Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury.

BACKGROUND: Cardiac surgery-related acute kidney injury (CS-AKI) results in increased morbidity and mortality. Different models have been developed to identify patients at risk of CS-AKI. While models that predict dialysis and CS-AKI defined by the RIFLE criteria are available, their predictive power and clinical applicability have not been compared head to head. METHODS: Of 1388 consecutive adult cardiac surgery patients operated with cardiopulmonary bypass, risk scores of eight prediction models were calculated. Four models were only applicable to a subgroup of patients. The area under the receiver operating curve (AUROC) was calculated for all levels of CS-AKI and for need for dialysis (AKI-D) for each risk model and compared for the models applicable to the largest subgroup (n = 1243). RESULTS: The incidence of AKI-D was 1.9% and for CS-AKI 9.3%. The models of Rahmanian, Palomba and Aronson could not be used for preoperative risk assessment as postoperative data are necessary. The three best AUROCs for AKI-D were of the model of Thakar: 0.93 [95% confidence interval (CI) 0.91-0.94], Fortescue: 0.88 (95% CI 0.87-0.90) and Wijeysundera: 0.87 (95% CI 0.85-0.89). The three best AUROCs for CS-AKI-risk were 0.75 (95% CI 0.73-0.78), 0.74 (95% CI 0.71-0.76) and 0.70 (95% CI 0.73-0.78), for Thakar, Mehta and both Fortescue and Wijeysundera, respectively. The model of Thakar performed significantly better compared with the models of Mehta, Rahmanian, Fortescue and Wijeysundera (all P-values <0.01) at different levels of severity of CS-AKI. CONCLUSIONS: The Thakar model offers the best discriminative value to predict CS-AKI and is applicable in a preoperative setting and for all patients undergoing cardiac surgery.

Absence of association between whole blood viscosity and delirium after cardiac surgery: a case-controlled study.

BACKGROUND: Delirium after cardiothoracic surgery is common and associated with impaired outcomes. Although several mechanisms have been proposed (including changes in cerebral perfusion), the pathophysiology of postoperative delirium remains unclear. Blood viscosity is related to cerebral perfusion and thereby might contribute to the development of delirium after cardiothoracic surgery. The aim of this study was to investigate whether whole blood viscosity differs between cardiothoracic surgery patients with and without delirium. METHODS: In this observational study postoperative whole blood viscosity of patients that developed delirium (cases) were compared with non-delirious cardiothoracic surgery patients (controls). Cases were matched with the controls, yielding a 1:4 case-control study. Serial hematocrit, fibrinogen, and whole blood viscosity were determined pre-operatively and at each postoperative day. Delirium was assessed using the validated Confusion Assessment Method for the Intensive Care Unit or Delirium Screening Observation scale. RESULTS: In total 80 cardiothoracic surgery patients were screened of whom 12 delirious and 48 matched non-delirious patients were included. No significant difference was found between both groups in fibrinogen (p = 0.36), hematocrit (p = 0.23) and the area under curve of the whole blood viscosity between shear rates 0.02 and 50 s(-1) (p = 0.80) or between shear rates 0.02 and 5 s(-1) (p = 0.78). CONCLUSION: In this case control study in cardiothoracic surgery patients changes in whole blood viscosity were not associated with the development of delirium.

Mild preoperative renal dysfunction as a predictor of long-term clinical outcome after coronary bypass surgery.

