Perifollicular Melanocyte Regeneration in Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune skin disorder that causes fluid-filled blisters to appear on various body parts, often preceded by urticaria and pruritis. This case report describes the perifollicular melanocyte regeneration within diseased areas in a skin of color patient with BP. By reviewing the various pathologies that can result in melanocyte destruction and the basic science of melanocyte regeneration, we can better identify and explain this phenomenon to patients and lead to earlier diagnoses. Furthermore, due to the lack of published information on skin conditions in skin of color patients, this report can assist in raising awareness of an atypical BP presentation in the dermatological community.

A Modern History RAAS Inhibition and Beta Blockade for Heart Failure to Underscore the Non-equivalency of ACEIs and ARBs.

Beta blockers and renin-angiotensin-aldosterone-inhibitors (RAAS-i) including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been a mainstay of guideline-based medical therapy for heart failure with reduced ejection fraction (HFrEF) for decades. However, initial evidence supporting each of the aforenoted class of drug for heart failure indications was largely found independently of the other two classes with the exception of the addition of BBs to ACEIs. In the initial ACEI trials for HFrEF, few participants were on BBs as BBs were seen as contraindicated in HFrEF at the time. The seminal BB in HFrEF trials had high prevalence of ACEIs use as ACEIs for HF were standard of care by then, but ARBs as a class were still in their infancy. We closely examine the evidence for combinations of BB and ACEIs versus ARBs in HFrEF. In doing so, we demonstrate the lack of evidence for consideration of ARBs to be interchangeable with ACEIs when used in combination with BB and provide evidence that calls in to question the validity of assuming benefits from each drug class are independently cumulative, widening the gap between ACEIs and ARBs when used with BBs. Modern guidelines should emphasize this lack of evidence for the combination use of ARB and BB in HFrEF, except for candesartan. Even as practice moves towards the widespread uptake of angiotensin receptor-neprilysin inhibitors (which contain the ARB valsartan) in heart failure, the distinction has important implications for the ongoing role of combination therapy with BB, which thus far has been assumed, but not proven.

The significance of electrocardiographic changes without echocardiographic evidence of segmental wall motion abnormalities in patients undergoing dobutamine stress echocardiography.

Ischemic ECG changes during dobutamine stress echocardiography (DSE) have been reported to have low sensitivity and specificity for detecting myocardial ischemia in the absence of wall motion abnormalities on echocardiography. We present a case of a renal transplant candidate with severe multivessel disease who had ST depressions without any wall motion abnormalities on DSE. Certain studies have shown the sensitivity of DSE is lower in patients with left ventricular hypertrophy and/or end stage renal disease, but the significance of ischemic ECG changes with no evidence of wall motion abnormalities in these patients has not been well studied.

Risk Assessment of Stroke in Patients with Atrial Fibrillation: Current Shortcomings and Future Directions.

Atrial fibrillation is a well-known risk factor for cardioembolic stroke; a number of risk stratification scoring systems have been developed to help differentiate which patients would stand to benefit from anticoagulation. However, these scoring systems cannot be utilized in patients whose atrial fibrillation has not been diagnosed. As implantable cardiac monitors become more prevalent, it becomes possible to identify occult, subclinical atrial fibrillation. With this data, it is also possible to examine the relationship between episodes of paroxysmal atrial fibrillation and thromboembolism and the total burden of paroxysmal atrial fibrillation and thromboembolic risk. The data gleaned from these devices provides insight and raises questions regarding the underlying mechanism of thromboembolism in atrial fibrillation, and in doing so, exposes shortcomings in the present clinical use of current risk scoring systems, specifically, the inability to account for atrial fibrillation burden and to apply scores at all in subclinical atrial fibrillation.

Erectile dysfunction as a marker for cardiovascular disease diagnosis and intervention: a cost analysis.

