Lipegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in Dutch patients.

BACKGROUND: Chemotherapy (CT)-induced neutropenia and febrile neutropenia (FN) can lead to changes in the treatment plan, potentially worsening the cancer outcome. This study evaluated the effect of the glycopegylated granulocyte-colony stimulating factor lipegfilgrastim, used as primary (PP) or secondary prophylaxis (SP), on treatment modifications in adult patients receiving cytotoxic CT with or without biological/targeted therapy (BT) for solid and haematological tumours. METHODS: This phase 4, prospective, observational study was conducted in eight centres in the Netherlands, in 2015-2017. Other study objectives were to characterise the population of cancer patients receiving lipegfilgrastim, to evaluate the incidence of CT-induced neutropenic events, and to assess safety. RESULTS: Of 142 patients, 73.94% had breast cancer and 55.63% received CT in the adjuvant setting. Most patients received lipegfilgrastim as PP (74.65%) and were at low (34.51%) or high risk (39.44%) of FN. CT dose delays were recorded for 22.64% and 36.11% of patients receiving lipegfilgrastim for PP and SP, respectively. CT dose reductions were recorded for 2.11% of patients; no CT dose omissions and one BT dose omission occurred. FN and grade III/IV neutropenia were reported for 5.63% and 9.86% of patients, respectively; associated hospitalisations were rare. The most frequently lipegfilgrastimrelated adverse events (AE) were myalgia, bone pain, and back pain. Serious AEs (55) were reported for 30 (21.13%) patients. There were two deaths, unrelated to lipegfilgrastim administration. CONCLUSION: Administration of lipegfilgrastim in routine clinical practice in the Netherlands results in limited CT/BT dose modifications and low incidence of neutropenic events, with no new safety concerns.

Hassan Najafi, May 22, 1930-May 20, 2017.

Dr Hassan Najafi, an immigrant from Iran who became the 18th president of The Society of Thoracic Surgeons, died on May 20, 2017. He had also served as chair of the American Board of Thoracic Surgery and the Residency Review Committee for Thoracic Surgery, and was a founding member and first president of the Thoracic Surgery Directors Association. A superb technical surgeon, educator, and investigator, Dr Najafi led the Department of Cardiovascular and Thoracic Surgery at Rush University Medical Center for 25 years. Refined and charismatic, he was wholly devoted to his patients, family, trainees, colleagues, and our profession.

No added value of the age-adjusted D-dimer cut-off to the YEARS algorithm in patients with suspected pulmonary embolism.

Essentials Imaging is warranted in the majority of patients to confirm or rule out pulmonary embolism (PE). The age-adjusted D-dimer (ADJUST) reduced the number of required imaging tests in patients ≥ 50 years. The YEARS algorithm was designed to improve the efficiency in patients with suspected PE. There was no added value of implementing ADJUST in the YEARS algorithm in our cohort. SUMMARY: Background The YEARS algorithm was designed to simplify the diagnostic work-up of pulmonary embolism (PE) and to reduce the number of necessary computed tomography pulmonary angiography (CTPA) scans. An alternative strategy to reduce the number of CTPAs is the age-adjusted D-dimer cut-off (ADJUST) in patients aged 50 years or older. We aimed to investigate whether a combination of both diagnostic strategies might save additional CTPAs. Methods The YEARS algorithm consists of three items (clinical signs of deep venous thrombosis, hemoptysis, 'PE most likely diagnosis') with simultaneous D-dimer testing using a pre-test dependent threshold. We performed a post hoc analysis in 3465 patients managed according to YEARS to compare the number of patients managed without CTPA scans and associated diagnostic failures in hypothetical scenarios with different YEARS-ADJUST combinations. Results Following the YEARS algorithm, 1651 patients (48%) were managed without CTPA; PE was diagnosed in 456 (13%) patients at baseline and 18 patients with initial normal testing suffered venous thromboembolism (VTE) during 3-month follow-up (failure rate 0.61%; 95% confidence interval [CI], 0.36-0.96). If ADJUST had been fully integrated in YEARS, 1627 patients (47%) would have been managed without CTPA (absolute decrease of 0.69%; 95% CI -1.7 to 3.0), at cost of four additional missed PE diagnoses at baseline, for a projected 3-month VTE failure rate of 0.75% (95% CI, 0.49-1.13). None of the other studied scenarios showed relevant improvements in efficiency as well, but all led to more missed diagnoses. Conclusion In our cohort, there was no added value of implementing ADJUST in the YEARS algorithm.