BACKGROUND: Renal dysfunction is a prognostic marker in patients with cardiovascular disease. However, no long-term follow-up studies on the influence of mild renal dysfunction on mortality in patients undergoing coronary bypass grafting have been reported. Therefore, we aimed to identify the significance of preoperative (mild) renal dysfunction as a long-term predictor of clinical outcome after coronary bypass surgery. METHODS: In 358 patients who underwent isolated saphenous vein aorta-coronary artery bypass grafting, estimated glomerular filtration rates were calculated with the Cockroft-Gault equation (GFRc). Patients were categorized into 2 groups (group 1, GFRc >71.1 mL x min (-1) x 1.73 m (-2) ; group 2, GFRc <71.1 mL x min (-1) x 1.73 m (-2) ). Multivariate Cox proportional hazard analyses were performed to determine the independent prognostic value of GFRc. RESULTS: During a median follow-up of 18.2 years, 233 patients (65.1%) died. Patients who died had lower GFRc and were older. Multivariate analysis demonstrated that total mortality in patients with lower GFRc was significantly increased (lower GFRc group vs normal GFRc group: hazard ratio, 1.44; P = .019). Lower GFRc was also an independent predictor of cardiac mortality (hazard ratio, 1.51; P = .032). No significant differences were observed between groups in the occurrence of myocardial infarction and the need for reintervention. CONCLUSIONS: Our study demonstrates that after long-term follow-up, preoperative mild renal dysfunction is an independent predictor of long-term (cardiac) mortality in patients who undergo coronary artery bypass grafting.

The Carpentier-Edwards Classic and Physio mitral annuloplasty rings: a randomized trial.

OBJECTIVE: To evaluate clinical and echocardiographic outcomes for the semi-flexible Carpentier-Edwards Physio and the rigid Classic mitral annuloplasty ring. METHODS: Ninety-six patients were randomized for either a Classic (n = 53) or a Physio (n = 43) ring from October 1995 through July 1997. Mean follow-up was 5.1 years (range .1-6.6). We included standard patient characteristics at baseline and during follow-up. Analyses were adjusted for age and gender, and for factors that differed across groups at baseline. In 2002, echocardiography was performed in 74% of the survivors. RESULTS: We found a 16% difference in mortality: 14% in the Physio group (n = 6) and 30% in the Classic group (n = 16) (adjusted P = .41). Life table analysis shows that the absolute risk of death after 30 months is lower in the Physio group. Intra-operative repair failure occurred in 3 patients (6%) of the Classic group, and in 4 (9%) of the Physio group, resulting in mitral valve replacement. Late failure occurred in 1 patient (2%) in the Classic group, and in 4 (9%) in the Physio group. At follow-up, left ventricular function did not differ across groups (ejection fraction 45% and 48% (adjusted P = .65)). The combined NYHA class III-IV had improved for the Classic group in 42% and for the Physio group in 34%. CONCLUSION: Although the 16% difference in mortality did not reach statistical significance, it is considered clinically important. No differences in morbidity, valve function, and left ventricular function were found. Further research to explain the difference in mortality is required.

Anticoagulation therapy after bioprosthetic aortic valve replacement in Dutch cardiothoracic centres: acceptance of guidelines does not lead to overall implementation†.

In 2012, the Netherlands Association of Cardiothoracic Surgery accepted the new guidelines of the European Association for Cardio-Thoracic Surgery on antiplatelet and anticoagulation management in cardiac surgery. The aim of our study was to evaluate knowledge and implementation of these guidelines in Dutch cardiothoracic centres 8 months later, specifically after biological aortic valve replacement. One month prior to and 8 months after acceptance of the new guidelines, a questionnaire was sent to all 16 Dutch cardiothoracic centres about their current anticoagulation management after biological aortic valve replacement, their knowledge and implementation of the guidelines. All centres returned the questionnaire. Fifteen centres declared knowledge of the guidelines of which two adjusted their anticoagulation therapy. Four declared they did not follow the guidelines. However, of the remaining 11 centres, only 7 followed the guidelines. Between the centres, current anticoagulation therapy varied from aspirin to coumarin with different dosages and durations. Despite acceptance of the guidelines, only 7 of 16 centres followed them, and there remains great variability in the postoperative anticoagulation management after biological aortic valve replacement in Netherlands.

Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial.

