By Mariya Rozenblit, MD

Peer Reviewed

The medical community suffered the loss of yet another physician by suicide when a young doctor jumped to her death in New York City last week. There is growing recognition that physicians are at increased risk of suicide compared to the general population. In a recent article in the Washington Post, family physician Dr. Pamela Wible describes her research into physician suicide including the staggering statistic that nearly one million Americans lose their doctors to suicide each year [1].

On a lighter note, let’s recap recent developments in the medical journals.  

Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection

An association between influenza and myocardial infarction (MI) has been suggested since the 1930s. The hypothesis is that infection may cause acute inflammation, biomechanical stress, and vasoconstriction as well as a thrombogenic environment through platelet activation and endothelial dysfunction leading to plaque rupture. A study published in the New England Journal of Medicine last week investigated the association between influenza infection and acute MI. The study included Ontario residents registered for public health insurance who were older than 35 years old, underwent testing for respiratory viruses between 2009 and 2014 and were hospitalized for an MI between 2008-2015 [2]. Duplicate samples were excluded, and unfortunately information regarding symptoms was not available in 40% of cases. The risk interval for MI was defined as 7 days after the respiratory viral panel was collected, and the control interval was defined as up to a year before and one year after the risk interval.

The study found that the incidence ratio for MI was 6.3 (CI 3.25-12.22) for days 1-3 and 5.78 (CI 3.17-10.53) for days 4-7 after a positive influenza test. There was no increase in the incidence of MI on days 8 through 25. The statistical analysis controlled for the calendar month (to adjust for increased prevalence of viral infections during peak months of infection). Older patients and patients with influenza B had higher incidence ratios, but these were not statistically significant.

The data suggests a significant association between influenza and acute MI and that the incidence of MI may be six times higher within 1 week of influenza infection. One potential limitation of this study is that the results may only apply to severe respiratory infections, as most patients with milder symptoms do not undergo respiratory virus testing and these findings may not be generalizable to milder infections.

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

It is unclear whether systemic glucocorticoids improve outcomes in septic shock. Previous trials have either shown higher morbidity and mortality or no benefit to using steroids in this patient population. In a recently published in the New England Journal of Medicine, 3800 patients with septic shock were assigned to receive intravenous hydrocortisone 200 mg daily or placebo for 7 days [3]. The randomized, double-blinded study included adults older than 18 years old who were undergoing mechanical ventilation, with documented or strong clinical suspicion of infection, who met at least two systemic inflammatory response syndrome (SIRS) criteria, and who had been treated with vasopressors or inotropic agents for at least four hours. Patients were excluded if they had another indication to receive systemic steroids, had received etomidate (which has adrenal-suppressant properties), or were likely to die within 90 days from a pre-existing condition. The primary outcome of the study was death from any cause at 90 days after randomization.

There was no significant difference in the primary outcome of mortality at 90 days between the two groups. Patients assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration 3 days in the hydrocortisone group vs 4 days in the placebo group; HR 1.32, CI 1.23-1.41; p<0.001). Duration of mechanical ventilation was also shorter in the hydrocortisone group (median 6 days vs 7 days, HR 1.13, CI 1.05-1.22; p<0.001).

Although the study did not show a mortality benefit of hydrocortisone as an adjunctive treatment in septic shock, it is interesting to note that patients who received hydrocortisone had faster resolution of shock and shorter duration of mechanical ventilation. Perhaps if the study had looked into other outcomes such as end organ dysfunction (using surrogate markers such as renal insufficiency, liver dysfunction or delirium) or secondary infections (catheter-associated UTIs, line infections, ventilator associated pneumonia and skin ulcers), which are more likely to occur with prolonged shock, they would have seen additional benefits. More studies need to be done to explore whether steroids may shorten duration of hospitalization for septic shock and to examine if steroid use is associated with decreased morbidity.

Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance

Approximately 3% of patients over the age of 50 are diagnosed with monoclonal gammopathy of undetermined significance (MGUS), defined as the presence of serum monoclonal protein (M protein) of 3.0 g/dL or less, little or no monoclonal protein in the urine, and absence of hypercalcemia, renal insufficiency, anemia, or bone lesions. These patients typically undergo routine monitoring but data regarding rate of progression to multiple myeloma and survival is limited. A recently published cohort study in the New England Journal of Medicine followed 1384 patients with MGUS residing in southeastern Minnesota for a median follow up period of 34.1 years and measured the primary endpoint of progression to multiple myeloma or plasma-cell or lymphoid disorders [4]. MGUS progressed to multiple myeloma or another plasma-cell of lymphoid disorder in 147 patients (11%), a rate 6.5 times (CI 5.5-7.7) higher than the rate in the control population. The cumulative risk of progression to one of these disorders was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at 40 years.

The study also compared risk of disease progression in IgM and non-IgM MGUS. The study found that the risk of progression among patients with IgM MGUS (RR 10.8, CI 7.5-15) was higher than the non-IgM MGUS (RR 5.7, CI 4.7-6.9). The overall survival rate was not significantly different between the two groups (p=0.12). The most important risk factors for progression were an abnormal serum free light-chain ratio and high serum M protein (>1.5g). The results were controlled for the effects of age at diagnosis and length of follow up. It is important for clinicians to recognize that rates of progression for MGUS are different for IgM vs non-IgM type. Future studies are needed to help determine whether screening for MGUS or monitoring improves outcomes.