Hepatitis E during lenalidomide treatment for multiple myeloma in complete remission.

Lenalidomide has a central role in the treatment of multiple myeloma and results in improved survival. As with other chemotherapeutics, it can cause several serious side effects. This is the first reported case of hepatitis E during lenalidomide treatment for multiple myeloma in complete remission. In case of liver chemistry abnormalities during lenalidomide treatment, the differential diagnosis should include hepatitis E infection.

The History of the Department of Cardiovascular and Thoracic Surgery at Rush.

The Rush Department of Cardiovascular and Thoracic Surgery received certification by the American Board of Thoracic Surgery (ABTS) to train thoracic surgical residents in 1962. The outstanding clinical faculty, with nationally recognized technical expertise, was eager to provide resident education. The hallmark of the program has been clinical excellence, dedication to patient care, and outstanding results in complex cardiac, vascular, and general thoracic surgical procedures. A strong commitment to resident education has been carried to the present time. Development of the sternotomy incision, thoracic and abdominal aneurysm repair, carotid endarterectomy, along with valve replacement, have been the hallmark of the section of cardiovascular surgery. Innovation in bronchoplastic lung resection, aggressive approach to thoracic malignancy, and segmental resection for lung cancer identify the section of general thoracic surgery. A total of 131 thoracic residents have been trained by the Rush Thoracic Surgery program, and many achieved their vascular certificate, as well. Their training has been vigorous and, at times, difficult. They carry the Rush thoracic surgical commitment of excellence in clinical surgery and patient care throughout the country, both in practice groups and academic centers.

Cardiac shock wave therapy and myocardial perfusion in severe coronary artery disease.

BACKGROUND: Ultrasound guided cardiac shock wave therapy (CSWT) is a noninvasive therapeutic option in the treatment of chronic-refractory angina. Clinical trials have shown that CSWT reduces angina symptoms, improves regional systolic function, LV ejection fraction, myocardial perfusion and quality of life parameters. Absolute measurements of myocardial perfusion before and after CSWT have not been performed so far. METHODS AND RESULTS: We studied a total of 21 CCS III patients with history of CAD and multiple interventions who suffered from disabling angina despite individually optimized medical therapy. An N-13 NH3 PET perfusion scan under adenosine was performed before and after CSWT treatment. CSWT was well tolerated in all patients. Absolute perfusion under adenosine of the global left-ventricular myocardium did not change under therapy or minimal coronary resistance. The treated segments, however, showed in terms of both perfusion and resistance a mild but significant improvement, by 11 and 15 %, respectively, whereas no change could be observed in the remote segments. Considering a threshold of increased perfusion of 5 %, 10 (77 %) out of 13 patients with a better target perfusion improved in their CCS class, whereas 3 (43 %) out of 7 patients without improved target perfusion improved in their CCS class too. CONCLUSION: Standard CSWT has the potential to improve myocardial perfusion of the therapy zone and clinical CAD symptomatology without affecting global myocardial perfusion. As a noninvasive and well tolerated therapeutic option, these data suggest the use of CSWT in patients with end-stage CAD.

Hypertrophic cardiomyopathy in cardiac CT: a validation study on the detection of intramyocardial fibrosis in consecutive patients.

