retrospective study

High CRP: a marker for depression in metastatic lung cancer

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Takeaway

  • C-reactive protein (CRP), a measure of inflammation, is a strong predictor of clinically significant depression in patients with lung cancer.
  • Patients with moderate or high inflammation are more likely to have depression.

Why this matters

  • Lung cancer has 1 of the highest rates of comorbid depression among all types of cancer, ranging from 16% to 29%.
  • Inflammation is elevated in both lung cancer and depression.

Study design

  • 109 patients undergoing treatment for stage IV lung cancer.
  • Funding: National Cancer Institute.

Key results

  • 71.8% had NSCLC adenocarcinoma, 6.4% squamous cell carcinoma NSCLC, and 16.5% SCLC; the remaining were unspecified.
  • 23.9% overall had clinically significant depression symptoms.
  • After multiregression analysis, only CRP (log-transformed) was significantly associated with depression (aR2, 0.23; P=.001).
  • After linear regression, CRP was a predictor for approximately 20% of depression variability (aR2, 0.2; P=.001), and patients with clinically significant depression scores had higher median CRP levels (3.4 vs 1.3 mg/mL; P=.003) and were more likely to be receiving advanced lines of treatment (P=.24).
  • Among those with depression, 76.9% had a CRP level ≥1 mg/mL, and 50% had a CRP level ≥3 mg/mL.
  • Only 7 of the patients with clinically significant depression were receiving antidepressants.

Limitations

  • Retrospective study.

Preoperative Hypotension Linked to Mortality Risk

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Researchers analyzed data from a quarter-million surgery patients

In the unadjusted analysis, both preoperative hypertension and hypotension were associated with mortality risk. However, after adjusting for risk factors and confounders, the risk associated with hypertension disappeared, reported lead investigator Robert Sanders, MBBS, PhD, FRCA, of the University of Wisconsin, and colleagues.

Sanders and colleagues analyzed data from more than 250,000 patients from the United Kingdom Clinical Practice Research Datalink who underwent noncardiac surgery. They looked for a link between preoperative blood pressure and 30-day perioperative mortality, adjusting for 29 risk factors including age, gender, race, comorbidities, surgical risk score, and end-organ vascular damage.

For patients with a preoperative systolic blood pressure less than 100 mmHg, mortality risk increased by 40% (OR 1.40; 95% CI 1.05-1.86) in the adjusted analysis. For those with a preoperative diastolic BP less than 40 mmHg, mortality risk increased by approximately 250% (OR 2.49; 95% CI 1.43-4.33).

As preoperative blood pressure decreased below the threshold of 100/40 mmHg, the odds of mortality increased.

“While high blood pressure control is important for long-term health, high blood pressure itself does not impose a significant risk of postoperative death,” the study authors said in a press release. “Rather the health consequences of uncontrolled high blood pressure convey other health risks — therefore we still recommend that patients’ blood pressure should be as well controlled as possible prior to surgery.”

“What these data tell us is that patients with low blood pressure before surgery are at higher risk. What we don’t have is causality. There could be some other factor we haven’t measured which is driving this risk. That will be the next step in our research,” Sanders said in an interview with MedPage Today.

“But we still think this is significant new information,” Sanders said. “It will be important to understand how we can mitigate this risk to make sure these patients are less vulnerable.”

“This study is important because it makes us step back and recognize that hypotension, rather than hypertension, is the dominant problem,” P.J. Devereaux, MD, PhD, of McMaster University in Hamilton, Ontario, toldMedPage Today. Devereaux was not involved in the study.

Physicians should be more aware of hypotension as a potential complication for surgical patients and have good procedures in place for measuring and monitoring it, Devereaux said.

Advising patients to take all of their high blood pressure medicine the morning before surgery might need to be reconsidered in some cases, Devereaux said. “If you have an elderly patient who has fasted overnight and then takes three or four hypertension medications that morning, this might lead to a hypotensive episode that gets them into trouble.”

Richard Dutton, MD, an anesthesiologist at the University of Chicago and Chief Quality Officer for the American Society of Anesthesiologists, was more cautious in interpreting the study results.

“This is a retrospective study, so it can show an association but it can’t prove cause and effect,” Dutton said in an interview with MedPage Today. “And you can’t account for all the variables and potential confounders.” Dutton was not involved in the study.

Hypotensive patients may have fared worse in this study because they were sicker to begin with, Dutton said. A patient going into surgery with low blood pressure may be suffering from internal bleeding, dehydration, uncontrolled diabetes, malnourishment, or any number of maladies.

“Still, this study increases my awareness of low blood pressure as a risk factor, and it raises the possibility that correcting low blood pressure might improve surgical outcomes,” Dutton said.

