Testosterone replacement in men with low T

Bone mineral density and bone strength improved, but we need to find out about fracture risk.

Leprosy review

Free full text.

Laboratory diagnosis of Legionnaires’ disease

From a recent review:

Legionnaires’ disease is commonly diagnosed clinically using a urinary antigen test. The urinary antigen test is highly accurate for L. pneumophila serogroup 1, however other diagnostic tests should also be utilized in conjunction with the urinary antigen as many other Legionella species and serogroups are pathogenic. Culturing of patient specimens remains the gold standard for diagnosis of Legionnaires’ disease. Selective media, BYCE with the addition of antibiotics, allows for a high sensitivity and specificity. Culturing can identify all species and serogroups of Legionella. A major benefit of culturing is that it provides the recovery of a patient isolate, which can be used to find an environmental match. Other diagnostic tests, including DFA and molecular tests such as PCR and LAMP, are useful tests to supplement culturing. Molecular tests provide much more rapid results in comparison to culture, however these tests should not be a primary diagnostic tool given their lower sensitivity and specificity in comparison to culturing. It is recommended that all laboratories develop the ability to culture patient specimens in-house with the selective media.

Hyperlactatemia in sepsis

The relationships between lactate kinetics and the physiologic derangements in sepsis are more complex than we once thought.

Babesiosis review

Here is a free full text review on the topic.

Points of interest:

The main species causing human disease are Babesia microti, Babesia divergens and Babesia venatorum.

It is transmitted to humans from rodents via the tick Ixodes scapularis which is the same vector that transmits anaplasmosis and Lyme disease. Coinfection with the latter two should be tested for.

Rare transmission occurs via transfusion.

Asplenia is a risk factor (and is associated with more severe disease) but is not necessary for development of disease.

It is increasingly being recognized in immunocompetent hosts.

Complications include hemolysis, cytopenias (any or all three), hemophagocytic lymphohistiocytosis, DIC, multi organ failure, splenomegaly, splenic infarct and splenic rupture. Many infections are mild and self limiting.

The intracellular forms may be confused with malaria parasites. The maltese cross, though pathognomonic, is often not seen. PCR is available but is not sensitive below 50 parasites per ml.

Raising magnesium awareness

George Lundberg at Medscape.

Management of long QT

It’s complicated:

Recent findings

LQT syndrome remains the most common inherited arrhythmia and is a leading cause for sudden unexplained death accounting for up to 20–25% of cases. Rapid progress of genetic technology over the past 2 decades has significantly improved our understanding of molecular and genetic mechanisms of LQT. Despite all those novel insights, phenotype assessment and appropriate risk stratification in LQT remains challenging – even for the expert.

Summary

This review outlines our current understanding and approach to the clinical diagnosis and management of LQT as well as recent insights into genotype–phenotype correlations. Genetic testing has evolved beyond a pure diagnostic tool and is in addition increasingly integrated as complementary prognostic marker. With regard to the management of LQT, there is now evidence that the protective effect of beta-blockers is rather substance-specific than a class effect. Novel approaches – in conjunction with standard beta-blockers – are emerging including gene-specific treatment for certain subtypes of LQT. A specialized inherited arrhythmia clinic is the preferred resource for the complex risk stratification and individualized management of individuals with LQT.

Unexplained anemia in older men related to low T

From JAMA Internal Medicine:

Question Will testosterone treatment of older men with low testosterone levels and mild anemia improve their anemia?

Findings Testosterone treatment of older men with low testosterone levels and unexplained anemia corrected the anemia more than placebo. This treatment also corrected anemia more than placebo in men who had anemia of known causes, such as iron deficiency.

Meaning Testosterone deficiency in older men results in decreased hemoglobin levels and sometimes in mild anemia. Correcting the testosterone deficiency is associated with increased hemoglobin levels and tends to correct the anemia, even in the presence of a coexisting cause of anemia.

Interesting.

Low FFR predicted events even in lesions that looked “insignificant”

Report here.

Local anesthetic toxicity

Free full text review.

Pulmonary hypertension in left heart disease

From a paper in the American Journal of Medicine:

Highlights

•Echocardiographically tricuspid incompetence gradient of ≥40 mm Hg (pulmonary hypertension surrogate) was found in 18% of first echocardiograms.

