Does folic acid protect the kidney?

From JAMA Internal Medicine:

Objective To test whether treatment with enalapril and folic acid is more effective in slowing renal function decline than enalapril alone across a spectrum of renal function…

Design, Setting, and Participants In this substudy of eligible China Stroke Primary Prevention Trial (CSPPT), 15 104 participants with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 or greater, including 1671 patients with CKD, were recruited from 20 communities in Jiangsu province in China.

Interventions Participants were randomized to receive a single tablet daily containing 10 mg enalapril and 0.8 mg folic acid (n = 7545) or 10 mg enalapril alone (n = 7559).

Main Outcomes and Measures The primary outcome was the progression of CKD, defined as a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73 m2 if the baseline eGFR was 60 mL/min/1.73 m2 or more, or a decrease in eGFR of 50% or more if the baseline eGFR was less than 60 mL/min/1.73 m2; or end-stage renal disease….

Results Overall, 15 104 Chinese adults with a mean (range) age of 60 (45-75) years were recruited; median follow-up was 4.4 years. There were 164 and 132 primary events in the enalapril group and the enalapril–folic acid group, respectively. Compared with the enalapril group, the enalapril–folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year; P = .02). Among the participants with CKD at baseline, folic acid therapy resulted in a significant reduction in the risks for the primary event (OR, 0.44; 95% CI, 0.26-0.75), rapid decline in renal function (OR, 0.67; 95% CI, 0.47-0.96) and the composite event (OR, 0.62; 95% CI, 0.43-0.90), and a 44% slower decline in renal function (0.96% vs 1.72% per year, P less than .001). Among those without CKD at baseline, there was no between-group difference in the primary end point.

Conclusions and Relevance Enalapril–folic acid therapy, compared with enalapril alone, can significantly delay the progression of CKD among patients with mild-to-moderate CKD.

Acute kidney injury due to iodinated contrast

From a recent JACC review:

CI-AKI remains a concern for patients undergoing cardiac interventional procedures utilizing intravascular iodinated contrast. This form of renal injury appears to be amenable to volume expansion and to measures to increase urine flow and removal of highly water-soluble contrast. Minimizing contrast by use of ALARA principles and strategies to maximize the benefit of contrast exposure (i.e., revascularization) are reasonable. Although no adjunctive therapy is prophylactic or therapeutic for CI-AKI, statin use appears to reduce the incidence and severity of AKI, whereas continuation of RASi appears to increase the risk for CI-AKI. Further research is needed in the development of less toxic contrast agents, as well as therapies that can reduce cardiorenal complication of interventional cardiovascular procedures. Such agents hold the promise of improving long-term outcomes by minimizing the hazards of intercurrent events, such as ACS, and urgent and planned catheterization procedures.

The review focused on coronary angiography. Conspicuously absent were mention of ascorbic acid and ischemic preconditioning. An earlier review was posted here.

Cellulitis review

This is an excellent review, recently published in JAMA.

It needs to be read in the original but here are a few key points:

When is MRSA coverage needed?

From the article:

There has been increasing concern about antibiotic-resistant bacteria, such as community-acquired methicillin-resistant S aureus (MRSA), which is reflected in the increased use of anti-MRSA antibiotics (eg, vancomycin, trimethoprim-sulfamethoxazole, doxycycline, clindamycin) and broad-spectrum gram-negative antibiotics (eg, β-lactam/β-lactamase inhibitors, levofloxacin, ceftriaxone) during the past decade.40 However, most cases of cellulitis do not involve gram-negative organisms, and in cases of nonpurulent and uncomplicated cellulitis, the addition of antibiotics against community-acquired MRSA did not improve outcomes.41 As such, narrow-spectrum antibiotics against Streptococcus and methicillin-sensitive S aureus remain appropriate. In purulent cellulitis (presence of a pustule, abscess, or purulent drainage), S aureus infection is more likely, as demonstrated by a study of 422 patients who presented with “purulent skin and soft tissue infections” to 11 emergency departments throughout the United States, in which skin surface swab cultures revealed MRSA in 59% of patients, methicillin-sensitive S aureus in 17%, and β-hemolytic streptococci in 2.6%.42 Because methicillin-sensitive S aureus and MRSA can be difficult to differentiate according to clinical features alone,43 MRSA should be considered for purulent infections in known high-risk populations, such as athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, individuals with previous MRSA exposure, and intravenous drug users.44

The authors also recommend MRSA coverage for non purulent cellulitis in certain situations: severe systemic manifestations, rapid spread and immune compromise.

