Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Severity Spectrum.

ImportanceProne positioning improves clinical outcomes in moderate-to-severe acute respiratory distress syndrome and has been widely adopted for the treatment of patients with acute respiratory distress syndrome due to coronavirus disease 2019. Little is known about the effects of prone positioning among patients with less severe acute respiratory distress syndrome, obesity, or those treated with pulmonary vasodilators.ObjectivesWe characterize the change in oxygenation, respiratory system compliance, and dead-space-to-tidal-volume ratio in response to prone positioning in patients with coronavirus disease 2019 acute respiratory distress syndrome with a range of severities. A subset analysis of patients treated with inhaled nitric oxide and subsequent prone positioning explored the influence of pulmonary vasodilation on the physiology of prone positioning.Design setting and participantsRetrospective cohort study of all consecutively admitted adult patients with acute respiratory distress syndrome due to coronavirus disease 2019 treated with mechanical ventilation and prone positioning in the ICUs of an academic hospital between March 11, 2020, and May 1, 2020.Main outcomes and measuresRespiratory system mechanics and gas exchange during the first episode of prone positioning.ResultsAmong 122 patients, median (interquartile range) age was 60 years (51-71 yr), median body mass index was 31.5 kg/m2 (27-35 kg/m2), and 50 patients (41%) were female. The ratio of Pao2 to Fio2 improved with prone positioning in 90% of patients. Prone positioning was associated with a significant increase in the ratio of Pao2 to Fio2 (from median 149 [123-170] to 226 [169-268], p < 0.001) but no change in dead-space-to-tidal-volume ratio or respiratory system compliance. Supine ratio of Pao2 to Fio2, respiratory system compliance, positive end-expiratory pressure, and body mass index did not correlate with absolute change in the ratio of Pao2 to Fio2 with prone positioning. However, patients with ratio of Pao2 to Fio2 less than 150 experienced a greater relative improvement in oxygenation with prone positioning than patients with ratio of Pao2 to Fio2 greater than or equal to 150 (median percent change in ratio of Pao2 to Fio2 62 [29-107] vs 30 [10-70], p = 0.002). Among 12 patients, inhaled nitric oxide prior to prone positioning was associated with a significant increase in the ratio of Pao2 to Fio2 (from median 136 [77-168] to 170 [138-213], p = 0.003) and decrease in dead-space-to-tidal-volume ratio (0.54 [0.49-0.58] to 0.46 [0.44-0.53], p = 0.001). Subsequent prone positioning in this subgroup further improved the ratio of Pao2 to Fio2 (from 145 [122-183] to 205 [150-232], p = 0.017) but did not change dead-space-to-tidal-volume ratio.Conclusions and relevanceProne positioning improves oxygenation across the acute respiratory distress syndrome severity spectrum, irrespective of supine respiratory system compliance, positive end-expiratory pressure, or body mass index. There was a greater relative benefit among patients with more severe disease. Prone positioning confers an additive benefit in oxygenation among patients treated with inhaled nitric oxide

Respiratory Physiology of Prone Positioning With and Without Inhaled Nitric Oxide Across the Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Severity Spectrum.

