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.

Statins were associated with a decreased risk of peptic ulcer

---in this study.

Sulfonylurea use and myocardial infarct size

The adverse effects of sulfonylureas on macrovascular disease have been known for decades. Now we have this:

Methods

Consecutive STEMI patients admitted in Edmonton, Canada between 2006 and 2011 were enrolled in a regional prospective registry program. Patients with type 2 diabetes were identified from this group and the maximum recorded troponin I (max cTnI) within the first 48 h of chest pain onset was used as the primary outcome to quantify infarct size. The relationship between preadmission sulfonylurea use and max cTnI was assessed using multivariable linear regression to adjust for patient demographics, cardiovascular risk factors, clinical data on admission, ischemia time, reperfusion therapy and preadmission drugs.

Results

There were 560 STEMI patients with type 2 diabetes; mean (standard deviation; SD) age was 63.3 (12.8) years, 395 (70.5%) were male, 216 (38.6%) received primary percutaneous intervention, and 211 (37.7%) received thrombolysis. The max cTnI was higher in 146 sulfonylurea users compared to 414 non-sulfonylurea users (mean (SD): 49.8 (74.3) ng/mL versus 39.9 (50.4) ng/mL, respectively; adjusted between-group difference: 12.9 ng/mL; 95% CI 0.3–25.5; p = 0.044).

Conclusion

This study adds further evidence to the proposed causal relationship between sulfonylureas and adverse cardiovascular events by observing a significant difference in infarct size among type 2 diabetes patients presenting with STEMI. Clinicians should consider this association when prescribing sulfonylureas to manage patients with type 2 diabetes.

Unexplained symptoms

Sometimes it is better for the patient and more intellectually honest to not force a diagnostic label and just acknowledge unexplained symptoms.

ER care in VA hospitals

I found this interesting report from the American Journal of Emergency Medicine:

Conclusions

Veterans Health Administration emergency physicians have primarily clinical responsibilities, and less than half have formal emergency medicine board certification. Despite most VHA EDs having university affiliations, traditional academic activities (eg, teaching and research) are performed in only 1 in 3 VHA EDs. Less than half of VHA EDs have availability of consulting services, including advanced stroke care and women's health.

Checklists, daily goal assessments, and clinician prompts

Here's another “systems improvement” initiative that didn't work. From a recent paper:

Importance The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain.

Objective To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults.

Design, Setting, and Participants This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase.

Interventions Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care.

Main Outcomes and Measures In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients’ severity and the ICU’s baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events.

Results A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line–associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions).

Conclusions and Relevance Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality.

Hypoxic hepatitis

An article on this topic recently appeared in The American Journal of Emergency Medicine. The paper focused on the post cardiac arrest situation but it is seen in other types of circulatory collapse. This entity has also been called ischemic hepatitis and shock liver. From the introduction of the paper:

Hypoxic hepatitis (HH) is frequently observed in critically ill patients and is associated with poor outcomes [1] . In HH, hypoperfusion with subsequent ischemia and passive congestion of the liver, severe systemic arterial hypoxemia, and/or impaired hepatic oxygen extraction induces centrilobular liver cell necrosis 2 3 4 5 . According to Henrion et al [2 6] , a diagnosis of HH could be clinically assumed if the following 3 conditions are met: (1) an appropriate clinical setting of cardiac, respiratory or circulatory failure; (2) a sharp increase in serum aminotransferase levels that reach at least 20 times the upper limit of normal; (3) the exclusion of other causes of acute liver cell necrosis, particularly viral or drug-induced hepatitis.

The complex relationships between obesity, hypertension and CKD

Review here.

Autoimmune hemolytic anemia

Linked here are two great review articles. This one addresses such questions as “What are the differences between warm and cold antibody hemolytic anemias?” “What is the difference between primary and secondary AIHA and what are some of the secondary causes?” “How can the ratio of conjugated to total bilirubin help differentiate between biliary disease and hemolysis as the cause of hyperbilirubinemia?”

This one discusses the pathophysiology of AIHA, explains the roles of antibody and complement, and explains why spherocytes are present in peripheral blood in AIHA.