When should the spectrum be extended beyond staph and strep (eg anaerobes, gram negatives)?

Severe systemic manifestations, immune compromise, rapid spread.

What if purulent cellulitis is mild and can be treated with oral antibiotics?

Consider confining the coverage to strep and MSSA (but not MRSA). But if MRSA is deemed important to cover TMP/SMX, doxy or clinda may be acceptable (as well as, of course, linezolid).

What are some unusual organisms to consider in special situations?

Traditional (pharmacologic) immunosupression, HIV: strep pneumo, Mtb, gram negatives, crypto species.

Chronic liver disease, CKD: vibrio species ( including vulnificus), gram negatives (including pseudomonas).

When should nec fash (and other complications) be considered?

From the article:

In cases of suspected necrotizing fasciitis, early surgical assessment is recommended; however, laboratory testing may help differentiate cellulitis from early evolving necrotizing fasciitis. Wall et al75 found in a modeling study that a white blood cell count greater than 15 400 cells/mm3 or serum sodium level less than 135 mEq/L could suggest a diagnosis of necrotizing fasciitis with a sensitivity of 90%, specificity of 76%, positive likelihood ratio of 3.75, and negative likelihood ratio of 0.13. Similarly, Wong et al76 developed the Laboratory Risk Indicator for Necrotizing Fasciitis score according to white blood cell count and levels of C-reactive protein, hemoglobin, serum sodium, creatinine, and serum glucose, which had a sensitivity of 90%, specificity of 95%, positive likelihood ratio of 19.95, and negative likelihood ratio of 0.10. Finally, Murphy et al77 identified that for necrotizing fasciitis among cases in their series, a serum lactate level of 2.0 mmol/L had a sensitivity of 100%, specificity of 76%, positive likelihood ratio of 4.17, and negative likelihood ratio of 0. All of these tests are offered as adjunctive tools, along with history, physical examination, and surgical exploration, to guide diagnosis of necrotizing fasciitis.

Imaging studies are not diagnostic of cellulitis but can help distinguish it from more severe forms of infection and can identify drainable fluid collections, such as abscesses. Osteomyelitis can sometimes complicate cellulitis and when suspected can be best ruled out with magnetic resonance imaging or radiography, if chronic. Furthermore, magnetic resonance imaging or computed tomography can help differentiate cellulitis from necrotizing fasciitis or pyomyositis.78 The appearance of gas on computed tomography scan in the absence of soft tissue trauma or a rim-enhancing fluid collection, as would be found with an abscess, is considered pathognomonic of, but not requisite for, a diagnosis of necrotizing fasciitis.79- 81 A recent study evaluating the utility of modern-day computed tomography scanners demonstrated a positive predictive value of 76% and a negative predictive value of 100% and found that only 36% of cases of necrotizing fasciitis included gas.82

In cases of non response to treatment consider cellulitis mimics and possible derm consultation

Mimics include stasis dermatitis, calciphylaxis, erythema migrans and other conditions.

AL cardiac amyloidosis

This topic was recently reviewed in JACC. Although the focus is on cardiac AL amyloidosis it provides a nice overview of cardiac amyloidosis in general. For those who do not have access to the full text the freely available accompanying audio commentary provides an excellent summary.

GCA and PMR review

This review highlights the emerging role of imaging in the diagnosis of both diseases. In GCA it can be an adjunct, or even an alternative, to biopsy.

Duration of antibiotic therapy in community acquired pneumonia

This new study validates the IDSA guideline recommendation for shorter (around 5 days) antibiotic treatment in CAP.

What's the best treatment strategy for stable CAD in DM 2?

From a recently published study:

Background There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ejection fraction (LVEF).

Objectives This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement.

Methods A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy.

Results Among 5,034 subjects, 15% had LVEF less than 50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT.

Conclusions CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy.

Assessment of volume responsiveness in critically ill patients

From JAMA’s Rational Clinical Examination series:

Objective To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion.

Data Sources and Study Selection Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration.

Data Extraction Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies.

Results A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95% CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95% CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold less than 8 mm Hg) was associated with fluid responsiveness (positive LR, 2.6 [95% CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95% CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index greater than 15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95% CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95% CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95% CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95% CI, 0.07-0.22]; pooled sensitivity, 88%).

Conclusions and Relevance Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.

Is simple pulse pressure measurement a reliable surrogate for CO? There is a relationship but it appears to be non linear as discussed here.