ImportanceProne positioning improves clinical outcomes in moderate-to-severe acute respiratory distress syndrome and has been widely adopted for the treatment of patients with acute respiratory distress syndrome due to coronavirus disease 2019. Little is known about the effects of prone positioning among patients with less severe acute respiratory distress syndrome, obesity, or those treated with pulmonary vasodilators.ObjectivesWe characterize the change in oxygenation, respiratory system compliance, and dead-space-to-tidal-volume ratio in response to prone positioning in patients with coronavirus disease 2019 acute respiratory distress syndrome with a range of severities. A subset analysis of patients treated with inhaled nitric oxide and subsequent prone positioning explored the influence of pulmonary vasodilation on the physiology of prone positioning.Design setting and participantsRetrospective cohort study of all consecutively admitted adult patients with acute respiratory distress syndrome due to coronavirus disease 2019 treated with mechanical ventilation and prone positioning in the ICUs of an academic hospital between March 11, 2020, and May 1, 2020.Main outcomes and measuresRespiratory system mechanics and gas exchange during the first episode of prone positioning.ResultsAmong 122 patients, median (interquartile range) age was 60 years (51-71 yr), median body mass index was 31.5 kg/m2 (27-35 kg/m2), and 50 patients (41%) were female. The ratio of Pao2 to Fio2 improved with prone positioning in 90% of patients. Prone positioning was associated with a significant increase in the ratio of Pao2 to Fio2 (from median 149 [123-170] to 226 [169-268], p < 0.001) but no change in dead-space-to-tidal-volume ratio or respiratory system compliance. Supine ratio of Pao2 to Fio2, respiratory system compliance, positive end-expiratory pressure, and body mass index did not correlate with absolute change in the ratio of Pao2 to Fio2 with prone positioning. However, patients with ratio of Pao2 to Fio2 less than 150 experienced a greater relative improvement in oxygenation with prone positioning than patients with ratio of Pao2 to Fio2 greater than or equal to 150 (median percent change in ratio of Pao2 to Fio2 62 [29-107] vs 30 [10-70], p = 0.002). Among 12 patients, inhaled nitric oxide prior to prone positioning was associated with a significant increase in the ratio of Pao2 to Fio2 (from median 136 [77-168] to 170 [138-213], p = 0.003) and decrease in dead-space-to-tidal-volume ratio (0.54 [0.49-0.58] to 0.46 [0.44-0.53], p = 0.001). Subsequent prone positioning in this subgroup further improved the ratio of Pao2 to Fio2 (from 145 [122-183] to 205 [150-232], p = 0.017) but did not change dead-space-to-tidal-volume ratio.Conclusions and relevanceProne positioning improves oxygenation across the acute respiratory distress syndrome severity spectrum, irrespective of supine respiratory system compliance, positive end-expiratory pressure, or body mass index. There was a greater relative benefit among patients with more severe disease. Prone positioning confers an additive benefit in oxygenation among patients treated with inhaled nitric oxide

Can pelvic lymph node dissection be omitted in intermediate-risk prostate cancer patients? A SEER-based comparative study using inverse-probability-of-treatment weighting

95 Background: To investigate whether pelvic lymph node dissection (PLND) reduces prostate cancer specific mortality (PCSM) in surgically-treated men with intermediate-risk prostate cancer (Pca). Methods: We identified 44,112 men diagnosed with intermediate-risk Pca from 2004-2009 in Surveillance, Epidemiology and End Results Program (SEER). We used inverse-probability-of-treatment weighting (IPTW) to adjust for baseline characteristics between PLND + radical prostatectomy (RP, N=26,571), versus RP alone (N=17,541) groups; Cox competing-risk model and propensity score-adjusted analyses were used for validation. Gleason scores were based on prostatectomy since biopsy scores were not available for RP-treated patients in SEER from 2004-2009. Results: After a median follow-up of 54 months, there was no survival benefit associated with PLND + RP compared to RP alone (Gray's test, P=0.30). After IPTW adjustment for baseline characteristics, PLND was still not associated with PCSM (AHR: 0.93, 95% CI: 0.65-1.33). This result was consistent with propensity score-adjusted model (AHR=1.05, 95% CI: 0.71-1.55) and the Cox competing-risk model (AHR=1.06, 95% CI: 0.71-1.57). Of men who received RP with PLND, 502 men (1.9%) had pathologically positive lymph nodes, which were associated with a higher risk for PCSM (AHR: 4.02, 95%CI: 1.83-8.84). Conclusions: PLND with RP was not associated with reduced PCSM compared with RP alone in men with intermediate-risk disease, suggesting that PLND is diagnostic but not therapeutic in this patient population. However, a caveat of this study is that risk group was defined by pathologic Gleason score; the 5% of clinically intermediate risk patients who are typically found to have Gleason 8-10 disease at prostatectomy could not be included in this analysis. [Table: see text

Understanding critically ill sepsis patients with normal serum lactate levels: results from U.S. and European ICU cohorts