NEJM report on ACOs

From the paper:

Using Medicare claims from 2009 through 2013 and a difference-in-differences design, we compared changes in spending and in performance on quality measures from before the start of ACO contracts to after the start of the contracts between beneficiaries served by the 220 ACOs entering the MSSP in mid-2012 (2012 ACO cohort) or January 2013 (2013 ACO cohort) and those served by non-ACO providers (control group), with adjustment for geographic area and beneficiary characteristics...

Results

Adjusted Medicare spending and spending trends were similar in the ACO cohorts and the control group during the precontract period. In 2013, the differential change (i.e., the between-group difference in the change from the precontract period) in total adjusted annual spending was −$144 per beneficiary in the 2012 ACO cohort as compared with the control group (P=0.02), consistent with a 1.4% savings, but only −$3 per beneficiary in the 2013 ACO cohort as compared with the control group (P=0.96). Estimated savings were consistently greater in independent primary care groups than in hospital-integrated groups among 2012 and 2013 MSSP entrants (P=0.005 for interaction). MSSP contracts were associated with improved performance on some quality measures and unchanged performance on others.

Conclusions

The first full year of MSSP contracts was associated with early reductions in Medicare spending among 2012 entrants but not among 2013 entrants. Savings were greater in independent primary care groups than in hospital-integrated groups.

So as far as cost savings go these results were modest and somewhat mixed. I have to wonder if the effects of ACOs on costs will mirror what happened in the mid 90s with the wave of managed care, when there was an initial slash in costs but the “success” was short lived, as the reductions were not sustainable. I put very little stock in the statement that there was partial improvement in quality, since quality really means the weak and unproven surrogate of performance.

Another Zika virus review

Free full text from BMJ.

Zika virus review

Free full text via NEJM.

Higher prevalence of pancreatic cancer in patients newly diagnosed with type 2 diabetes

This is an association that has long been suspected. Additional evidence for the association was found in this study.

The effect of high flow nasal oxygen post-extubation, in patients at low risk

From a recently reported study:

Importance Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that conditioned high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy. However, conclusive data about reintubation are lacking.

Objective To determine whether high-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy for preventing reintubation in mechanically ventilated patients at low risk for reintubation.

Design, Setting, and Participants Multicenter randomized clinical trial conducted between September 2012 and October 2014 in 7 intensive care units (ICUs) in Spain. Participants were 527 adult critical patients at low risk for reintubation who fulfilled criteria for planned extubation. Low risk for reintubation was defined as younger than 65 years; Acute Physiology and Chronic Health Evaluation II score less than 12 on day of extubation; body mass index less than 30; adequate secretions management; simple weaning; 0 or 1 comorbidity; and absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, and prolonged mechanical ventilation.

Interventions Patients were randomized to undergo either high-flow or conventional oxygen therapy for 24 hours after extubation.

Main Outcomes and Measures The primary outcome was reintubation within 72 hours, compared with the Cochran-Mantel-Haenszel χ2 test. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis and multiorgan failure, ICU and hospital length of stay and mortality, adverse events, and time to reintubation.

Results Of 527 patients (mean age, 51 years [range, 18-64]; 62% men), 264 received high-flow therapy and 263 conventional oxygen therapy. Reintubation within 72 hours was less common in the high-flow group (13 patients [4.9%] vs 32 [12.2%] in the conventional group; absolute difference, 7.2% [95% CI, 2.5% to 12.2%]; P = .004). Postextubation respiratory failure was less common in the high-flow group (22/264 patients [8.3%] vs 38/263 [14.4%] in the conventional group; absolute difference, 6.1% [95% CI, 0.7% to 11.6%]; P = .03). Time to reintubation was not significantly different between groups (19 hours [interquartile range, 12-28] in the high-flow group vs 15 hours [interquartile range, 9-31] in the conventional group; absolute difference, −4 [95% CI, −54 to 46]; P = .66]. No adverse effects were reported.

Conclusions and Relevance Among extubated patients at low risk for reintubation, the use of high-flow nasal cannula oxygen compared with conventional oxygen therapy reduced the risk of reintubation within 72 hours.

