Primecuts – This Week in the Journals

September 17, 2018

Waves slam the Oceana Pier & Pier House Restaurant in Atlantic Beach, N.C., Thursday, Sept. 13, 2018 as Hurricane Florence approaches the area. (Travis Long /The News & Observer via AP)

By Michael Natter, MD

Peer Reviewed 

The Hurricane Ravaging the Carolinas.

Much of medicine happens in the microscopic realm. Bacteria, viruses, fungi, the aberrant cells of malignancy, are all invisible to the unaided eye.  In the following sections, we’ll discuss several of these microscopic entities, but before we do let’s acknowledge the macroscopic scale of two massive storms, each hundreds of miles across that are battering thousands of people across the world.  North and South Carolina are currently in the grips of a hurricane Florence.  Already the death toll has risen to 14 and there has been more than 30 inches of rainfall, a new state record.  In the eastern hemisphere, China and the Philippines are experiencing winds of up to 200mph and massive rainfall from Typhoon Mangkut as it sweeps across the sea.

Citation: The New York Times


 Microvascular Outcomes in Patients With Diabetes After Bariatric Surgery Versus Usual Care

A Matched Cohort Study 

Researchers have known for years that type 2 diabetic (T2DM) patients who undergo weight loss surgeries are able to improve their glycemic control (even putting the disease into ‘remission’ in some cases). However, little is known about the implications for microvascular complications of the disease following weight loss surgery. This question was investigated by a retrospective matched cohort designed study across four integrated US healthcare systems where about half of patients received weight loss surgery while the other half had non-surgical interventions. About four thousand T2DM patients (age range 19 to 79) within the Kaiser Permanente healthcare system were matched across numerous clinical criteria including BMI, hemoglobin A1c amongst others. Gastric bypass, sleeve gastrectomy, and gastric banding procedures all counted as surgical interventions. The primary outcome of interest was the development of microvascular disease, here defined as the initial occurrence of DM related nephropathy, retinopathy, or neuropathy.

Patient data was looked at for evidence of microvascular disease from 0 – 7 years following surgery and microvascular disease defined as retinopathy, nephropathy, neuropathy or a combination of any or all of these end points.  The weight loss surgery cohort had about half the risk of developing diabetic associated microvascular complications overall (16.9% vs 34.7%). More specifically, the surgical cohort had a lower incidence at 5 years of diabetic neuropathy (7.2% vs. 21.4%), nephropathy (4.9% vs 10.0%) and retinopathy (7.2% vs. 11.2%).

Diabetes management is particularly difficult for both patient and clinician. There are many variables at play, including numerous medications to juggle. Many patients find the management difficult to balance and in some cases fear the injectable options. The goal is, of course, to control blood glucose to stave off the well-known complications and preventable death. Given this objective data and not withstanding the overt risk of surgery, bringing up the option of weight loss surgery can be another effective tool in the clinician’s arsenal.

Bottom Line: Weight loss surgery (gastric bypass, gastrectomy, gastric sleeve) not only improves glycemic control in T2DM but also decrease the risk of microvascular disease 5 years down the road.

Citation: O’Brien, R., et al. Microvascular Outcomes in Patients With Diabetes After Bariatric Surgery Versus Usual Care. Annals of internal medicine. 2018 Sept 4; 169 (5).


Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance

A Randomized Clinical Trial

Concern for antibiotic resistance in an era of antibiotic overuse is a serious and pervasive issue. This is particularly concerning for patients who present with known antibiotic resistant organisms causing catastrophic infections. Extended-spectrum beta-lactamases are a known mediator in the resistance of many third generation cephalopsorins to Escherichia coli and Klebsiella pneumoniae. These organisms are typically treated with carbapenems, which may in turn select for carbapenem resistance. Researchers looked into the utilization of piperacillin-tazobactam against ceftriaxone-resistant E. Coli and Klebsiella infections, instead of meropenem, a carbapenem, as a means of avoiding potential carbapenem resistance.