Abstract While serum lactate level is a predictor of poor clinical outcomes among critically ill patients with sepsis, many have normal serum lactate. A better understanding of this discordance may help differentiate sepsis phenotypes and offer clues to sepsis pathophysiology. Three intensive care unit datasets were utilized. Adult sepsis patients in the highest quartile of illness severity scores were identified. Logistic regression, random forests, and partial least square models were built for each data set. Features differentiating patients with normal/high serum lactate on day 1 were reported. To exclude that differences between the groups were due to potential confounding by pre-resuscitation hyperlactatemia, the analyses were repeated for day 2. Of 4861 patients included, 47% had normal lactate levels. Patients with normal serum lactate levels had lower 28-day mortality rates than those with high lactate levels (17% versus 40%) despite comparable physiologic phenotypes. While performance varied between datasets, logistic regression consistently performed best (area under the receiver operator curve 87–99%). The variables most strongly associated with normal serum lactate were serum bicarbonate, chloride, and pulmonary disease, while serum sodium, AST and liver disease were associated with high serum lactate. Future studies should confirm these findings and establish the underlying pathophysiological mechanisms, thus disentangling association and causation

Who bears the greatest burden of aggressive treatment of indolent prostate cancer?

PurposeThe long-term prostate cancer-specific survival for patients initially managed with active surveillance for low-risk prostate cancer ranges from 97% to 100%. We characterized factors that are associated with aggressive treatment with radical prostatectomy or radiation for indolent prostate cancer (defined as screening-detected, low-risk disease).MethodsThe Surveillance, Epidemiology, and End Results Program was used to extract a cohort of 39,803 men diagnosed with prostate-specific antigen-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and prostate-specific antigen <10) from 2004 to 2010. After socioeconomic profiles were generated from county-linked education and income data, multivariable logistic regression was used to determine whether there were any factors associated with high rates of aggressive treatment.ResultsThe rate of aggressive treatment among all men with indolent prostate cancer was 64.3%. Greater rates of aggressive treatment were experienced by men with high socioeconomic status, Caucasian men, and married men (P < .001 for all cases). The increased adjusted odds for receipt of aggressive therapy were 1.25 (95% confidence interval [CI], 1.17-1.32; P < .001), 1.26 (95% CI, 1.21-1.32; P < .001), and 1.88 (95% CI, 1.80-1.97; P < .001) for men with high socioeconomic status, Caucasian men, and married men, respectively, compared with men with low socioeconomic status, non-Caucasian men, and unmarried men, respectively.ConclusionsAlthough men with high socioeconomic status, Caucasian men, and married men often receive the highest quality health care and have the best outcomes for many cancers, it seems that they are most at risk for the avoidable potential harms of aggressive treatment of indolent prostate cancer. Future policy should encourage more stringent guidelines for deferred treatment and culturally and sociodemographically competent counseling of active surveillance

Who bears the greatest burden of aggressive treatment of indolent prostate cancer?

PurposeThe long-term prostate cancer-specific survival for patients initially managed with active surveillance for low-risk prostate cancer ranges from 97% to 100%. We characterized factors that are associated with aggressive treatment with radical prostatectomy or radiation for indolent prostate cancer (defined as screening-detected, low-risk disease).MethodsThe Surveillance, Epidemiology, and End Results Program was used to extract a cohort of 39,803 men diagnosed with prostate-specific antigen-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and prostate-specific antigen <10) from 2004 to 2010. After socioeconomic profiles were generated from county-linked education and income data, multivariable logistic regression was used to determine whether there were any factors associated with high rates of aggressive treatment.ResultsThe rate of aggressive treatment among all men with indolent prostate cancer was 64.3%. Greater rates of aggressive treatment were experienced by men with high socioeconomic status, Caucasian men, and married men (P < .001 for all cases). The increased adjusted odds for receipt of aggressive therapy were 1.25 (95% confidence interval [CI], 1.17-1.32; P < .001), 1.26 (95% CI, 1.21-1.32; P < .001), and 1.88 (95% CI, 1.80-1.97; P < .001) for men with high socioeconomic status, Caucasian men, and married men, respectively, compared with men with low socioeconomic status, non-Caucasian men, and unmarried men, respectively.ConclusionsAlthough men with high socioeconomic status, Caucasian men, and married men often receive the highest quality health care and have the best outcomes for many cancers, it seems that they are most at risk for the avoidable potential harms of aggressive treatment of indolent prostate cancer. Future policy should encourage more stringent guidelines for deferred treatment and culturally and sociodemographically competent counseling of active surveillance

Incidence and determinants of 1-month mortality after cancer-directed surgery.