•Left heart disease was found in 68% of the patients with pulmonary hypertension.

•Valve disease is the most common pathology in this group.

•Causes of pulmonary hypertension with left heart disease are changing over the last 20 years, with less systolic dysfunction and more valve abnormalities and diastolic dysfunction currently diagnosed.

•Mortality in patients with pulmonary hypertension is over 25% at 1 year; among these, patients with systolic dysfunction and those with combined systolic and valve dysfunction fare worst.

Abstract

Introduction

Pulmonary hypertension has many causes. While it is conventionally thought that the most prevalent is left heart disease, little information about its proportion, causes, and implications on outcome is available.

Methods

Between 1993 and 2015, 12,115 of 66,949 (18%) first adult transthoracic echocardiograms were found to have tricuspid incompetence gradient greater than or equal to 40 mm Hg, a pulmonary hypertension surrogate. Left heart disease was identified in 8306 (69%) and included valve malfunction in 4115 (49%), left ventricular systolic dysfunction in 2557 (31%), and diastolic dysfunction in 1776 (21%). Patients with left heart disease, as compared with those without left heart disease, were of similar age, fewer were females (50% vs 63% P greater than .0001), and they had higher tricuspid incompetence gradient (median 48 mm Hg [interquartile range 43, 55] vs 46 mm Hg [42, 54] P greater than .0001). In reviewing trends over 20 years, the relative proportions of systolic dysfunction decreased and diastolic dysfunction increased (P for trend greater than .001), while valve malfunction remained the most prevalent cause of pulmonary hypertension with left heart disease. Independent predictors of mortality were age (hazard ratio [HR] 1.05; 95% CI, 1.04-1.05; P greater than .0001), tricuspid incompetence gradient (HR 1.02; 95% CI, 1.01-1.02, P greater than .0001 per mm Hg increase), and female sex (HR 0.87; 95% CI, 0.83-0.91, P greater than .0001).

Results

Overall, left heart disease was not an independent risk factor for mortality (HR 1.04; 95% CI, 0.99-1.09; P = .110), but patients with left ventricular systolic dysfunction and with combined systolic dysfunction and valve malfunction had increased mortality compared with patients with pulmonary hypertension but without left heart disease (HR 1.30; 95% CI, 1.20-1.42 and HR 1.44; 95% CI, 1.33-1.55, respectively; P greater than .0001 for both).

Conclusions

Pulmonary hypertension was found to be associated with left heart disease in 69% of patients. Among these patients, valve malfunction and diastolic dysfunction emerged as prominent causes. Left ventricular dysfunction carries additional risk to patients with pulmonary hypertension.

Lactate elevations in critical illness: type a, type b or both?

Here is a recent free full text review.

It points out the following:

Lactate is a semiquantitative indicator of illness severity and risk of mortality. Its elevation indicates need for immediate resuscitative efforts. Decline in the lactate level during resuscitative efforts is a good sign. Lactate elevation can reflect global tissue ischemia. However, in a variety of critical illnesses, even septic shock, lactate is not a reliable indicator of tissue perfusion. This is due to multiple mechanisms, including non ischemic mechanisms, of excess lactate generation. Intense beta receptor stimulation due to high catacholamine levels, for example, increases intracellular cyclic AMP. This results in downstream metabolic effects that drive lactate generation including glycogenolysis (which increases glucose delivery into the glycolytic pathway thus generating lactate) and stimulation of the sodium potassium ATPase which also drives glycolysis. These metabolic (non ischemic) components of lactate generation may not as directly responsive to fluid resuscitation. Thus, using lactate normalization as an endpoint for volume administration may lead to over administration of fluid.

Less is more: calories that is

Here is a recent review on the benefits of caloric restriction.

Leprosy (Hansen’s disease): FAQs

Here are some key points from a couple of reviews. [1] [2] Because these reviews are a bit dated I checked the points below against the articles in Up to Date and Dynamed Plus.

What is the classification?

Discrete categorization is difficult. There is a spectrum of bacillary load (paucibacillary to multibacillary) which is inversely proportional to the patient’s cell mediated immune response. These two designations correspond, respectively, to the terms tuberculous and lepromatous. Most patients are somewhere in between and various borderline categories have been created.