Of interest, CVP measurement had fair test characteristics. Ultrasound measurement of vena cava distensibility was of limited usefulness, and then only in mechanically ventilated patients with no spontaneous respiratory effort.

Antivirals added to steroids for treatment of Bell palsy

From a JAMA Evidence Synopsis:

Clinical Question Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy?

Bottom Line Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias.

AICD use in patients with non-ischemic dilated cardiomyopathy

The original use of the AICD for primary prevention of arrhythmic collapse (other than in patients with channelopathy) was in patients post MI with reduced ejection fraction as validated in the MADIT and MADIT II studies. The indications were expanded to patients with dilated cardiomyopathy of all causes after SCD-HeFT. In SCD-HeFT about half the patients had ischemic DCM and about half non-ischemic. But up to now no one had done this same study on a population composed purely of patients with non-ischemic DCM. That was the subject of this study recently published in NEJM. From the article:

Background

The benefit of an implantable cardioverter–defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).

Methods

In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, less than or equal to 35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.

Results

After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).

Conclusions

In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945.)

But things are not as a superficial reading of the conclusion might indicate. First, if you had a device you were only half as likely to drop dead suddenly (NNT 25). Moreover, although it did not reach statistical significance the point estimate for all cause mortality in the device group was lower.

What are the implications for practice? First, before you exclude a patient with DCM from device therapy you would want to rule out coronary disease. We usually do that anyway but the guidelines give us some wiggle room. Second, for those in whom CAD is ruled out we will have to rethink device recommendations on each individual case. It can be expected, and considered appropriate, that individual clinician judgment and patient preferences will drive decision making and some degree of practice variation.

Skepticism about accountable care organizations

Here is a JAMA Viewpoint piece expressing a negative opinion about ACOs. (A companion article in the same issue was favorable). Key points:

The authors point out that any cost savings attributable to the ACOs appear to be nominal. Moreover they tend to be offset by the bonuses paid out to the participants. These bonuses cannot be considered optional because they are inherent to the core notion of the ACO: that “quality” will be rewarded.

The model creates incentives to integrate services. Thus smaller hospitals close or are merged, resulting in monopolies among health care delivery systems. This reduces competition and tends to drive costs up, not down.

Accountable care organizations: how are they working?

The authors of this JAMA Viewpoint article say the model has been a success, but the arguments are unconvincing. Here are some caveats:

The experiment is in its infancy.

Overall the results are mixed.

Cost savings have been modest and in some cases are diminishing and may prove to be transient. That's what we saw in the managed care experiment of a couple of decades ago.

Statements about quality improvement are suspect because real quality cannot be measured. Outcome data are very soft.

Multiple clinical manifestations of IgG4 related disease (IgG4-RD)

Here are some key issues addressed in a recent review.

What are some of the IgG4 related diseases?

These may coexist in the same patient:

Autoimmune pancreatitis type 1

Mikulicz disease (salivary gland infiltration)

Constrictive pericarditis

Coronary artery aneurysm

Inflammatory abdominal aortic aneurysm (and the related condition retroperitoneal fibrosis)

Sclerosing mediastinitis

Riedel's thyroiditis (and other forms of thyroid involvement)

Sclerosing mastitis

Pulmonary mass or interstitial disease

Hypophysitis

Prostatitis

Lymphadenopathy (Castleman like and other forms)

Tubulointerstitial nephritis

Sclerosing cholangitis (which differs in some features from primary sclerosing cholangitis)

How is IgG4-RD diagnosed?

This has been in a state of some controversy and flux. From the article:

According to an international symposium held in 2011, the diagnosis of IgG4-RD requires both an appropriate histological appearance and increased numbers of IgG4-positive plasma cells (or an elevated IgG4:IgG ratio) in tissue...

In 2011, an “All Japan IgG4 Team,” with the aim to draft comprehensive diagnostic criteria for IgG4-RD 51 ( Table 3 ), proposed three major items 51 69 (1) single or multiple organs involved with diffuse or localized swelling, masses, nodules, and/or hypertrophic lesions; (2) elevated serum IgG4 levels (greater than or equal to 135 mg/dL); and (3) histopathologic features that include marked lymphocytic and plasma cell infiltration and fibrosis, with IgG4-positive plasma cell infiltration (IgG4/IgG-positive cell ratio of greater than or equal to 40% and IgG4-positive plasma cells exceeding 10/HPF). Based on these criteria, patients can be classified into the categories of definite, probable, or possible IgG4-RD.

