Cardiovascular Function in Long-Term Hematopoietic Cell Transplantation Survivors.

Peak oxygen consumption (VO2peak), as measured by cardiopulmonary exercise testing (CPET), is a powerful independent predictor of cardiovascular disease (CVD) and all-cause mortality in a broad range of populations. We assessed the safety and feasibility of CPET in aging long-term hematopoietic cell transplantation (HCT) survivors, a population at high risk for premature onset of CVD. Next, we examined how organ-specific impairments (eg, cardiac, pulmonary, hematologic) impact VO2peak after HCT. Twenty consecutive HCT survivors underwent a comprehensive assessment of cardiopulmonary health that included CPET, echocardiography with strain, pulmonary function testing, 6-minute walk test, and timed up and go. Median age at assessment was 67.4 years (range, 42 to 75), and median time from HCT was 9.8 years (range, 3 to 20). No adverse events were observed during CPET procedures, and 95% of studies were considered to be at "peak" effort (respiratory exchange ratio ≥ 1.10). VO2peak was on average 22% less than predicted, and allogeneic HCT survivors had markedly lower VO2peak when compared with autologous HCT survivors (18.2 mL/kg/min versus 22.2 mL/kg/min; P = .05). Six participants (30%) had VO2peak ≤ 16 mL/kg/min, a threshold associated with a 9-foldrisk of death in patients undergoing HCT. Despite the presence of normal (>50%) resting left ventricular ejection fraction in all participants, 25% had markedly abnormal left ventricular longitudinal strain, an advanced echocardiographic measure of myocardial dysfunction. These findings highlight the role of stress-based measures and advanced myocardial imaging to characterize CVD risk in HCT survivors, setting the stage for tailored interventions to prevent CVD with its attendant morbidity and mortality.

Long-term pulmonary function in survivors of childhood cancer.

PURPOSE: This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. PATIENTS AND METHODS: Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. RESULTS: Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. CONCLUSION: Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring.

Oxygen for end-of-life lung cancer care: managing dyspnea and hypoxemia.

Oxygen is commonly prescribed for lung cancer patients with advancing disease. Indications include hypoxemia and dyspnea. Reversal of hypoxemia in some cases will alleviate dyspnea. Oxygen is sometimes prescribed for non-hypoxemic patients to relieve dyspnea. While some patients may derive symptomatic benefit, recent studies demonstrate that compressed room air is just as effective. This raises the question as to whether to continue their oxygen. The most efficacious treatment for dyspnea is pharmacotherapy-particularly opioids. Adjunctive therapies include pursed lips breathing and a fan blowing toward the patient. Some patients may come to require high-flow oxygen. High-flow delivery devices include masks, high-flow nasal oxygen and reservoir cannulas. Each device has advantages and drawbacks. Eventually, it may be impossible or impractical to maintain a SpO2 > 90%. The overall goal in these patients is comfort rather than a target SpO2. It may eventually be advisable to remove continuous oximetry and transition focus to pharmacological management to achieve patient comfort.

Speckle tracking echocardiography derived systolic longitudinal strain is better than rest single photon emission tomography perfusion imaging for nonviable myocardium identification.

BACKGROUND: The aim was to compare the speckle tracking echocardiography (STE) derived systolic longitudinal strain (SL(Smax)) with rest single photon emission computed tomography (SPECT) perfusion imaging (Q(REST)), and to define the optimal cut-offs for SL(Smax) to discriminate transmural scar on contrast-enhanced magnetic resonance imaging (ceCMR). METHODS AND RESULTS: In 100 patients with chronic ischemic left ventricular (LV) dysfunction, myocardial viability was assessed using STE and rest SPECT to predict LV segmental relative extent of delayed enhancement (DE) >75% on ceCMR. Correlation was found between regional SL(Smax) (r=-0.59, P<0.0001) and DE on ceCMR. The SL(Smax) optimal cut-off -5.3% identified segments with DE>75% on ceCMR (sensitivity 83.1%, specificity 84.6%). Optimal cut-offs SL(Smax) for segments corresponding to individual perfusion territories (-3.6%, -5.3% and -4.7% for LAD, LCx resp. RCA perfusion territories) were identified. There was a significant difference (AUC 0.866 vs. 0.822 for SL(Smax) resp. Q(REST), p=0.036) in the accuracy of predicting non-viable segment due to the greater accuracy of SL(Smax) than Q(REST) in the RCA perfusion territory (AUC 0.893 vs. 0.75 for SLSmax resp. Q(REST), P=0.001). CONCLUSIONS: STE enabled identification of LV non-viable segments. Cut-off values derived for perfusion territories of individual coronary arteries improve the accuracy of predicting a transmural scar presence. In comparison with rest myocardial SPECT perfusion imaging, STE is more accurate in predicting non-viable myocardium.

