended in neutropenics with severe sepsis, those with prior MDR pathogens, and respiratory failure or septic shock patients. — (grade 2B)
  • Practically, this usually means vancomycin + anti-Pseudomonal beta-lactam + either aminoglycoside or anti-Pseudomonal FQ

Picture3

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Get Fit Week! Ideal Cardiovascular Fitness

Get Fit Week

As our year comes to a close, we would like to present our last themed series of posts, a part of GET FIT WEEK. These posts will focus on the scientific evidence and guidelines for obtaining and mantaining physical fitness, with a focus on health benefits and tools for achieving these goals.

Ideal Cardiovascular Fitness

It makes sense to start with ideal cardiovascular fitness! The American Heart Association 2020 Strategic Goals include this idea. It is defined as optimal levels of three cardiovascular risk factors (blood pressure, fasting glucose, cholersterol) and 4 lifestyle behaviors (BMI, smoking, physical activity, and diet). In a cohort study of ~5800 young adults (age range of 29 to 39 years) from the United States, Finland, and Australia, investigators compared the presence of these 7 measures of ideal cardiovascular fitness with carotid intima-media thickness. The ideal numbers for each metric is as follows: BP 120/80, total cholesterol < 5.17 mmol/L, fasting glucose < 5.6 mmol/L, BMI < 25 kg/m2, and no history of smoking (or quit > 1 year ago). Ideal physical activity was defined as >150 min/week of moderate exertion or > 75 min/week of vigorous exertion. The concept of the ideal diet was most complicated, requiring 4 of the following 5 components: > 4.5 cups of fruits or vegetables per day, > two 3.5 oz servings of fish per week, > three 1 oz servings of whole grains per day, < 1500 mg sodium per day, and < 450 kcal from sugary drinks per week. One of the most notable aspects of this study was that only 1% of the participants had all 7 ideal CV health metrics! The findings of the study indicated that, with the presence of each additional “ideal” measure (i.e. well-controlled BP, recommended levels of physical activity, etc.), carotid intima-media thickness was significantly lower. Essentially, this suggests that physical fitness, as defined by the above measures of blood pressure, cholesterol, BMI, smoking, etc., not only makes you feel great, (and need less medications!), it appears to have a significant impact on the burden of atherosclerotic disease. The authors note that “this finding and the fact that complete ideal CV health was very rare among this large sample of young adults strengthen the need for early evaluation of CV risk factors and for development of effective intervention strategies for behavioral change.” The next question is, does this translate into a mortality benefit. To read the full study, click here.

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Necrotizing Fasciitis 101

General

  • Skin and soft tissue infection that extends to involve the fascia and muscles
  • Often associated with pre-existing skin infection, trauma, chronic ulcers, surgical wounds

Pathegenesis and Risk

  • Pathogens include aerobic and anaerobic bacteria including Group A Streptococcus (GAS, S. pyogenes), Clostridium perfringens, CA-MRSA, Klebsiella spp
  • Patient risk factors: Diabetes, steroids, burns, neutropenia
  • Clostridium septicum – gram positive, spore-forming anaerobe; trauma not needed for infection to occur; associated with GI and hematological malignancies
  • Clostridium causes myonecrosis through release of exotoxins
  • Clinical suspicion is important in guiding management including urgent surgical consultation – mortality ranges from 30-70% and increases with surgical delay

Management

  • Timely surgical exploration is essential to determine the extent of necrosis and debride all necrotic tissue
  • Repeat surgical exploration is typical 24-36 hours later and as needed
  • Empiric broad spectrum antibiotics should be started immediately and cover MRSA, streptococci, gram-negatives, anaerobes and narrow down pending cultures
  • Consider adding clindamycin to regimens if Group A Strep and clostridia species are suspected

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MERS Virus in South Korea Causing Concern

Recently, South Korean authorities have increased the number of people quarantined and have temporarily closed many schools due to fears of the Middle Eastern Respiratory Syndrome (MERS) spreading. As of June 4, 35 South Koreans had tested positive for the virus including 2 deaths. Click on the link below to read about this from The New York Times.

Middle Eastern Respiratory Syndrome – Coronavirus

  • Coronavirus first isolated in 2012
  • Camels and bats established as a reservoir
  • Range of disease includes “common cold” type symptoms/signs to severe pulmonary illness
  • Majority of cases identified in regions near Arabian Peninsula: Saudi Arabia, United Arab Emirates, Qatar, Oman, Jordan, Kuwait
  • Human-human spread likely requiring close-contact
  • Symptoms: fever, cough, and dypsnea most common; also includes nausea, vomiting, and diarrhea
  • Mortality: 50-65%
  • Molecular diagnostics are the method of choice: PCR assays of respiratory, stool, blood specimens
  • Treatment:
    • Cases should be reported immediately to the local and state health department
    • No antiviral therapy identified
    • Supportive care including mechanical ventilation

(Hopkins ABX Guide)

Fears of MERS Virus Prompt Broadening of Cautions in South Korea

Myocardial Infarction Complicated by Heart Block

  • Acute coronary syndrome (ACS) involves rupture or erosion of a coronary plaque with exposure of the subendothelial matrix to circulating blood and subsequent platelet adhesion, platelet activation, and platelet aggregation
  • A thrombus forms, resulting in partial or complete occlusion of the lumen of the coronary artery
  • The initial ECG is nondiagnostic in up to 50% of patients presenting with chest pain, but remains a critical part of the evaluation
  • Complete heart block (CHB) may be associated with an anterior or inferior wall MI
  • High degree AV block is associated with an increase in mortality in patients with an inferior or anterior myocardial infarction
  • Complete heart block with inferior MI generally results from an intranodal lesion and isassociated with a narrow QRS complex and develops in a progressive fashion from 1st to 2nd to 3rd degree block
  • Patients with inferior MI and CHB may be resistant to atropine and its use during active ischemia may cause ventricular fibrillation!
  • Temporary transvenous pacing is recommended
  • Patients with inferior MI and CHB typically don’t need permanent pacing as the rhythm is transient and resolves within 5-7 days

Click on the link below to see an ECG of inferior MI with complete heart block!

ECG (courtesy of Life in the Fast Lane)

Interesting Journal Articles to Read!

Today at morning report we discussed high value care and professionalism/managerial skills. We specifically noted a recent article published in JAMA by oncologist Dr. Ezekiel Emanuel from the University of Pennsylvania and an article in NEJM by Dr. Michael Porter of the Harvard Business School published in 2010. Click on the links below to read the articles!

“Higher income, higher educational attainment, and a cleaner environment are actually more important in determining patients’ well-being than health care services.” Dr. Ezekiel Emanuel

What is Value in Health Care

Enhancing Professionalism Through Management

UTSW Resident Research Featured in News!

Recently, Daniel Sullivan (PGY-01) presented research from medical school (University of Alabama) on e-cigarettes. Sullivan presented the findings at ATS this year in Denver as the findings showed higher the power of the e-cigarettes was associated with  higher concentrations of harmful subtances incluidng acetaldehyde, acrolein, and formaldehyde. The findings sparked a lot of media coverage as the use of e-cigarettes has exploded in the last few years. Check out the interview with Daniel Sullivan about this exciting research and click on the link to read the abstract from ATS Conference. Very proud of our residents!

http://www.internalmedicinenews.com/home/article/video-level-of-e-cigarette-power-contributes-to-potentially-hazardous-effects/318fc16eb3d84a0a651e7e8ed2561e53.html

Mechanical and Chemical Components of Electronic Cigarettes Affect Combustion Production Formation and Biological Pathways of Inflammation