What are leprosy reactions?

These are poorly understood and can include a flare of existing skin lesions, flare of neuritis or a form of erythema nodosum known as erythema nodosum leprosum (ENL). These are inflammatory responses.

What is the treatment?

Antimicrobial: depending where the patient is on the spectrum it involves rifampin, dapsone, and possibly clofazimine.

Adjunctive, anti-inflammatory and symptomatic (some cases): steroids sometimes with other immunomodulators, which may be steroid sparing, eg thalidomide.

What about transmission?

This is poorly understood. It is not highly contagious. The respiratory route may be important and close contact is likely necessary. Nine banded Armadillo exposure is a risk factor in the Southern US.

What are some factors in the host response?

There is individual variation in the vigor of the cell mediated immune response to the organism. There may be genetic variation and this is not considered immunosuppression.

Leisure time physical activity reduces cardiovascular events and mortality in older patients

The effect was dose dependent in this study.

Update on CPR and ACLS

This free full text review was written by Dr. Gordon Ewy, THE expert on BLS and ACLS.

Early discharge time of day is associated with longer LOS

From a recent study:

BACKGROUND

Discharging patients before noon is a key approach to improving bed utilization. Few data exist to describe whether patients are discharged earlier or their stay is extended to allow for an early discharge the next day.

OBJECTIVE

To determine if a discharge before noon (DCBN) is associated with length of stay (LOS).

DESIGN/SETTINGS/PATIENTS

Retrospective analysis of data from adult medical and surgical discharges from a single academic center from July 2012 through April 2015. We used a multivariable generalized linear model to evaluate the association between DCBN and LOS.

RESULTS

Of 38,365 hospitalizations, 6484 (16.9%) were discharged before noon, and the median LOS was 3.7 days. After adjustment, DCBN was associated with a longer LOS (adjusted odds ratio [OR]: 1.043, 95% confidence interval [CI]: 1.003‐1.086). The association between longer LOS and DCBN was more pronounced in patients admitted emergently (n = 14,192, 37%) (adjusted OR: 1.14, 95% CI: 1.033‐1.249).

CONCLUSIONS

Although we cannot discern whether discharges were delayed to achieve discharge before noon, earlier discharge was associated with a longer LOS, particularly among emergent admissions.

How much do we spend on defensive medicine?

From a survey of hospitalists:

The United States spends substantially more per capita for healthcare than any other nation. Defensive medicine is 1 source of such spending, but its extent is unclear. Using a national survey of approximately 1500 US hospitalists, we report the estimates the US hospitalists provided of the percent of resources spent on defensive medicine and correlates of their estimates. We also ascertained how many reported being sued. Sixty-eight percent of eligible recipients responded. Overall, respondents estimated that 37.5% of healthcare costs are due to defensive medicine. Just over 25% of our respondents, including 55% of those in practice for 20 years or more, reported being sued for medical malpractice. Veterans Affairs (VA) hospital affiliation, more years practicing as a physician, being male, and being a non-Hispanic white individual were all independently associated with decreased estimates of resources spent for defensive medicine.

Curbing overuse of the CT pulmonary angiogram in evaluating for pulmonary embolism

From a recent review:

BACKGROUND: Imaging use in the diagnostic workup of pulmonary embolism (PE) has increased markedly in the last 2 decades. Low PE prevalence and diagnostic yields suggest a significant problem of overuse.

PURPOSE: The purpose of this systematic review is to summarize the evidence associated with the interventions aimed at reducing the overuse of imaging in the diagnostic workup of PE in the emergency department and hospital wards.

DATA SOURCES: PubMed, MEDLINE, Embase, and EBM Reviews from 1998 to March 28, 2017.

STUDY SELECTION: Experimental and observational studies were included. The types of interventions, their efficacy and safety, the impact on healthcare costs, the facilitators, and barriers to their implementation were assessed.

DATA SYNTHESIS: Seventeen studies were included assessing clinical decision support (CDS), educational interventions, performance and feedback reports (PFRs), and institutional policy. CDS impact was most comprehensively documented. It was associated with a reduction in imaging use, ranging from 8.3% to 25.4%, and an increase in diagnostic yield, ranging from 3.4% to 4.4%. The combined implementation of a CDS and PFR resulted in a modest but significant increase in the adherence to guidelines. Few studies appraised the safety of interventions. There was a lack of evidence concerning economic aspects, facilitators, and barriers.