282 Background: Death within 1 month of surgery is considered treatment related and serves as an important healthcare quality metric. We sought to identify the incidence of and factors associated with 1-month mortality after cancer-directed surgery. Methods: We used the Surveillance, Epidemiology and End Results Program to study a cohort of 1,110,236 patients diagnosed from 2004-2011 with cancers that are among the 10 most common or most fatal who received cancer-directed surgery. Multivariable logistic regression analyses were used to identify factors associated with 1-month mortality after cancer-directed surgery. Results: 53,498 patients (4.8%) died within 1 month of cancer-directed surgery. Patients who were married, insured, or who had a top 50th percentile income or educational status had lower odds of 1-month mortality from cancer-directed surgery ([adjusted odds ratio (AOR) 0.80; 95% CI 0.79 – 0.82; P<0.001], [AOR 0.88; (0.82 – 0.94); P<0.001], [AOR 0.95; (0.93 – 0.97); P<0.001], and [AOR 0.98; (0.96 – 0.99); P=0.043], respectively). Patients who were non-white minority, male, or older (per year increase), or who had advanced tumor stage 4 disease all had a higher risk of 1-month mortality after cancer-directed surgery, with AORs of 1.13 (1.11 – 1.15), P<0.001; 1.11 (1.08 – 1.13), P<0.001; 1.02 (1.02 – 1.03), P<0.001; and 1.89 (1.82 – 1.95), P<0.001 respectively. Conclusions: Unmarried, uninsured, non-white, male, older, less educated, and poorer patients were all at a significantly higher risk for death within 1 month of cancer-directed surgery. Efforts to reduce 1-month surgical mortality and eliminate sociodemographic disparities in this adverse outcome could significantly improve survival among patients with cancer

Incidence and predictors of prostate cancer death in men with other prior malignancies: An analysis from SEER Database

34 Background: Men with cancer are screened 22% more for prostate cancer (PCa) than men without cancer, yet very little has been published on their prostate cancer outcomes. We aim to describe PCa death and clinical factors associated with dying from PCa in this population. Methods: We studied 22,769 men in the Surveillance, Epidemiology, and End Results database diagnosed with PCa as a second cancer from 1973 to 2006. Proportions of PCa death versus primary-cancer death were calculated, stratified by the nine primary cancers with highest incidence among US men and then further stratified by PCa grade and interval between primary and PCa diagnoses. Results: Urinary-bladder (30.4%), colorectal (27.9%) and lung cancer (10.5%) were the most common primary cancers. Overall, 12.4% of men died from PCa. A greater proportion of patients died from PCa than their first cancer with primary melanoma (11.7 vs 6.97%) and oral cavity/pharynx cancer (15.3 vs 6.98%), a similar proportion for colorectal (14.8% vs 13.7%) and kidney/renal pelvis cancer (11.1 vs 12.7%), but a lower proportion for lung (11.3 vs 42.1%) and bladder cancer (10.8 vs 17.4%). When the interval between cancer diagnoses was more than 5 years, PCa was the leading cause of death for five of the nine cancers. Patients who died from PCa compared to those who died from their primary had higher baseline PSA (39.5 vs 16.9 ng/mL, p<0.001), more Gleason 8-10 (36.7 vs 18.2%, p<0.001), more N1/M1 PCa (2.35 vs 0.30%, p<0.001), were older at PCa diagnosis (74.7 vs 71.9 years, p=0.015), and had a longer interval between diagnoses (63.9 vs 28.8 months, p<0.001). Conclusions: PCa remains a significant cause of mortality when diagnosed as a second cancer, especially if the interval from prior cancer is greater than 5 years, suggesting that treatment of aggressive prostate cancer may be reasonable for many patients with prior cancers