BACKGROUND: During coronary artery bypass graft (CABG) surgery, ischaemia and reperfusion damage myocardial tissue, and increased postoperative plasma troponin concentration is associated with a worse outcome. We investigated whether metformin pretreatment limits cardiac injury, assessed by troponin concentrations, during CABG surgery in patients without diabetes. METHODS: We did a placebo-controlled, double-blind, single-centre study in an academic hospital in Nijmegen (Netherlands) in adult patients without diabetes undergoing an elective on-pump CABG procedure. We randomly assigned patients (1:1) in blocks of ten via a computer-generated randomisation sequence to either metformin hydrochloride (500 mg three times per day) or placebo (three times per day) for 3 days before surgery. The last dose was given roughly 3 h before surgery. Patients, investigators, trial staff, and the statistician were all masked to treatment allocation. The primary endpoint was the plasma concentration of high-sensitive troponin I at 6, 12, and 24 h postreperfusion after surgery, analysed in the per-protocol population with a mixed-model analysis using all these timepoints. Secondary endpoints included the occurrence of clinically relevant arrhythmias within 24 hours after reperfusion, the need for inotropic support, time to detubation, duration of stay in the intensive-care unit, and postoperative use of insulin. This study is registered with ClinicalTrials.gov, number NCT01438723. FINDINGS: Between Nov 8, 2011, and Nov 22, 2013, we randomly assigned 111 patients to treatment (57 to metformin and 54 to placebo). Five patients dropped out from the metformin group, and six from the placebo group. 52 patients in the metformin group and 48 patients in the placebo group were included in the per-protocol analysis. Geometric mean high-sensitivity troponin I increased from 0 µg/L to 3·67 µg/L (95% CI 3·06-4·41) with metformin and to 3·32 µg/L (2·75-4·01) with placebo at 6 h after reperfusion; 2·84 µg/L (2·37-3·41) and 2·45 µg/L (2·02-2·96), respectively, at 12 h; and to 1·77 µg/L (1·47-2·12) and 1·60 µg/L (1·32-1·94) at 24 h. The concentrations did not differ significantly between the groups (difference 12·3% for all timepoints [95% CI -12·4 to 44·1] p=0·35). Occurrence of arrhythmias did not differ between groups (three [5·8%] of 52 patients who received metformin vs three [6·3%] of 48 patients who received placebo; p=1·00). There was no difference between groups in the need for inotropic support, time to detubation, duration of stay in the intensive-care unit, or postoperative use of insulin. No patients died within 30 days after surgery. Occurrence of gastrointestinal discomfort (mostly diarrhoea) was significantly higher with metformin than with placebo (11 [21·2%] of 52 vs two [4·2%] of 48 patients; p=0·01). INTERPRETATION: Short-term metformin pretreatment, although safe, does not seem to be an effective strategy to reduce periprocedural myocardial injury in patients without diabetes undergoing CABG surgery. FUNDING: Netherlands Organisation for Health Research and Development and Netherlands Heart Foundation.

Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer.

BACKGROUND: The role of surgery after neoadjuvant chemotherapy in patients with stage IIIB non-small cell lung cancer (NSCLC) remains unclear. METHODS: A prospective multicenter trial of neoadjuvant chemotherapy followed by surgery or radiotherapy or both was conducted with 41 patients with stage IIIB NSCLC. End points were toxicity, response, downstaging, complete resectability, and survival. The diagnostic value of repeat mediastinoscopy after neoadjuvant chemotherapy (three courses of gemcitabine/cisplatin) was also studied. RESULTS: Response rate after neoadjuvant chemotherapy was 66% (27 of 41). Fifteen patients underwent repeat mediastinoscopy, which proved to be inadequate in 6 patients. Two repeat mediastinoscopies were false negative. Resection was performed in 18 patients, of which 10 proved to be radical. Hospital mortality was 2.4% (n = 1). Major complications occurred in 6 patients (fistula, empyema, hemorrhage). Histopathologically proven downstaging was seen in 16 patients (39%). Twenty-five patients underwent radiotherapy of whom 14 were diagnosed with stable/progressive disease and 9 with partial/complete response. Median survival for all patients was 15.1 months, for nonresponders 8.4 months and for responders 16.8 months (p = 0.11). Patients with partial/complete response had a mean survival of 21.5 months after resection and 13.0 months after radiotherapy (p = 0.0003). CONCLUSIONS: Radical surgery can be performed in 37% (10 of 27) of the responders resulting in a prolonged survival. Surgery as part of combined modality treatment is feasible in stage IIIB NSCLC. Results of a repeat mediastinoscopy are disappointing and proved to be a not-so-effective restaging tool because of the high number of incomplete procedures and because it yields false negative results.

Surgical treatment of Pancoast tumours.