Hypertrophic Cardiomyopathy (HCM) confers a 4-5 %/year-risk for sudden cardiac death. Intramyocardial fibrosis (IF) is associated with this risk. The gold standard of IF visualization is cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE-CMR). In view of a number of CMR-limitations the hypothesis of this study was that late enhanced multi-slice computed tomography (leMDCT) enables demonstration of late enhancement (LE) indicating IF. In a prospective single-center validation study leMDCT research-scans were exclusively performed for IF-imaging in HCM-patients not including non-invasive coronary angiography during first-pass (64-slice; 80 kV; Iopromide, 150 mL, injected 7 min before scanning). Applying a 17-segment-polar-map short cardiac axis views (multiplanar reformations; 5 mm slice thickness) were analysed in order to exclude/detect, localize and measure LE practicing the manual quantification method if present. Finally, leMDCT and LGE-CMR data were unblinded for intermodal correlation. We included n = 24 patients consecutively (64.0 ± 14.5 years of age). LE was demonstrated by LGE-CMR in n = 14/24 patients (prevalence 58 %). Patient- and segment-based sensitivity in leMDCT was 100 and 68 %, respectively. In leMDCT tissue density of LE was 142 ± 51 versus 89.9 ± 19.3 HU in remote myocardium (p < 0.001). Signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR) appeared to be 7.3 ± 3.3 and 2.3 ± 1, respectively. Sizing of LE-area gave 2.2 ± 1.4 cm(2) in leMDCT versus 2.9 ± 2.4 cm(2) in LGE-CMR (r = 0.93). Intra-/interobserver variability was assessed with an accuracy of 0.36 cm(2) (r = 0.91) and 0.47 cm(2) (r = 0.82), respectively. In consecutive HCM patients leMDCT can reliably detect intramyocardial fibrosis marked by LE. In view of a comparatively low SNR and CNR leMDCT may alternatively be applied in case of CMR contraindications.

Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function.

BACKGROUND: There has been debate over how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment. OBJECTIVES: To compare the Hestia criteria with the European Society of Cardiology (ESC) criteria for selecting low-risk patients with PE for outpatient treatment. METHODS: From 2008 to 2010, 496 patients with acute, symptomatic PE were screened and 275 treated at home and 221 treated in the hospital according to the Hestia Study protocol. The Hestia criteria were used to select patients for outpatient treatment. Right and left ventricular (RV and LV) diameters were measured on computed tomography images. RV dysfunction was defined as an RV/LV ratio > 1.0. Patients were classified according to the ESC criteria into low, intermediate and high-risk groups, based on blood pressure and RV dysfunction. During 3 months follow-up adverse events were scored. RESULTS: Adverse events occurred in 22 patients (4.5%) treated in the hospital vs. none of the patients treated at home (P < 0.001). Sensitivity and negative predictive value for adverse outcome were 100% for the Hestia criteria and 96% and 99% for the ESC criteria, respectively. Of the patients treated at home according to the Hestia criteria, 35% were normotensive but had RV dysfunction and were classified as intermediate risk according to the ESC criteria. No adverse events happened in these patients treated at home. CONCLUSIONS: Clinical criteria, such as the Hestia criteria, could be helpful in selecting patients, including those with RV dysfunction who have a low risk of adverse clinical outcome and could be candidates for outpatient treatment.

Left ventricular mass and oxygen uptake in top handball athletes.

The key challenge in athlete's screening is the distinction between abnormal and normal which is hindered by the fact that the adaptation to sports activity in endurance athletes is different to that in power athletes. Especially cardiomyopathies provoke changes in ECG and echocardiography (echo) at an early stage when clinical symptoms are absent. ECG and echo data and their relationship to fitness peculiar to top handball players have never been described. We studied 291 male first league handball players (32 Olympians/47 national players) (25.3±4.4 years). Check up consisted of ECG, spiroergometry and echocardiography. None had T-wave inversions, 3.1% showed early repolarisation abnormalities in the precordial leads. Sokolow-Lyon voltage criterion for left ventricular hypertrophy was positive in 19.3%. Spiroergometry showed a maximum oxygen uptake (peakVO2) of 50.3±7.7 ml/min/kg body weight. LVmass was increased in comparison to normal values. There was a correlation between peakVO2 and LVindex (p<0.001, r=0.341), (LVmass/peak VO2 p=0.053, r=0.125). A relationship between cardiac dimensions and peakVO2 could not be confirmed. In professional handball players early repolarisation abnormalities were less frequent and LVmass was increased when compared with soccer players. The need for normal values for different types of sports is crucial to guarantee a proper evaluation of athletes.

[Echocardiographic tissue Doppler imaging analysis of the systolic and early diastolic velocities of the mitral annulus motion in hypertrophic cardiomyopathy and in top-level athletes]. / Echokardiografische Gewebedoppleranalyse der Mitralringgeschwindigkeiten bei Patienten mit hypertropher Kardiomyopathie und bei Hochleistungssportlern.

