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"The Viral Hypothesis of Alzheimer's Disease: Time to put it to the test!" by Steven P. LaRosa, M.D.

Alzheimer’s disease (AD) was estimated to affect 35.5 million people worldwide in 2010 and is expected to affect 115.4 million people by 2050. Approximately 10% of people over 65 are affected and 50% of population > 85 are affected. The currently approved drugs provide minimal benefit. The benefit of experimental drugs observed in Phase II clinical trials has been followed by resounding failures in adequately powered Phase III clinical trials. Even the results of the highly publicized Biogen study have significant questions associated with it. It is quite clear that a new strategy must be entertained and tested.
Four members of the Human Herpes Virus family have been associated with development of Alzheimer’s disease; HSV-1, VZV, HHV-6A, and HHV-7. HSV-1 is capable in vitro leading to the production the Beta amyloid protein found in senile plaques and phosphorylating tau protein seen in neurofibrillary tangles seen in Alzheimer’s, a phenomenon that can be blocked by co-incubating …
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“The State of Sepsis and Alzheimer’s Disease Research: Birds of a Feather” by Steven P. LaRosa, M.D.

I have spent the greater part of 20 years as a clinical trialist is sepsis. Recently I have become interested as an Infectious Disease Physician in the viral disease of Alzheimer’s disease. What has amazed me is how similar the situation is in both fields. Both illnesses afflict affect millions worldwide with the annual incidence growing rapidly as the population ages. Despite improvements in background care, the one month mortality from sepsis remains high at 20%. There are no adjuvant agents FDA approved to reverse the organ dysfunction seen in sepsis. The prognosis in those afflicted with Alzheimer’s disease is also poor, and currently FDA-approved therapies amount to what my colleague states as “giving the patient a cup of coffee”.
The history of clinical trials in the two disease entities is also remarkably similar. Thousands of patients and millions of dollars have been spent on clinical trials of experimental therapies. These two diseases are the “holy grails” or “Moby Dicks”…

"EBV: The red haired stepchild that we should pay attention to!" by Steven P. LaRosa,M.D.

Epstein -Barr Virus (EBV), a member of the Herpes Virus family is often overlooked compared to its cousins HSV-1, HSV-2, VZV and CMV. As an Infectious Disease physician I suspect that this is in part due a taint that goes back to the days of patients complaining that they had "Chronic EBV" or chronic fatigue due to EBV (neither of which was true). Additionally, the currently available anti-virals Acyclovir, Valacyclovir, Ganciclovir and Valganciclovir have not demonstrated clinical improvement in patients with EBV infection. EBV infects approximately 90 % of people during their lifetime. Approximately 30-40% of people infected will develop acute infectious mononucleosis (IM).The annual rate of IM in college students and military recruits is 1-5%. This is characterized by high fevers, lymphadenopathy, exudative pharyngitis, transaminitis, and splenomegaly. While acute IM from EBV is not associated with significant mortality  it is associated with a significant morbidity. Tho…

"Getting Serious About Vancomycin Selection and Dosing" by Steven P. LaRosa, M.D.

Introduction As an Infectious Disease physician and Antimicrobial Stewardship Director I encounter a large number of patients who have been empirically started on Vancomycin due to a concern for MRSA infections or Gram positive infection with a reported penicillin allergy. I often see patients being given 1gm IV q 12hours without any attention to seriousness of illness, body weight, kidney function or susceptibility of the infecting organism. This blog will address how to optimize the use and dosing of Vancomycin.

Is Vancomycin even necessary? Vancomycin is quite often given as part of empiric therapy for pneumonia and skin and soft tissue infections without much thought as to if it is necessary. A good starting point in the evaluation of the need for Vancomycin is to a "chart biopsy" on the patient. In the evaluation of the EMR I look for past cultures or MRSA screen results. This exercise may reveal that the patient has had in fact MSSA and not MRSA colonization/infections (s…

"Let's Increase the Use of Tetracyclines to Decrease C. difficile colitis" by Steven P. LaRosa, M.D.

Physicians are quite comfortable with the use of the tetracycline antibiotics Doxycycline and Minocycline in tickborne infections and acne. Short of these two indications this class of antibiotics is rarely reached for. A new study by Raseen Tariq and colleagues in Clinical Infectious Disease 2018;66(4):514-522 should change that. A meta-analysis of 6 studies demonstrated that tetracyclines were associated with a decreased risk of C diff Infection (CDI) (odds ratio 0.62, 95% CI , 0.40-0.81; p < .001. This decreased risk held when just Doxycycline was examined. There are at least 2 potential biologic explanations for this observed effect. The first is that tetracycyclines cause fewer and shorter lasting perturbations to the fecal microbiota than other classes of antibiotics. The second is that enteral delivery of tetracyclines has inhibitory effect on Clostridium difficile. In fact, Tigecycline, a glyclcycline relative of tetracyclines, has been used successfully as a salvage ther…

"Time to Reanimate Il-1ra for Sepsis" by Steven P. LaRosa, M.D.

My introduction to the world of clinical trials in sepsis occurred in the 1990’s while I was an Internal Medicine Resident in the MICU at the Cleveland Clinic. My attending physician and ICU director, Charles J. Fisher, Jr, was the lead investigator for the Phase III trial of Interleukin-1 receptor antagonist (IL-1 ra) in patients with sepsis. The basis of the strategy related to the discovery by Charles Dinarello, M.D. of IL-1 and the role it played in the pathophysiology of febrile vasodilatory shock. During this rotation I had the opportunity to enroll a patient of mine into this trial. He was a previously healthy 28 year old male who perforated his bowel as an initial presentation of inflammatory bowel disease. At the time of enrollment the patient was maxed out on vasopressors for septic shock, in ARDS, DIC and acute renal failure. Within 24 hours of beginning the study drug infusion the patient had a miraculous improvement and ultimately survived. When the study blind was broke…