Due to its localisation in the apex of the lung with invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, a superior sulcus tumour causes characteristic symptoms, like arm or shoulder pain or Horner's syndrome. If rib invasion is the only feature, lysis of the rib must be evident on the chest radiograph; otherwise the tumour cannot be defined as a Pancoast tumour. It is important to adequately stage the tumour, because staging significantly influences survival. Survival is better for T3 than T4 tumours and mediastinal lymph node involvement has been found to be a negative prognostic factor. Also Horner's syndrome and incompleteness of resection worsen survival. The management of superior sulcus tumours has evolved over the past 50 years. Before 1950 it was considered to be inoperable and uniformly fatal. Shaw and Paulson introduced combined modality treatment and for many years, this combination of radiotherapy and surgery was the treatment of choice with a mean 5-year survival of approximately 30%. Postoperative radiotherapy or brachytherapy does not improve survival in patients with complete or incomplete resection. The tumour can be resected through the classic posterior Shaw-Paulson approach or the newer anterior transcervical approach, introduced by Dartevelle. This method facilitates better exposure of the extreme apex of the lung, brachial plexus and subclavian vessels. Regarding the extent of pulmonary resection, en bloc resection of the involved ribs with a lobectomy is recommended. Recent multimodality studies, involving chemoradiotherapy and surgical resection, show promising results regarding completeness of resection, local recurrence and survival, provided that appropriate staging has been carried out. However, careful patient selection and adequate perioperative management with protection of the bronchial stump or anastomosis are important to achieve reasonable rates of morbidity and mortality. As brain metastases remain one of the most common forms of relapse, further studies are needed to examine the role of prophylactic cranial irradiation in patients with complete resection. Also the addition of other chemotherapy agents or biologic agents such as angiogenesis inhibitors or tyrosine kinase inhibitors gives a new perspective in the treatment of Pancoast tumours.

Results of surgical treatment of T4 non-small cell lung cancer.

OBJECTIVE: Because of location and invasion of surrounding structures, the role of surgical treatment for T4 tumors remains unclear. Extended resections carry a high mortality and should be restricted for selected patients. This study clarifies the selection process in non-small cell T4 tumors with invasion of the mediastinum, recurrent nerve, heart, great vessels, trachea, esophagus, vertebral body, and carina, or with malignant pleural effusion. METHODS: From 1977 through 1993, 89 patients underwent resection for primary non-small cell T4 carcinomas. Resection was regarded as complete in 34 patients (38.2%) and incomplete in 55 patients (61.8%). Actuarial survival time was calculated and risk factors for late death were identified. RESULTS: Overall hospital mortality was 19.1% (n=17). Mean 5-year survival was 23.6% for all hospital survivors, 46.2% for patients with complete resection and 10.9% for patients with incomplete resection (P=0.0009). In patients with complete resection, mean 5-year survival for patients with invasion of great vessels was 35.7%, whereas mean 5-year survival for invasion of other structures was 58.3% (P=0.05). Age, mediastinal lymph node involvement, type of operative procedure, and postoperative radiotherapy did not significantly influence survival. CONCLUSION: In certain T4 tumors complete resection is possible, resulting in good mean 5-year survival especially for tumors with invasion of the trachea or carina. High hospital mortality makes careful patient selection imperative.

Fibrosis and electrophysiological characteristics of the atrial appendage in patients with atrial fibrillation and structural heart disease.