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

Ovarian cancer remains one of the most difficult to treat gynecological cancers. Hyperthermia is hypothesized to help with penetration of chemotherapy at the peritoneal surface and to aid in impairing DNA repair. A randomized, multicenter, open-label phase 3 trial of cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) recently published in the New England Journal of Medicine investigated whether HIPEC improved outcomes among patients receiving neoadjuvant chemotherapy for stage III ovarian cancer [5]. Two hundred forty-five patients with stable disease after three cycles of neoadjuvant chemotherapy with carboplatin and paclitaxel were randomized to undergo interval cytoreductive surgery with administration of HIPEC or surgery alone. The primary end point was recurrence free survival. In the intention-to-treat analysis, disease recurrence or death occurred in 89% of patients in the surgery only group compared to 81% in patients in the surgery plus HIPEC group (HR 0.66, CI 0.50-0.87; p=0.003). The median recurrence-free survival was 3.5 months longer in the surgery plus HIPEC group compared to the surgery only group, and the median overall survival was 33.9 months in the surgery only group compared to 45.7 months in the surgery plus HIPEC group.

Although the improvement in recurrence-free survival in the surgery plus HIPEC group is a short (3.5 months), it is significant in a cancer with such a high mortality rate. Notably, the authors did not see any significant differences in rates of postoperative complications, adverse events, or quality of life outcomes between the groups suggesting that this is a well-tolerated treatment.  The trial also had an impressive retention rate, with only three patients lost to follow up. This trial included only one treatment of HIPEC, and it would be interesting to further investigate if multiple treatments of HIPEC or subsequent HIPEC treatments at time of recurrence improves disease-free survival. In an accompanying editorial article, Dr. David Spriggs and Dr. Oliver Zivanovic note that while survival outcomes were better in patients who underwent cytoreductive surgery plus HIPEC, neither group had results that came close to the published results for progression-free survival (approximately 2 years) seen in patients who undergo optimal cytoreduction at the initial surgery [6]. They argue that more trials need to be conducted to elucidate whether it is the intraperitoneal route of administration of chemotherapy, the hyperthermia, the intraoperative administration, or some other factor that is driving the apparent benefit seen in this trial.

MiniCuts

A retrospective cohort study published in JAMA of 10,524 patients with atrial fibrillation showed that surgical left atrial appendage occlusion was associated with a lower risk of readmission for thromboembolism at 3 years [7].

A study recently published in Circulation found that in obese patients with hypertension, Roux-en-Y gastric bypass plus medical therapy resulted in more effective blood pressure control compared to medical therapy alone [8].

A retrospective cohort study in JAMA of 141,311 patients with intracranial hemorrhage, prior use of NOACs was associated with a lower risk of in-hospital mortality compared with prior use of warfarin (adjusted OR 0.75) [9].

Dr. Mariya rozenblit is a 3rd year internal medicine resident at NYU Langone Health

Peer reviewed by Jennifer Riggs, MD, chief resident, internal medicine, NYU Langone Health

 

Image courtesy of Wikimedia Commons           

References:

1. Wible, Pamela. “What I’ve learned from my tally of 757 doctor suicides.” The Washington Post. 13 January 2018. https://www.washingtonpost.com/national/health-science/what-ive-learned-from-my-tally-of-757-doctor-suicides/2018/01/12/b0ea9126-eb50-11e7-9f92-10a2203f6c8d_story.html?utm_term=.262f52fc934e.
2. Kwong JC et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med. 2018 Jan 25; 378(4):345-53. http://www.nejm.org/doi/full/10.1056/NEJMoa1702090.
3. Venkatesh B, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018 Jan 19. http://www.nejm.org/doi/full/10.1056/NEJMoa1705835.
4. Kyle RA, et al. Long-Term Follow-Up of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2018 Jan 18; 378(3):241-249. http://www.nejm.org/doi/full/10.1056/NEJMoa1709974.
5. Van Driel WJ, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan 18;378(3):230-240. https://www.ncbi.nlm.nih.gov/pubmed/29342393.
6. Spriggs, DR and Zivanovic O. Ovarian Cancer Treatment – Are We Getting Warmer: N Engl J Med. 2018 Jan 18; 378 (3): 293-294. http://www.nejm.org/doi/full/10.1056/NEJMe1714556.
7. Friedman DJ, et al. Association between left atrial appendage occlusion and readmission for thromboembolism among patients with atrial fibrillation undergoing cardiac surgery. JAMA 2018;319(4):365-374. https://jamanetwork.com/journals/jama/fullarticle/2670253.
8. Schiavon CA, et al. Effects of Bariatric Surgery in Obese Patients with Hypertension: The GATEWAY Randomized Trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension). Circulation. 2017 Nov 13. http://circ.ahajournals.org/content/early/2017/11/10/CIRCULATIONAHA.117.032130.
9. Inohara T, et al. Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality. JAMA. 2018 Jan 25. https://jamanetwork.com/journals/jama/fullarticle/2670103.

 

 

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