Pulmonary vascular & cardiovascular network: Cardiovascular medicine & surgery section
Targeted temperature management (TTM) after cardiac arrest: How cool?
Recent randomized control trials, TTM2 (Dankiewicz J. N Engl J Med. 2021;384:2283) and HYPERION (Lascarrou J-B. N Engl J Med. 2019;381:2327), of therapeutic hypothermia, as opposed to normothermia, in patients who remain comatose after return of spontaneous circulation (ROSC) after cardiac arrest have produced conflicting results regarding survival and neurologic benefit. TTM2 reported no benefit to cooling to 33°C, while HYPERION found improved neurologic outcome at 90 days in patients cooled to 33°C. The European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recently released an evidence review and guideline for adults who remain comatose after cardiac arrest (Sandroni C. Intensive Care Med. 2022;48:261). These guidelines recommend continuous monitoring of core temperature in all patients who remain comatose after cardiac arrest, and preventing fever (>37.7°C) for 72 hours, but with no recommendation of target temperature of 32°C vs 36°C.
Differences in patient populations, presenting rhythm during arrest, duration of CPR, and time to target temperature likely each contribute to the disparate conclusions of previous trials. For example, HYPERION enrolled patients with out of hospital cardiac arrest with initial nonshockable rhythms and found benefit to cooling to 33°C. In comparison, TTM2 enrolled all patients with ROSC following arrest (regardless of rhythm), including patients with in-hospital cardiac arrest and found no benefit in therapeutic cooling. Differences in patient populations are underscored by the widely differing percentage of patients with good neurologic outcome in their respective control groups: approximately 30% in the TTM2 trial and 6% in HYPERION. The guidelines leave significant room for clinical judgment in employing therapeutic cooling but encourage the continuous monitoring of core temperature and active avoidance of fever.
Fiore Mastroianna, MD
Section Member-at-Large
Chest infections & disaster response network: Chest infections section
Update on LTBI treatment: Ensuring success by simplifying, shortening, and completing treatment
My patient has a positive IGRA test result – what’s next?
If TB disease is ruled out by clinical, radiographic, and microbiologic assessment (if indicated), then latent TB infection (LTBI) is established, and treatment should be offered, guided by shared-decision making between provider and patient.
Courtesy CHEST
Dr. Sebastian Kurz
What options are available?
While the former standard 9-month regimen of isoniazid-monotherapy can be shortened to 6 months, shorter rifamycin-based regimens are now preferred in most cases and include:
4 months rifampin daily, 3 months isoniazid plus rifampin daily, or 3 months isoniazid plus rifapentine weekly. In addition, 1 month of isoniazid plus rifapentine daily has recently been shown to be effective in people with HIV.
Courtesy CHEST
Dr. Amee Patrawalla
How to choose?
Rifamycin-based regimens have been shown to have less hepatotoxicity and higher completion rates. Drug-drug interactions are of potential concern, for example, in patients receiving anticoagulation or treatment for HIV. The clinician should be aware of rifamycins causing a flu-like illness that may be treatment-limiting. In patients with known contact to drug-resistant TB, regimens are individualized.
How to monitor?
Adherence and completion are the keys to success. Directly observed therapy may be indicated in certain scenarios. Baseline and monthly blood work is recommended for people with risk factors for hepatic or bone marrow toxicity. More importantly, patients should be instructed to discontinue LTBI medications and call the clinician with any new symptoms. HIV testing should be offered to all patients if status is unknown. Clinicians are encouraged to reach out to one of four regional TB Centers of Excellence for guidance.
Sebastian Kurz, MD, FCCP
Amee Patrawalla, MD, MPH, FCCP
Section Members-at-Large
References
Testing and Treatment of Latent Tuberculosis Infection in the United States: Clinical Recommendations. A Guide for Health Care Providers and Public Health Programs. Copyright © 2021 by the National Society of Tuberculosis Clinicians and National Tuberculosis Controllers Association
1. Shah, D. Latent tuberculosis infection. N Engl J Med. 2021;385:2271-80.
2. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):111-115.
3. Swindells et. al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380:1001-11.
Thoracic oncology & chest procedures network: Lung cancer section
Adjuvant and neoadjuvant therapies in early stage lung cancer
Since the discovery of the epidermal growth factor receptor (EGFR) mutation in 2004 and the development of checkpoint blockade in 2006, personalized treatment options for non–small cell lung cancer (NSCLC) have exploded, but targeted systemic therapy medications were only recommended among patients with metastatic or locally advanced disease (Rivera MP, Matthay RA. Clin Chest Med. 2020;41[1]:ix-xi). However, in November 2020, the National Comprehensive Cancer Network (NCCN) updated guidelines to recommend EGFR testing in surgically resected stage IB-IIIA adenocarcinoma, and to consider adjuvant osimerintib in those who were mutation-positive (NCCN. Nov 2020). Interim analysis of an ongoing phase-3 trial showed 89% of patients in the osimertinib group were alive and disease-free at 24 months compared with 52% in the placebo group (hazard ratio 0.20, P < .001) (Wu YL, et al. N Engl J Med. 2020;383[18]:1711-23).
Courtesy CHEST
Dr. Sohini Ghosh
The FDA has also recently approved the use of neoadjuvant and adjuvant immunotherapy in combination with platinum-based chemotherapy. Nivolumab is now approved as neoadjuvant therapy in patients with resectable IB-IIIA NSCLC regardless of PDL-1 status. The Checkmate-816 trial showed increased median event-free survival in the immunotherapy plus chemotherapy group of 31.6 months vs 20.8 months in the chemotherapy-only group (FDA.gov. 2022, Mar 4). Atezolizumab is also now approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells. Median disease-free survival was not reached in patients in the atezolizumab groups vs 35.3 months in the best supportive care group (FDA.gov. 2021, Oct 15). With so many advances in the personalized treatment among all stages of NSCLC, this is a hopeful new chapter in the care of patients with NSCLC.
More information: https://www.nccn.org/guidelines/guidelines-process/transparency-process-and-recommendations/GetFileFromFileManager?fileManagerId=11259
Sohini Ghosh, MD
Section Member-at-Large