Prediction of long-term reverse left ventricular remodeling after revascularization or medical treatment in patients with ischemic cardiomyopathy: a comparative study between SPECT and MRI.

Patients with ischemic heart disease and depressed left ventricular (LV) ejection fraction (LVEF) develop varying degrees of LV remodeling after cardiac surgical revascularization. Fifty-three patients with stable ischemic heart disease and impaired LV function (LVEF 34.9 ± 4%) were prospectively followed up for 24 months. Thirty-seven patients underwent coronary artery bypass grafting (CABG), 16 patients were treated conservatively. Cardiac magnetic resonance imaging (MRI) and SPECT were performed at baseline and after 12 and 24 months of follow-up. The patients were divided into responders and non-responders depending on the degree of LVEF improvement at 24 months follow-up (>5%-responders). MRI with ≤5 segments with DE/wall thickness ratio (DEWTR) ≥50% predicted LV reverse remodeling with a sensitivity of 86% and a specificity of 75% (AUC 0.81). An MRI finding of ≤2 segments with the DEWTR ≥75% had a corresponding sensitivity of 71% and specificity of 67% (AUC 0.75) while fixed perfusion defect on SPECT <16.5% of LV predicted reverse remodeling with a sensitivity of 64% and a specificity of 69% (AUC 0.64). A preoperative number of segments with the DE/wall thickness ratio of ≥50 and ≥75% obtained by MRI, was found to be a better predictor of left ventricular reverse remodeling than fixed perfusion defect by SPECT. No other MRI or SPECT parameter predicted LVEF improvement at 24 months after CABG.

Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial).

BACKGROUND: Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS. METHODS: The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were randomized at admission to fluvastatin 80 mg (N = 78) or placebo (N = 78). Study medication was administered immediately after randomization and then once daily for 30 days; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75% in the fluvastatin group and 78% in the placebo group were on statin therapy. RESULTS: We did not demonstrate any difference between groups in the level of C-reactive protein, interleukin 6, and pregnancy-associated plasma protein A on Day 2 and Day 30 (primary endpoint). Fluvastatin-therapy, however, significantly reduced one-year occurrence of major adverse cardiovascular events (11.5% vs. 24.4%, odds ratio (OR) 0.40, 95% CI 0.17-0.95, P = 0.038). This difference was caused mainly by reduction of recurrent symptomatic ischemia (7.7% vs. 20.5%, OR 0.32, 95% CI 0.12-0.88, P = 0.037). CONCLUSIONS: This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability. Fluvastatin therapy was, however, safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS. TRIAL REGISTRATION: NCT00171275.

How accurately can we predict forced expiratory volume in one second after major pulmonary resection?

Standard formulas for predicting postoperative forced expiratory volume in 1 second (po-FEV1) do not consider bronchi obstructed by tumor or chronic obstructive pulmonary disease, e.g., Formula 1 [ppo-FEV1 = (pre-opFEV,) x (# segments remaining)/(# of total segments)] whereas Formula 2 [ppo-FEV1 = (pre-opFEV,) x (# segments remaining)/(# of total unobstructed segments)] does. A retrospective chart review was conducted to determine accuracy of predicting po-FEV1, at a comprehensive cancer center. Predicted po-FEV, was calculated using different formulas and analyzed using regression analysis and Pearson correlation. We found good correlation between po-FEV1 and predicted po-FEV1 using Formulas 1 and 2. In patients with tumor airway obstruction or chronic obstructive pulmonary disease, predictive accuracy decreased for both formulas. Prediction of FEV1 in patients undergoing pulmonary resection was generally accurate, but major errors were observed in some cases; therefore, better predictive formulas are needed in patients with airway obstruction by tumor or chronic obstructive pulmonary disease.

Intensity of signal contacting meniscal surface in recurrent tears on MR arthrography compared with that of contrast material.

OBJECTIVE: Several previous studies reported that the signal contacting the meniscal surface in a recurrent tear on MR arthrography had intensity equal to that of intraarticular contrast material. Because we failed to diagnose recurrent tears using this criterion, we reviewed our knee MR arthrograms in patients who had prior meniscal surgery. CONCLUSION: On knee MR arthrograms, the signal contacting the surface of a recurrent meniscal tear may be equal to or less than that of adjacent intraarticular gadolinium contrast material.