INTRODUCTION: Erectile dysfunction (ED) is a risk factor for cardiovascular disease (CVD). We examine the costs of screening men with ED for CVD risk factors and the cost savings of treating these at risk men. AIM: This study aims to evaluate the effect of screening men presenting with ED for CVD risk factors and to determine the cost effectiveness of this screening protocol. METHODS: The known incidence and prevalence of ED and CVD, the rate of undiagnosed CVD, and the effects of CVD treatment were used to model the change in prevalence of acute CVD events and ED as a function of the number of men with ED and CVD. The cost savings associated with reduction in acute cardiovascular (CV) events and ED prevalence was estimated over 20 years. MAIN OUTCOME MEASURES: Acute CVD event rate reduction and associated cost savings were modeled over 20 years. RESULTS: The relative risk of ED in men with CVD is 1.47 and the coprevalence of both ED and CVD was estimated at 1,991,520 men. Approximately 44% of men with CVD risk factors are unaware of their risk. If all men presenting with ED were screened for CVD, 5.8 million men with previously unknown CVD risk factors would be identified over 20 years, costing $2.7 billion to screen. Assuming a 20% decrease in CV events as a result of screening and treatment, 1.1 million cardiovascular events would be avoided, saving $21.3 billion over 20 years. Similarly, 1.1 million cases of ED would be treated, saving $9.7 billion. Together, the reduction in acute CVD and ED treatment cost would save $28.5 billion over 20 years. CONCLUSIONS: Screening for CVD in men presenting with ED can be a cost-effective intervention for secondary prevention of both CVD and, over the longer term, ED.

Structural and biochemical analyses of alanine racemase from the multidrug-resistant Clostridium difficile strain 630.

Clostridium difficile, a Gram-positive, spore-forming anaerobic bacterium, is the leading cause of infectious diarrhea among hospitalized patients. C. difficile is frequently associated with antibiotic treatment, and causes diseases ranging from antibiotic-associated diarrhea to life-threatening pseudomembranous colitis. The severity of C. difficile infections is exacerbated by the emergence of hypervirulent and multidrug-resistant strains, which are difficult to treat and are often associated with increased mortality rates. Alanine racemase (Alr) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the reversible racemization of L- and D-alanine. Since D-alanine is an essential component of the bacterial cell-wall peptidoglycan, and there are no known Alr homologs in humans, this enzyme is being tested as an antibiotic target. Cycloserine is an antibiotic that inhibits Alr. In this study, the catalytic properties and crystal structures of recombinant Alr from the virulent and multidrug-resistant C. difficile strain 630 are presented. Three crystal structures of C. difficile Alr (CdAlr), corresponding to the complex with PLP, the complex with cycloserine and a K271T mutant form of the enzyme with bound PLP, are presented. The structures are prototypical Alr homodimers with two active sites in which the cofactor PLP and cycloserine are localized. Kinetic analyses reveal that the K271T mutant CdAlr has the highest catalytic constants reported to date for any Alr. Additional studies are needed to identify the basis for the high catalytic activity. The structural and activity data presented are first steps towards using CdAlr for the development of structure-based therapeutics for C. difficile infections.

Stasis dermatitis as a complication of recurrent levofloxacin-associated bilateral leg edema.

INTRODUCTION: Several drugs have been associated with the development of peripheral edema. Leg edema can result in dermatitis of the lower extremities. We describe levofloxacin-induced peripheral leg edema, which progressed to stasis dermatitis. METHODS: A 76-year-old man with a history of esophageal adenocarcinoma was administered intravenous vancomycin and a combination of piperacillin and tazobactam by injection for treatment of aspiration pneumonia. Prior to discharge, the patient's antibiotic therapy was switched to oral levofloxacin. The patient developed drug-associated bilateral peripheral leg edema and stasis dermatitis. Both the dermatitis and leg edema resolved after withdrawal of levofloxacin and administration of topical corticosteroid therapy. The patient had a similar reaction to levofloxacin one year prior, which had subsided with discontinuation of the drug. RESULTS: Several medications have been documented to cause leg edema and secondary stasis dermatitis. The timing, recurrence, and resolution of edema and stasis dermatitis with respect to the administration and termination of levofloxacin suggest that the leg edema and stasis dermatitis occurred secondary to levofloxacin administration. DISCUSSIONS: Levofloxacin can be added to the list of drugs associated with the development of peripheral leg edema. Stasis dermatitis proceeded by lower extremity edema can be added to the list of adverse events associated with levofloxacin.