Hepatitis B and C associated glomerular diseases

From a recent review:

The most common histopathologic presentation of HBV-GN is HBV-associated membranous nephropathy, which usually manifests clinically with varying grades of proteinuria and microscopic hematuria. The pathogenesis is likely to be immune complex mediated; however, other host and viral factors have been implicated. The treatment of HBV-GN revolves around antiviral therapy. Various histologic types of glomerular diseases are reported in association with HCV infection, the most frequent being Type 1 membranoproliferative glomerulonephritis, usually in the context of Type 2 mixed cryoglobulinemia. The pathogenesis of HCV-GN can be attributed to glomerular deposition of cryoglobulins or noncryoglobulin-immune complexes. Cryoglobulins typically comprised immunoglobulin Mκ with rheumatoid factor activity. Clinically, patients may present with proteinuria, microscopic hematuria, hypertension, and acute nephritic and/or nephrotic syndrome. The treatment of HCV-GN, especially cryoglobulinemic membranoproliferative glomerulonephritis, encompasses various options including contemporary antiviral therapy with or without conventional and novel immunomodulatory agents.

Mentioned in the body of the paper are several other glomerular diseases that have been associated with hep B as well as polyarteritis nodosa which, though not a cause of glomerulonephritis, can cause renal damage as part of the vasculitis.

How to work up hematuria

This topic was recently reviewed in Advances in Chronic Kidney Disease. From the body of the paper:

On finding a urine dipstick positive for blood, the test should be repeated after several days, to account for any transient causes of MH, such as physical activity, sexual intercourse, or menstruation. If the dipstick remains positive, urine microscopy should be performed to identify RBCs and to define their morphology (dysmorphic or isomorphic)..For our purposes, we define MH as 3 or more RBC/hpf. If no RBCs are visualized, patients should be evaluated for alternative causes of a positive dipstick, such as myoglobinuria. We agree with the CUA guidelines ² and Huussen and colleagues, ³⁵ who suggest that urologic imaging and cystoscopy may not be required if dysmorphic cells or RBC casts are seen, suggesting a glomerular etiology. Such findings should, however, prompt assessment of kidney function and urinary protein excretion. If the patient has a reduced GFR or proteinuria, referral to nephrology is warranted and a kidney biopsy should be considered. For those individuals with isolated glomerular MH, a clinician should assess these patients annually for kidney function changes and/or the development of albuminuria or proteinuria. If isomorphic RBCs are seen on urine microscopy, the clinician should confirm with the patient whether possible benign causes of MH such as recent physical activity or trauma, sexual activity, menstrual bleeding, viral symptoms, or urethral instrumentation may account for these findings. If a benign cause is present, a repeat urinalysis should be done in several weeks to ensure resolution. If the earlier mentioned causes are not identified, imaging of the GU tract is indicated. Although CTU has demonstrated the best testing characteristics, we emphasize the importance of limiting cumulative doses of radiation exposure, especially in younger individuals..alternative imaging modalities should be considered, including US or MR...

If no parenchymal lesion is detected on imaging, the clinician should assess the patient's GU cancer risk factor profile. If risk factors are present, they should be promptly referred to urology for cystoscopy. If a patient has no such risk factors, age should be considered before undergoing cystoscopic evaluation. We consider the evidence presented in the 2012 AUA guidelines inadequate to support cystoscopy for anyone with asymptomatic MH younger than 40 years. Patients with asymptomatic MH aged 50 years or older have sufficient cancer risk to warrant cystoscopy, regardless of risk factor profile. 6 For patients aged 40 to 49 years, the data are unclear; if no risk factors are present, clinical judgment for cystoscopy referral is advised.

Progress in the understanding and treatment of hairy cell leukemia

From a recent review:

Initially a uniformly fatal disease, new therapies in rapid succession transformed HCL into a chronic disease with a normal life expectancy in many cases. More recently, the identification of BRAFV600E mutations in the majority of patients with classic HCL have enabled targeted therapies as a therapeutic option. Additional discoveries into the biology of the disease have identified new subtypes of HCL. Modern approaches to the evaluation and treatment of HCL include detailed molecular analysis which informs therapeutic options, which may consist of traditional therapies such as purine nucleoside analogs, or targeted therapies with antibodies, BTK inhibitors, or BRAF inhibitors, or combination therapy.

Genetics of eosiniphilic esophagitis

This is reviewed in a recent paper. Though not inherited in a simple Mendelian fashion it is a disease of genetic predisposition. This results in considerable overlap with atopic conditions. Some key points:

EoE is a complex genetic disease. Five susceptibility loci have been identified to date.