Fetal enterolithiasis: prenatal sonographic and MRI diagnosis in two cases of urorectal septum malformation (URSM) sequence.

OBJECTIVES: Enterolithiasis (multiple calcifications of intraluminal meconium) is a rare, prenatal ultrasonographic finding. In this study, our aim was to evaluate the prenatal diagnostic features and discuss the management of the patients. METHODS: The data of two cases of prenatally diagnosed fetal enterolithiasis were collected from ultrasound scan, magnetic resonance imaging (MRI) and neonatal or postnatal autopsy records. The findings were evaluated in both prenatal and postnatal periods. Chromosomal analysis was performed in one case. An evaluation of primary and secondary malformations was done. Coexisting anomalies were searched for via radiology, neonatal surgery and histopathology. RESULTS: Malformations in two cases (both males) with partial and complete urorectal septum malformation (URSM) sequence were described. The absence of an anal opening and presence of a fistula between the urinary and gastrointestinal tract were common findings. These features were considered as primary malformations contributing to the formation of enterolithiasis. Secondary anomalies (urinary and gastrointestinal system malformations, pulmonary hypoplasia, genital and other coexisting anomalies) were evaluated. CONCLUSIONS: The prenatal detection of enterolithiasis carries a poor prognosis. Most of the previously reported cases were invariably associated with major fetal malformations of the urinary and gastrointestinal tract. It is a warning sign for large bowel obstruction with or without enterourinary fistula. Therefore, adequate gastrointestinal and urologic studies must be undertaken after birth for the final diagnosis. There is a high mortality rate in the reported cases, mostly attributed to associated anomalies, and all survivors required neonatal surgery. It is important to differentiate the partial from the full URSM sequence because the prognosis in the partial URSM sequence is generally good, with long-term survival being common.

Probability of mortality of critically ill cancer patients at 72 h of intensive care unit (ICU) management.

GOALS: To develop and validate a model for probability of hospital mortality for cancer patients at 72 h of intensive care unit (ICU) management. PATIENTS AND METHODS: This is an inception cohort study performed at four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 827 patients and then validated on an additional 415 patients. Multiple logistic regression modeling was used to develop the models, which were subsequently evaluated for discrimination and calibration. The main outcome measure is in-hospital death. RESULTS: A probability of mortality model, which incorporates ten discrete categorical variables, was developed and validated. All variables were collected at 72 h of ICU care. Variables included evidence of disease progression, performance status before hospitalization, heart rate >100 beats/min, Glasgow coma score 40 mg/dl, and a urine output of <150 ml for any 8 h in the previous 24 h. The p values for the fit of the preliminary and validation models were 0.535 and 0.354 respectively, and the areas under the receiver operating characteristic (ROC) curves were 0.809 and 0.820. CONCLUSIONS: We report a multivariable logistic regression model to estimate the probability of hospital mortality in critically ill cancer patients at 72 h of ICU care. The model is comprised of ten unambiguous and readily available variables. When used in conjunction with clinical judgment, this model should improve discussions about goals of care of these patients. Additional validation in a community hospital setting is warranted.

The effect of early treatment by cerivastatin on the serum level of C-reactive protein, interleukin-6, and interleukin-8 in the patients with unstable angina and non-Q-wave myocardial infarction.

The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris (UAP) or non-Q-wave myocardial infarction (NQMI) can influence the serum level of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) 24 h later. Forty-four patients with rest chest pain and subendocardial ischemia on ECG were randomized to receive cerivastatin 0.3 mg at the time of admission (group C+) to standard therapy or to remain just on standard therapy (group C-). Blood samples for determination of troponin I (TI), CRP, IL-6 and IL-8 were collected at admission (entry level) and 24 h later (final level). Patients with non-physiological baseline levels of TI, as well as patients with progression to Q wave MI were excluded. All baseline, clinical and demographic data and final values of TI were comparable in the two groups. In patients treated with cerivastatin (group C+, n = 13) we observed decrease in the CRP level (-6.73 +/- 3.93 mg/L); on the other hand, in group C- (n = 17) the CRP level increased (+7.92 +/- 2.77 mg/L, p = 0.004). Similar differences were observed also in IL-6: in group C+ the level was significantly reduced as compared with the increase in group C- (-0.76 +/- 0.52 vs. 4.58 +/- 1.49 ng/L, p = 0.005). The level of IL-8 was not affected. Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI; this might positively influence their prognosis. Nevertheless, further studies are needed to support this hypothesis.