How do autoimmune pancreatitis (AP) types 1 and 2 differ?

Age: older onset (6^th decade) typical of type 1

Gender: male predominance in type 1, not 2

Relationship to IgG4: present in type 1, not clearly present in 2

Histology: lymphoplasmacytic sclerosing pancreatitis in type 1, idiopathic duct centric pancreatitis in 2

Abdominal pain: common in type 2, not in 1

Other organ involvement common in 1, not 2

Steroid responsiveness characterizes both types but type 1 is more prone to relapse.

IgG-4 related disease overview

Here is an overview from Disease of the Month. IgG-4 diseases include one of the two types of autoimmune pancreatitis and several other conditions:

Immunoglobulin G4-related disease is a rare but increasingly recognized multisystem entity characterized by lymphoplasmacytic tissue infiltration...Related manifestations of this disease include Reidel’s thyroiditis, chronic sclerosing dacryoadenitis, autoimmune pancreatitis (type 1 AIP), retroperitoneal fibrosis, and tubulointerstitial nephritis. Usually occurring in older men, the diagnosis is primarily based upon finding of histopahtologic changes..

High flow nasal cannula vs NIPPV post extubation

From a recent report in JAMA:

Question Is high-flow nasal cannula noninferior to noninvasive ventilation for preventing reintubation and postextubation respiratory failure?

Findings In this multicenter randomized noninferiority clinical trial that included 604 adults, the proportion requiring reintubation was 22.8% with high-flow therapy vs 19.1% with noninvasive ventilation, and postextubation respiratory failure was observed in 26.9% with high-flow therapy vs 39.8% with noninvasive ventilation, reaching the noninferiority threshold.

Meaning High-flow nasal cannula immediately after scheduled extubation was not inferior to noninvasive mechanical ventilation for risk of reintubation and postextubation respiratory failure in patients at high risk of reintubation.

Epilepsy driving laws by state

Here is the database from the epilepsy foundation.

Cystic lung disease as a manifestation of Sjogren Syndrome

From a recent paper in Chest:

Methods Eighty-four patients with primary or secondary SS and chest imaging, chest radiograph, or CT scan were retrospectively evaluated for CLD. Thirteen patients with cysts were found. Baseline characteristics of all patients were collected. A multivariate logistic regression model was used to look for predictors of CLD in patients with CT scan. Additional imaging, SS activity, and complications from CLD and SS were collected for the patients with cysts.

Results CLD had a frequency of 15.4% for all patients with chest imaging. Not all cysts were evident on radiography, and CLD frequency was 30.9% for the patients with chest CT scan. Six patients had cysts without other radiographic findings. CLD was associated with older age (OR, 1.1; 95% CI, 1.0-1.16), a diagnosis of secondary SS (OR, 12.1; 95% CI, 1.12-130.4), and seropositivity for anti-SS-related antigen A/Ro autoantibodies (OR, 26.9; 95% CI, 1.44-93.61). There was no radiologic progression of CLD for 12 patients after a 4-year median follow-up. Lung function did not exhibit temporal worsening. CLD did not correlate with a specific pattern in pulmonary function testing. Two patients had secondary infectious complications of the cysts.

And here is a nice general review of cystic lung disease and its various associations.

Cardiac imaging in pulmonary hypertension

Review here.

Viral infection in community acquired pneumonia

From a recent systematic review and meta-analysis:

Abstract:
The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.



We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.



Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5–27.5%). In studies that obtained lower respiratory samples in greater than 50% of patients, the proportion was 44.2% (95% CI 35.1–53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32–3.31).



Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection.

PE may be hiding out in patients with COPD exacerbation

From a recent systematic review and meta-analysis:

Background COPD patients encounter episodes of increased inflammation, so-called acute exacerbations of COPD (AE-COPD). In 30% of AE-COPD no clear etiology is found. Since there is a well-known crosstalk between inflammation and thrombosis, the objectives of this study were to determine the prevalence, embolus localization and clinical relevance, and clinical markers of pulmonary embolism (PE) in unexplained AE-COPD.
Methods A systematic search was performed using MEDLINE and EMBASE platforms from 1974 – October 2015. Prospective- and cross-sectional studies that included patients with an AE-COPD and used pulmonary CT-angiography for diagnosis of PE were included.
Results The systematic search resulted in 1650 records. Main reports of 22 articles were reviewed and 7 studies were included. The pooled prevalence of PE in unexplained AE-COPD was 16.1% (95% confidence-interval 8.3%-25.8%) in a total of 880 patients. Sixty-eight percent of the emboli found were located in the main pulmonary arteries, lobar arteries or inter-lobar arteries. Mortality and length of hospital admission seem to be increased in patients with unexplained AE-COPD and PE. Pleuritic chest pain and cardiac failure were more frequently reported in patients with unexplained AE-COPD and PE. In contrast, signs of respiratory tract infection was less frequently related to PE.
Conclusions PE is frequently seen in unexplained AE-COPD. Two-thirds of emboli are found at localizations that have a clear indication for anticoagulant treatment. These findings merit clinical attention. PE should receive increased awareness in patients with unexplained AE-COPD, especially when pleuritic chest pain and signs of cardiac failure are present and no clear infectious origin can be identified.

The mechanism of the association, as pointed out in the abstract above, may be the association between inflammation and thrombosis.

Other factors were mentioned as possible mechanisms for the association, as pointed out in a review of the paper by ACP Hospitalist Weekly.

This is not the first time such an association has been mentioned, and I have blogged about it several times in the past including here.

STEMI versus ventricular aneurysm: two ECG prediction tools

Report here.

Pulmonary manifestations of Sjogren's syndrome

This free full text review focuses on the pulmonary manifestations but also covers the disease in general.

Stress ulcer prophylaxis: an example of a non evidence based “standard of care”

Stress ulcer prophylaxis, generally with a PPI, has long been an in house performance measure in many institutions, but the practice was never evidence based. According to this review there is equipoise for a clinical trial.

The emerging link between community acquired pneumonia and cardiac disease

This is a growing concern and was recently reviewed here. From the review:

Recent findings: Recent evidence suggests that a large proportion of deaths from CAP are attributable to cardiovascular disease, including sudden cardiac death, acute myocardial infarction (MI), arrhythmias and cardiac failure. Up to one-third of patients with CAP may experience cardiovascular complications within 30 days of hospital admission, while data also suggest that CAP managed in the community is associated with increased risk of acute MI. The risk is maximal within a few days of hospitalization with CAP and reduces over time. Most studies suggest that risk is still increased at 1 year, and some suggest risk continues to be increased at 10 years post-CAP. This clearly contributes to the well-recognized increased long-term mortality associated with CAP. The mechanism is not entirely clear, but recent published data have better defined the impact of the host response, including systemic inflammation and platelet activation. The contribution of Streptococcus pneumoniae has also been recently investigated, with animal studies suggesting a direct effect of S. pneumoniae on the myocardium, forming microlesions that heal with resulting myocardial fibrosis. Several studies suggest a key role for the pore-forming toxin pneumolysin in S. pneumoniae-induced cardiac toxicity.

Summary: Several therapies have been shown to improve the outcomes in cardiovascular disease, but whether these would be effective in improving outcomes in CAP is unknown. In this review, we argue that cardioprotective treatments may hold the greatest promise in terms of reducing long-term mortality in patients with CAP.

By way of background I have posted extensively about this before [1] [2] [3] [4].

Thrombocytopenia as a prognostic marker in septic shock

This paper was highlighted in ACP Hospitalist Weekly as an important study and although it is the first time thrombocytopenia has been looked at in this way in my view it is not fundamentally new or practice changing. From the paper:

Design: Prospective, multicenter, observational cohort study.

Setting: Fourteen ICUs from 10 French university teaching and nonacademic hospitals.

Patients: Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible.

Intervention: None.

Measurements and Main Results: Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p less than or equal to 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs greater than 150,000/mm3; p less than 0.0001).

Conclusions: This is the first study to investigate thrombocytopenia within the first 24 hours of septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock.

The last statement is not practice changing and almost sounds silly given that all patients with sepsis get at least an automated CBC which routinely includes a platelet count.

TIMI and GRACE perform poorly in the evaluation of patients presenting with chest pain to the ER

From a recent prospective cohort study:

Purpose

The Thrombolysis in Myocardial Infarction (TIMI) and the Global Registry in Acute Coronary Events (GRACE) scores were largely evaluated and validated in stratifying risk of cardiovascular events in patients with chest pain and acute coronary syndrome. Our objective was to compare these 2 scores in predicting outcome in emergency department (ED) patients with undifferentiated chest pain.

Materials and methods

This was a prospective cohort study including patients presenting to 4 EDs with chest pain with nondiagnostic or normal ECG. For all included patients (n = 3125), TIMI and GRACE scores were calculated. Follow-up was conducted at 30-day and 1-year post-ED index admission...