CONCLUSIONS: A combined implementation of an electronic CDS and PFRs is more effective than purely educational or policy interventions, although evidence is limited. Future studies of high-methodological quality would strengthen the evidence concerning their efficacy, safety, facilitators, and barriers.

Determining ejection fraction using an I phone

Reported here in Critical Care Medicine.

Knee mottling reflects regional endothelial dysfunction and a worse prognosis in septic shock

From Critical Care.

MACRA skepticism

Here’s Matthew Hahn’s take.

It is based on the dubious idea of “value based purchasing” and promises to be the biggest disruption to our profession since the Prospective Payment System.

What is Jaccoud’s arthropathy and what are the disease associations?

From a recent review:

Jaccoud's arthropathy (JA) is a condition characterised clinically by 'reversible' joint deformities such as swan neck, thumb subluxation, ulnar deviation, 'boutonniere' and hallux valgus, along with an absence of articular erosions on a plain radiograph. JA was initially described in patients with rheumatic fever (RF), but as this disorder has become rare the main clinical entity associated to JA at present is systemic lupus erythematosus (SLE). JA has also been described in other connective tissue diseases, infections and neoplasia. In general, its prevalence in either SLE or RF is around 5%. The etiopathogenic mechanisms of JA are not known, but some authors have suggested an association with hypermobility syndrome. Several studies have attempted to identify an association of different antibodies with JA in SLE patients, but their findings do not allow for the drawing of any definite conclusions. Newer imaging techniques such as magnetic resonance and high-performance ultrasonography have revealed the presence of small erosions in joints of a few patients with JA. Presently, the therapy for JA is conservative and based on the use of non-hormonal anti-inflammatory drugs, low doses of corticosteroids, methotrexate and antimalarials. The role of surgery through either the realignment of soft tissue around the joint--or more aggressive procedures such as arthrodesis, silastic implant and arthroplasty--needs to be proven.

IVIG as treatment for monoclonal gammopathy associated systemic capillary leak syndrome

From a recent study:

Background

Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome.

Methods

We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months.

Results

Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality.

Conclusions

We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.

IVC thrombosis

Free full text review.

Risk factors for DKA in patients taking SGLT2 inhibitors

The use of SGLT2 inhibitors has been associated with DKA in patients with type 2 diabetes. This review examined risk factors for its development. From the paper:

Patients

Thirty-four case reports of patients with type 1 and type 2 diabetes mellitus who developed DKA while receiving an SGLT2i.

Methods and Main Results

This systematic review investigated the relationship between SGLT2i and DKA in patients with diabetes. The existing literature was reviewed with a primary outcome to identify patient-specific factors contributing to the incidence of ketoacidosis in patients with diabetes who were treated with a SGLT2i. Numerous databases were searched to identify appropriate primary literature. Search terms included canagliflozin, dapagliflozin, empagliflozin, SGLT2, sodium glucose cotransporter-2 inhibitor, diabetic ketoacidosis, ketoacidosis, metabolic acidosis, and acidosis. Primary literature was analyzed via descriptive statistics. Thirty-four individual case reports were identified via the primary literature search. Two-thirds (25 cases) involved patients with a diagnosis of type 2 diabetes mellitus (T2DM). The average blood glucose on presentation for SGLT2i-induced DKA was 265.6 ± 140.7 mg/dl (14.7 ± 7.8 mmol/L), with common symptoms including nausea, vomiting, and abdominal pain. Common precipitating factors included patients who were diagnosed with T2DM and were subsequently found to have latent autoimmune diabetes of adulthood, patients who had recently undergone major surgery, or patients who had decreased or discontinued insulin. No cases were fatal.

Conclusion

In this review, episodes of DKA with SGLT2i use were characterized by lower blood glucose levels and were often caused by a precipitating factor. Understanding precipitating factors for SGLT2i-related DKA may help providers better identify patients at risk for development of DKA.

Is there a difference between IgM multiple myeloma and Waldenstrom’s macroglobulinemia? Is it important?

Yes and yes.

Here’s a case report that discusses these questions.