A non-inferiority study was performed using parallel groups randomized in a clinical trial that spanned nine countries and 26 hospital centers from 2014 – 2017. Inclusion criteria required at least one positive blood culture for E. coli or Klebsiella that was resistant to ceftriaxone but susceptible to piperacillin-tazobactam. A total of 391 patients were randomly assigned to receive either meropenem or piperacillin-tazobactam. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints included time to clinical improvement (based on days until afebrile and resolution of leukocytosis), days to blood culture negativity, and newly positive blood cultures after initial clearance.  The duration of treatment was dictated by the individual physician in direct care of the patient and­ ranged from 4 to 14 days of treatment. Of those who received piperacillin-tazobactam, there was a 12.3% rate of mortality as compared to the meropenem group, which had a mortality rate of 3.7%. In terms of the secondary outcomes, for the piperacillin-tazobactam group, both clinical and blood culture resolution by the fourth day of treatment was seen in 68.4% compared to 74.6% of the meropenem group. In terms of relapse, there was no significant difference noted between groups.

Bottom line: Despite concern for potential propagation of carbapenem resistance, those E.Coli and Klebsiella infections which are resistant to ceftriaxone, piperacillin-tazobactam is an inferior treatment as compared to meropenem.

Citation: Harris, P., et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance. JAMA. 2018 Sept 11; 320 (10).


Oral Fluoroquinolone and the Risk of Aortic Dissection 

It is widely known that tendon rupture is a potential side effect of fluoroquinolone use, however, possibly by a similar mechanism, there is more to be concerned about. Three previous independent studies have suggested an association between fluoroquinolone use and the increased risk of aortic aneurysm and dissection.  This association is thought to be driven by disturbance in collagen synthesis or structure. This study utilized a case-crossover analysis and case time control to better evaluate this claim. A sample size of 1213 patients with an exposure to fluoroquinolone use within 60 days prior to diagnosis of AA or aortic dissection were studied.  Researchers found that exposure to fluoroquinolones has a significant increased risk of AA or AD and additionally, prolonged exposure to the antibiotic (>14days) was also a significant variable, increasing the risk of AA or AD (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure).  Some limitations of this study include the fact that prescribed antiobiotics does not connote antibiotics taken. Additionally, Those with infection warranting fluoroquinolones would potentially have a clinical presentation warranting more diagnostic imaging, which in turn may have identified chronic incidental AA’s that were not related to the fluoroquinolone use.

Bottom Line: While the overall risk of AA and AD are rare, there is an increased risk of AA and AD associated with fluoroquinolone use, with a length of use >14 days furthering that risk.

Citation: Lee, C-C, et al. Oral Fluoroquinolone and the Risk of Aortic Dissection. JACC, 2018 Sept; 72 (12).  


Outcomes Among Patients With Atrial Fibrillation and Appropriate Anticoagulation Control 

According to the CDC, approximately 9% of Americans over age 65 have atrial fibrillation. Anticoagulation, with either a vitamin K antagonist (VKA), or direct oral anticoagulant (DOACs) is the standard of care for patients with an elevated risk of stroke.  Despite certain advantages of DOACs, many patients remain on VKAs. VKAs benefits are intimately tied to the time within therapeutic range, which can be difficult to maintain given the fluctuations of levels and need for constant monitoring.

A new study looked at if those patients on VKAs with >70% of time within therapeutic range (TTR) will continue to be so over time, and to assess adverse outcomes over time of those patients still within therapeutic range for greater than 70% of the time.

In this study using data from a large Danish registry, only 35.4% of patients had a TTR >70% during the first six months of VKA use.  For those that initially achieved TTR>70%, only 56.6% continued to have TTR>70% during the following year.

Did patients fare any differently depending on their time in the therapeutic range? After controlling for changes in TTR following initiation, patients with TTR >70% had a decreased risk of stroke and bleeding when compared to those with TTR<70%.

Bottom Line: It is difficult to maintain long term time in therapeutic range of VKAs as only about 56.6% of patients manage to do so.

Citation: Bonde, A.N., et al. Outcomes Among Patients With Atrial Fibrillation and Appropriate Anticoagulation Control. JACC. 2018 Sept; 72 (12). Center for Disease Control Website


Dr. Michael Natter is a resident physician at NYU Langone Health

Peer reviewed by Kevin Hauck MD,  Associate Editor, Clinical Correlations 

Image courtesy of Travis Long /The News & Observer via AP