Prograf Aids in Myopathy-Related Lung Disease

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Study ‘provides some reassurance’ on use of tacrolimus.

The addition of tacrolimus (Prograf) to conventional immunosuppressive therapy improved survival among patients with the inflammatory myopathies complicated by interstitial lung disease, a small, retrospective study found.

During a median follow-up of 25.7 months, event-free survival was significantly longer among patients who received tacrolimus, with a weighted hazard ratio of 0.32 (95% CI 0.14-0.75, P=0.008), according to Shinsuke Yasuda, MD, and colleagues from Hokkaido University in Sapporo, Japan.

In addition, disease-free survival was also longer among tacrolimus-treated patients, with a weighted HR of 0.25 (95% CI 0.10-0.66, P=0.005), the researchers reported in the January issue ofRheumatology.

Interstitial lung disease develops in up to half of patients with polymyositis or dermatomyositis (PM/DM), and is a frequent cause of morbidity and mortality.

High-dose steroids are the first-line treatment for this pulmonary complication in PM/DM, but many patients require additional immunosuppression. In one previous study, 50% of patients were refractory to prednisone alone and the mortality rate of these patients was 50%.

The optimal second-line approach has not been determined, however. Conventional choices have been cyclosporin A and cyclophosphamide.

Tacrolimus has effects similar to those of cyclosporin in its suppression of interleukin-2 production by T cells, but the inhibition is approximately 100-fold higher, and it has been shown to be more effective as a post-transplantation treatment.

“Activated pulmonary T cells play an important role in the development of corticosteroid-resistant PM/DM-related interstitial lung disease. Thus, these activated pulmonary T cells in patients with PM/DM-related interstitial lung disease would be ideal treatment targets,” the authors explained.

“Therefore, we hypothesized that tacrolimus is more effective than cyclosporin for the treatment of severe autoimmune conditions, including PM/DM-related interstitial lung disease,” Yasuda and colleagues wrote.

Accordingly, they conducted a retrospective study of 49 patients seen in their center between 2000 and 2013, adjusting the data with inverse probability of treatment weighting statistical methods to limit the influence of bias.

All patients received 0.8 to 1 mg/kg/day of oral prednisone. If additional immune suppression was needed, they were given intravenous methylprednisolone pulse therapy, cyclosporin in dosages of 2 to 3 mg/kg/day, intravenous cyclophosphamide, 500 mg/m2/month, or tacrolimus beginning in oral dosages of 1 to 3 mg/day.

Relapse was defined as worsening of symptoms, radiologic progression of the interstitial lung disease, and the need for increased treatment.

A total of 32 of the patients had dermatomyositis and 17 had polymyositis. Two-thirds were men, and mean age at onset was 52.

Tacrolimus was given as part of the regimen for 25 patients. Among the tacrolimus group, 18 also received steroid pulses, and nine were given cyclophosphamide. None of the tacrolimus patients received cyclosporin.

Among the conventional therapy group, 10 had steroid pulses, seven received cyclosporin, and two were given cyclophosphamide.

Relapses were seen in five patients in both the conventional therapy and tacrolimus groups. One patient receiving tacrolimus died from respiratory disease, as did five in the conventional group. Other serious adverse events were reported in one patient in the tacrolimus group (liver cirrhosis) and in two of the conventional therapy group (malignancies).

Other events included a case of cytomegalovirus and two cases of herpes zoster in the tacrolimus group, and kidney dysfunction in two patients in the conventional therapy group.

In both groups, there were improvements in muscle strength and spirometry tests by 1 year, but no between-group differences were seen.

“To the best of our knowledge, this retrospective study is the first report statistically demonstrating that the addition of tacrolimus significantly improves the event-free and disease-free survival of patients with PM/DM-related interstitial lung disease,” the researchers noted.

Limitations of the study included its retrospective design and the use of varying combinations in treatment. It also was not randomized, but the authors pointed out that because the condition is life-threatening, randomized trials are difficult.

“Therefore, it is meaningful that we have shown the efficacy of tacrolimus as an additional treatment of PM/DM-related interstitial lung disease using systematic statistical methods,” they wrote.

In an accompanying editorial, Patrick Gordon, PhD, and Bibek Gooptu, MD, of King’s College in London, agreed that the the study design had limitations and called for further research.

“Given the paucity of data in this area, [the study] represents an important addition to the current literature. It provides some reassurance for the use of tacrolimus in moderate to severe idiopathic inflammatory myopathy-associated interstitial lung disease and sets the scene for future prospective studies,” Gordon and Gooptu observed.