Three of the EoE predisposition loci are shared across other atopic phenotypes; the remaining two appear to be specific to EoE

The effect sizes of the shared loci are more significant in EoE which may facilitate the characterization of the loci and development of novel therapy.

Fresh fruit consumption and cardiovascular disease

From a recent study:

In Western populations, a higher level of fruit consumption has been associated with a lower risk of cardiovascular disease, but little is known about such associations in China, where the consumption level is low and rates of stroke are high.

Methods

Between 2004 and 2008, we recruited 512,891 adults, 30 to 79 years of age, from 10 diverse localities in China. During 3.2 million person-years of follow-up, 5173 deaths from cardiovascular disease, 2551 incident major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3523 intracerebral hemorrhages were recorded among the 451,665 participants who did not have a history of cardiovascular disease or antihypertensive treatments at baseline. Cox regression yielded adjusted hazard ratios relating fresh fruit consumption to disease rates.

Results

Overall, 18.0% of participants reported consuming fresh fruit daily. As compared with participants who never or rarely consumed fresh fruit (the “nonconsumption” category), those who ate fresh fruit daily had lower systolic blood pressure (by 4.0 mm Hg) and blood glucose levels (by 0.5 mmol per liter [9.0 mg per deciliter]) (P<0 .001="" 0.54="" 0.56="" 0.58="" 0.60="" 0.64="" 0.66="" 0.67="" 0.72="" 0.74="" 0.75="" 0.79="" 10="" a="" across="" adjusted="" amount="" and="" associations="" baseline="" between="" both="" by="" cardiovascular="" characteristics.="" ci="" comparisons="" confidence="" consumed.="" consumption="" coronary="" daily="" death="" defined="" dose="" each="" events="" for="" fresh="" fruit="" hazard="" hemorrhagic="" in="" incidence="" incident="" interval="" ischemic="" log-linear="" major="" nonconsumption="" of="" outcome="" p="" participants="" ratios="" regions="" relationship="" respectively="" response="" similar="" stroke.="" stroke="" strong="" study="" subgroups="" the="" there="" these="" to="" trend="" versus="" was="" were="">

Conclusions

Among Chinese adults, a higher level of fruit consumption was associated with lower blood pressure and blood glucose levels and, largely independent of these and other dietary and nondietary factors, with significantly lower risks of major cardiovascular diseases.

This was a study from China. Note that fresh fruit consumption is a component of the Mediterranean diet.

Hyponatremia in cirrhosis

This was the subject of a recent review in Advances in Chronic Kidney Disease. From the article:

Cirrhosis is characterized by systemic and splanchnic vasodilation that leads to excessive nonosmotic secretion of vasopressin (antidiuretic hormone). Hyponatremia is a common electrolyte abnormality in advanced liver disease that results from the impaired ability of the kidney to excrete solute-free water that leads to “dilutional” hyponatremia—water retention disproportionate to the retention of sodium.

The excessive vasodilation is mediated by nitric oxide (NO). NO synthesis in endothelial cells of cirrhotic patients is induced by high levels of circulating endotoxins translocated from the gut having bypassed the portal circulation.

Besides non osmotic vasopressin release the paper also mentions impaired water delivery to the thick ascending limb of the Loop of Henle as a contributing mechanism.

More from the paper:

Hyponatremia in liver diseases carries the prognostic burden, correlates with the severity of cirrhosis, and, in recent studies, has also been implicated in the pathogenesis of hepatic encephalopathy.

Hyponatremia's contribution to hepatic encephalopathy is complex. Not only do the manifestations of hyponatremic encephalopathy overlap considerably with those of hepatic encephalopathy but hyponatremia is contributory to the pathogenesis of hepatic encephalopathy itself by multiple mechanisms. One of these involves the exhaustion of certain astrocyte functions as a result of the extrusion of ions and organic molecules as an adaptive response to hyponatremia.

As a prognostic indicator, hyponatremia is associated with hepatorenal syndrome and spontaneous bacterial peritonitis.

Although hyponatremia is associated with adverse outcomes in cirrhosis, at what level one should attempt to raise the sodium and by what means are unclear. The article recommends against the use of demeclocycline to treat hyponatremia in cirrhosis despite its popularity in the treatment of hyponatremia of a variety of causes.