PURPOSE: This study was conducted to investigate the degree of fibrosis in atrial appendages of patients with and without atrial fibrillation (AF) undergoing cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can be identified by electrogram fractionation and low voltage for potential ablation therapy. METHODS: Interstitial fibrosis from right (RAA) and/or left atrial appendages (LAA) was studied in patients with sinus rhythm (SR, n = 8), paroxysmal (n = 21), and persistent AF (n = 20) undergoing coronary artery bypass and/or aortic or mitral valve surgery. Atrial fibrosis quantification was performed with Masson trichrome staining. Intraoperative bipolar epicardial electrophysiological measurements were performed to correlate fibrosis to electrogram fractionation, voltage, and AF cycle length. RESULTS: The average degree of fibrosis was 11.2 ± 7.2 % in the LAA and 22.8 ± 7.6 % in the RAA (p < 0.001). Fibrosis was not significantly higher in paroxysmal AF patients compared to SR subjects (18.2 ± 8.7 versus 20.7 ± 5.3 %). Persistent AF patients had a higher degree of LAA and RAA fibrosis compared to paroxysmal AF patients (LAA 14.6 ± 8.7 versus 8.6 ± 4.7 %, p = 0.02, and RAA 28.2 ± 7.9 versus 18.2 ± 8.7 %, respectively, p = 0.04). The left atrial end diastolic volume index was higher in persistent AF patients compared to SR controls (38.3 ± 16.4 and 28 ± 11 ml/m(2), respectively, p = 0.04). No correlation between atrial fibrosis and electrogram fractionation or voltage was found. CONCLUSION: Patients with structural heart disease undergoing cardiac surgery have more fibrosis in the RAA than in the LAA. Furthermore, RAA fibrosis is increased in persistent AF but not paroxysmal AF patients compared to control subjects. Electrogram fractionation and low voltage did not provide accurate identification of the fibrotic substrate.

Mediastinal staging in daily practice: endosonography, followed by cervical mediastinoscopy. Do we really need both?

OBJECTIVES: In patients with lung cancer, endosonography has emerged as a minimally invasive method to obtain cytological proof of mediastinal lymph nodes, suspicious for metastases on imaging. In case of a negative result, it is currently recommended that a cervical mediastinoscopy be performed additionally. However, in daily practice, a second procedure is often regarded superfluous. The goal of our study was to assess the additional value of a cervical mediastinoscopy, after a negative result of endosonography, in routine clinical practice. METHODS: In a retrospective cohort study, the records of 147 consecutive patients with an indication for mediastinal lymph node staging and a negative result of endosonography were analysed. As a subsequent procedure, 124 patients underwent a cervical mediastinoscopy and 23 patients were scheduled for an intended curative resection directly. The negative predictive value (NPV) for both diagnostic procedures was determined, as well as the number of patients who needed to undergo a mediastinoscopy to find one false-negative result of endosonography (number needed to treat (NNT)). Clinical data of patients with a false-negative endosonography were analysed. RESULTS: When using cervical mediastinoscopy as the gold standard, the NPV for endosonography was 88.7%, resulting in a NNT of 8.8 patients. For patients with fluoro-2-deoxyglucose positron emission tomography positive mediastinal lymph nodes, the NNT was 6.1. Overall, a futile thoracotomy could be prevented in 50% of patients by an additional mediastinoscopy. A representative lymph node aspirate, containing adequate numbers of lymphocytes, did not exclude metastases. CONCLUSIONS: In patients with a high probability of mediastinal metastases, based on imaging, and negative endosonography, cervical mediastinoscopy should not be omitted, not even when the aspirate seems representative.

Completeness of lung cancer surgery: is mediastinal dissection common practice?

OBJECTIVES: In patients with early-stage non-small cell lung cancer, surgery offers the best chance of cure when a complete resection, including mediastinal lymph node dissection, is performed. A definition for complete resection and guidelines for intra-operative lymph node staging have been published, but it is unclear whether these guidelines are followed in daily practice. The goal of this study was to evaluate the extent of mediastinal lymph node dissection routinely performed during lung cancer surgery, and hereby the completeness of resection according to the guidelines of the European Society of Thoracic Surgery (ESTS) for intra-operative lymph node staging. METHODS: In a retrospective cohort study, the extent of mediastinal lymph node dissection was evaluated in 216 patients who underwent surgery for lung cancer with a curative intent in four different hospitals, three community hospitals and one university hospital. Data regarding clinical staging, the type of resection and extent of lymph node dissection were collected from both the patient's medical record and the surgical and pathology report. Based on histology, location and side of the primary tumour, the extent of mediastinal dissection was compared with the ESTS guidelines for intra-operative lymph node staging. RESULTS: According to the surgical report interlobar and hilar lymph nodes were dissected in one-third of patients. A mediastinal lymph node exploration was performed in 75% of patients; however, subcarinal lymph nodes were dissected in <50% of patients and at least three mediastinal lymph node stations were investigated in 36% of patients. In 35% of the mediastinal stations explored, lymph nodes were sampled instead of a complete dissection of the entire station. A complete lymph node dissection according to the guidelines of the ESTS was performed in 4% of patients. Despite an incomplete dissection unexpected mediastinal lymph nodes were found in 5% of patients. CONCLUSIONS: In daily practice, the intended curative resection for lung cancer cannot be considered complete in the majority of patients, because of an incomplete lymph node dissection according to the current guidelines of the ESTS.