BACKGROUND AND OBJECTIVE: Echocardiographic Tissue Doppler Imaging (TDI) has been proposed for the differentiation of pathological left ventricular hypertrophy (e. g. hypertrophic cardiomyopathy, HCM) and physiologic left ventricular hypertrophy (athlete's heart). The aim of this study was the TDI analysis of the systolic (S') and early diastolic (E') velocities in patients (pts.) with non-obstructive hypertrophic cardiomyopathy (HCM) and in top-level athletes in consideration of the previously published cut-off values (S' < 9 cm/s, E' < 9 cm/s). PATIENTS AND METHODS: Pulsed-wave TDI of the systolic and early-diastolic velocities was performed at the lateral and septal mitral annulus in the four-chamber view in 17 HCM pts (12 men; mean age 44 ± 16 years) and 80 consecutive athletes (80 men; mean age 26 ± 5 years). RESULTS: Pts with HCM showed significantly decreased systolic velocities of the septal (S' septal: 5.1 ± 1.2 cm/s versus 9.5 ± 1.5 cm/s, p < 0.001) and lateral mitral annulus (S' lateral: 6.4 ± 2.0 cm/s vs. 10.5 ± 2.1 cm/s, p < 0.001). The early diastolic velocity of the mitral annulus E' was significantly decreased in HCM, too (E' septal: 5.9 ± 2.2 cm/s vs. 13.1 ± 2.9 cm/s, p < 0.001; E' lateral: 8.2 ± 3.0 cm/s vs. 16.5 ± 3.4 cm/s, p < 0.001). CONCLUSION: Tissue Doppler Imaging of the systolic and early diastolic velocity of the mitral annulus might be helpful as a promising additional method for the echocardiographic differentiation between pathological and physiologic left ventricular hypertrophy.

Adenocarcinoma in a 40-year-old colonic interposition treated with Ivor Lewis esophagectomy and esophagogastric anastomosis.

Colon interposition for benign stricture is associated with significant perioperative complications that carry high morbidity and mortality, but long-term sequelae such as further strictures and colonic redundancy are often well-tolerated. These benign complications are frequently described in literature, but adenocarcinoma in the colonic graft is a rare complication. We describe a 60-year-old man with a history of benign esophageal stricture who was treated with colon interposition 40 years ago and presented with dysphagia secondary to stage 1 colon graft adenocarcinoma. He was successfully treated with an Ivor Lewis esophagectomy and primary esophagogastric anastomosis.

Biomarkers of the insulin-like growth factor pathway predict progression and outcome in lung cancer.

BACKGROUND: Insulin-like growth factor 1 (IGF-I), IGF binding proteins (IGFBP) 1 to 7, and C-peptide have been postulated to predict survival in non-small cell lung cancer (NSCLC). Studying serum levels in NSCLC patients treated with surgical resection may provide information on the aggressiveness of tumors and be predictive of disease recurrence. METHODS: Immunobead assays were used to measure pretreatment serum levels of IGF-I, IGFBP1 to IGFBP7, and C-peptide in 100 NSCLC patients. Of these, 59 had no metastatic progression (T1 to T4 N0 M0), whereas 41 had positive lymph nodes (T1 to T4 N1 to N3 M0). Data were analyzed using the Mann-Whitney two-sided rank sum test or Kaplan-Meier curves. RESULTS: Low serum IGFBP5 levels correlated strongly with a positive nodal status (p < 0.001) and any incidence of disease recurrence (p = 0.003). Low serum levels of IGFBP5 also predicted poor recurrence-free survivals in the overall cohort (p ≤ 0.001) and in patients with no nodal metastases (p = 0.027). Conversely, a high serum level of IGFBP7 correlated with positive nodal status (p = 0.008), but was not prognostic for recurrence-free survival. No significant correlations were found for IGFBP5 or IGFBP7 for sex, age, race, smoking history, tumor histology, or fasting state. CONCLUSIONS: IGFBP5 and IGFBP7 had value as biomarkers for identifying NSCLC progression and patient outcome.

Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study.

BACKGROUND: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non-randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. OBJECTIVE: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. PATIENTS AND METHODS: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow-up. RESULTS: Of 297 included patients, who all completed the follow-up, six (2.0%; 95% confidence interval [CI] 0.8-4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3 months of follow-up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08-2.4). CONCLUSION: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).