Results

We reported 285 (9.1%) major adverse events at 30 days and 436 (13.9%) at 1 year. In patients with low TIMI (less than or equal to 2) and GRACE (less than 109) scores, a significant proportion had major adverse events at 30 days (5% and 7.5%, respectively) and 1 year (7.9% and 12.9%, respectively). Area under ROC curve at 30 days was 0.66 (95% confidence interval [CI], 0.62-0.71) vs 0.57 (95% CI, 0.53-0.62), respectively, for TIMI and GRACE scores. At 1 year, the area under ROC was 0.67 (95% CI, 0.62-0.71) and 0.65 (95% CI, 0.60-0.70), respectively, for TIMI and GRACE scores.

Conclusions

The TIMI and GRACE scores are not valid in short- and long-term risk stratification in our chest pain patients.

TPA administration in patients with stroke mimic

In patients with stroke mimic one would expect a lower incidence of head bleed as compared to patients with actual stroke because their brain tissues are not as friable. Reported experience confirms that this is the case as pointed out in this review. The incidence of head bleed in stroke mimic is in fact much lower. Comforting as that may seem the perspective offered by the article warrants emphasis:

In summary, the rate of sICH in patients with stroke mimic who receive intravenous thrombolytics is low in published data, although this estimate may be lower than that observed in clinical practice.9 Patients with stroke mimics generally were younger, were women, and had lower NIHSS scores. Fully functional outcome was 3-fold more likely for patients with stroke mimic compared with that for AIS patients. However, the risk of causing harm to even 1 patient given intravenous thrombolytics in the setting of a stroke mimic is concerning,

In ordering troponins, consider the pretest probability

From a recent paper:

Background

In clinical practice, we progressively rely on biomarkers, without estimating the pretest probability. There is not enough support for the use of cardiac troponin (cTn) I in the management of noncardiac patients. We studied the rate at which this test was ordered, the prevalence of detection of a positive result in noncardiac patients, and the impact of this incidental finding on clinical management.

Methodology

Patients admitted from December 2011 to 2013 to our community hospital with diagnosis of noncardiac disease who had positive cTn were included. Data collected included final diagnosis, patient disposition, cardiac monitoring, cardiology consult, and cardiac biomarker testing.

Results

Cardiac troponin I was ordered for 1700 patients in our emergency department. Seven hundred fifty patients had a positive cTn. Of the 750 patients, 412 had a positive cTn without any clinical suspicion of an acute coronary syndrome. An incidental finding of a positive cTn leads to ordering of cTn on average 4 times during admission, cardiac monitoring of 379 (91.99%) patients for at least 1 day, and a cardiac consultation for 268 (63.65%) of these patients. None of these patients was candidates for an invasive cardiac intervention.

TTP presenting as complete heart block

Although we typically think of a pentad of manifestations of TTP and, in fact, have a treatment threshold consisting of microangiopathic hemolytic anemia and thrombocytopenia otherwise unexplained, the disease can cause manifestations in multiple organs. Here is a discussion of cardiac manifestations.

Medical and surgical treatment of primary aldosteronisn

From a recent review:

Treatments for primary aldosteronism (PA) aim to correct or prevent the deleterious consequences of hyperaldosteronism: hypertension, hypokalemia, and direct target organ damage. Patients with unilateral PA considered fit for surgery can undergo laparoscopic adrenalectomy, which significantly decreases blood pressure (BP) and medications in most cases and cures hypertension in about 40%. Mineralocorticoid receptor antagonists (MRA) are used to treat patients with bilateral PA and those with unilateral PA if surgery is not possible or not desired. Spironolactone is more potent than eplerenone, but high doses are poorly tolerated in men. MRA can be replaced or complemented with epithelial sodium channel blockers, such as amiloride. Thiazide diuretics and calcium channel blockers are used when the first-line drugs are insufficient to control BP. Dietary sodium restriction should be implemented in all cases because the deleterious consequences of hyperaldosteronism are dependent on salt loading. Several studies comparing the results of surgery and MRA have reported no differences in terms of BP, serum potassium concentration, or cardiovascular and kidney outcomes, although the benefits of treatment tend to be observed sooner with surgery. Patients with PA display relative glomerular hyperfiltration, which is reversed by specific treatment, revealing CKD in 30% of patients. However, further kidney damage is lessened by the treatment of PA.