The clinical value of lymphatic micrometastases in patients with non-small cell lung cancer.

INTRODUCTION: In early stage non-small cell lung cancer (NSCLC), presence of lymphatic micrometastases and isolated tumor cells, primarily detected by immunohistochemistry, is suggested to be a prognostic factor. However, there is no consensus whether immunohistochemistry should be used routinely in lymph node assessment.The goal of our study was to determine whether recurrent disease is associated with the presence of lymphatic micrometastases and/or isolated tumor cells, at the time of the lung resection. METHODS: We retrospectively analyzed the prevalence of lymphatic micrometastases and/or isolated tumor cells in two groups of patients, who underwent a curative resection for early stage NSCLC. Group I had a follow-up of 5 years without recurrent disease. Group II consisted of a matched group of patients with recurrent disease. Patients were originally classified as having negative mediastinal lymph nodes.All lymph nodes obtained by mediastinoscopy and thoracotomy were re-examined by serial sectioning and immunohistochemistry. RESULTS: Micrometastases and/or isolated tumor cells were found in one of 16 patients in group I, which was significantly different from six of 16 patients in group II. (Fisher exact test, 4.6; p, 0.04; risk ratio, 2.4).Serial sectioning and immunohistochemistry did not change N-stage for the single patient in group I, in contrast to all six patients in group II. CONCLUSION: Presence of lymphatic micrometastases and/or isolated tumor cells is associated with distant recurrence in patients with early stage NSCLC. We recommend the routine use of serial sectioning and immunohistochemistry in lymph node assessment to improve the accuracy of staging.

[Descending necrotizing mediastinitis: the need for early diagnosis and aggressive treatment]. / Descenderende necrotiserende mediastinitis vroeg herkennen en intensief behandelen.

Three patients developed descending necrotizing mediastinitis (DNM): a 44-year-old man due to poor dental status; a 54-year-old women due to a throat infection, 6 weeks after a tooth extraction; and a 30-year-old man a few days after a tooth extraction. Presenting symptoms were dyspnoea, fever, trismus, cervical oedema, and pain. The first two patients had multiple drainage of the cervical region and mediastinum in combination with pathogen-specific antibiotics. Both recovered without any complications. The third patient probably had inadequate surgical drainage of the mediastinum directly after diagnosis, and died. If the CT scan is suggestive of DNM, the patient should be referred to a thoracic surgical unit immediately. The optimal treatment consists of vigorous surgical drainage of both the neck and mediastinum with irrigation in combination with pathogen-specific antibiotic therapy. An early diagnosis followed by adequate antibiotic and surgical treatment improves the outcome in patients with DNM.

The importance of an organized follow-up for the evaluation of mortality after hospital discharge in cardiac surgery.

OBJECTIVES: Does a structured follow-up, after cardiac surgery in an adult, provide additional information on the operation related mortality especially if mortality is used as an outcome parameter within the quality control? METHOD: Mortality data of 1132 patients undergoing cardiac surgery in 2003 and 2004 in the Academic Hospital Nijmegen, The Netherlands were registered by a structured follow-up one year after surgery. RESULTS: One year after surgery this follow-up is missing information for eight patients (0.7%). Six patients (0.5%) refused further follow-up. Of the 31 patients who died during the first postoperative year, 21 (68%) were registered thanks to this structured follow-up. In 29 patients it was possible to retrieve the cause of death. CONCLUSION: A structured follow-up one year after cardiac surgery has a high response and not only provides a better total picture of mortality, but also information on the cause of death. Both aspects are important if mortality is used as a parameter for quality control in cardiac surgery.