Intra-tumoral vascular or perineural invasion as prognostic factors for long-term survival in early stage non-small cell lung carcinoma

Objective: In recent studies focusing on the prognostic significance of histologic features of NSCLC tumors, vessel invasion was correlated to survival across all surgical stages. We similarly analyzed whether intra-tumoral permeation could affect survival in subgroups of stage I and II NSCLC. Methods: A retrospective single institution analysis of a prospectively computed database. Specimens were analyzed for intra-tumoral vascular, lymphatic and nervous permeation. Overall mortality was determined and for each stage, a Cox regression analysis of selected variables was performed. Detailed histologic information was available in all patients. Follow-up was 100% complete (median = 69 months). Results: From 1989 to 2004, out of 346 patients with stage I and II NSCLC, 253 patients with p stage I (75.7%) and 81 patients with p stage II (24.3%) underwent surgery with complete resection, for a completeness resection rate of 97% (334/346). We performed 70 pneumonectomies, 255 lobectomies and 9 lesser resections (respectively, 21%, 76.3% and 2.7%). In-hospital mortality was 2.1%. The incidence of intra-tumoral permeation was 14.4% (48/334). Permeation correlated both with T status (p = 0.04), grade of differentiation (p = 0.03) and stage (p = 0.02). Median survival and overall 5-year survival for patients with and without permeation were 42.3 months (95% CI [20–64.6]) and 72.1 months (95% CI [56.9–87.2]), respectively; and 44% and 54%, respectively (p = NS). However, intra-tumoral permeation was not a significant predictor for overall death (HR = 1.1 [95% CI = 0.74–1.66). Conclusion: In this large institutional study of early stage NSCLC, the presence of intra-tumoral permeation was correlated both to T, grade of differentiation, as well as to stage. However, in contrast to recent reports, we did not find that intra-tumoral permeation adversely affects long-term survival.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Treatment results of pancoast tumor

To study the clinical characteristics, treatment modalities, and outcome of patients with Pancoast tumors who underwent surgery over 11-year period. From January 1994 to May 2005, 13 patients (12 men, 1 woman) with Pancoast tumor and histology of non-small cell lung cancer underwent surgical resection. Nine patients were received induction therapy (8 chemoradiation, 1 radiation only), and there were no treatment-related deaths. Twelve lobectomies, 1 pneumonectomy, and none of wedge resections or partial resection were performed. The number of ribs resected ranged from 2-6 (median 2.8). Chest wall reconstruction was performed in 2 patients, total vertebrectomy in 2, bronchoplasty in 2, and pulmonary arterioplasty in 1. Twelve of 13 patients (92.3%) had a complete resection. Pathologic stages were IB, IIB, IIIA and IIIB in 1, 7, 2, and 1, respectively, and pathologic complete responses was noted in 1. After a median follow-up of 34 months, the 3-year survival was 78.6% for all 13 patients and 85.7% for patients who had a complete resection. It is thought that induction chemoradiation for Pancoast tumors have potential to be able to become the treatment strategy in the future.     

Prognostic value of FDG uptake in early stage non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) has a poor prognosis even for early stages of the disease (stage I and II). We studied the prognostic value of PET FDG in patients with completely resected stage I and II NSCLC. Methods: Retrospective study of 96 patients with NSCLC whose staging included ¹⁸F-FDG PET (fluoro deoxy glucose positron emission tomography). Histopathological stage was either stage I (75) or stage II (n = 21). FDG uptake was measured as maximal standardized uptake value for body weight (SUVmax). Mean follow-up was 45 ± 30 months (1–142 months). Overall and cancer-free survival rates were recorded. Results: SUVmax were higher for stage II than for stage I (10.5 ± 4.5 vs 8.5 ± 5, p = 0.04). Mean tumor volumes were equivalent for both stages (33 cm³, p = 0.18), excluding a partial volume effect. The median SUVmax in the whole study population was 7.8. The median survival was significantly longer in patients with a lower (SUVmax ≤ 7.8) FDG uptake (127 months vs 69 months, p = 0.001). For stage I tumors (n = 75), high FDG uptake was significantly associated with reduced median survival: 127 months if SUVmax ≤ 7.8 and 69 months if SUVmax > 7.8 (p = 0.001). For stage II tumors (n = 21), no statistical difference was observed: 72 months vs 40 months for SUVmax ≤ 7.8 and for SUVmax > 7.8, respectively (p = 0.11), although there was a clear trend towards reduced survival for highly metabolic tumors. Disease-free survival was also significantly better for lower metabolic tumors: 96.1 months vs 87.7 months (p = 0.01). Conclusion: High FDG uptake is associated with reduced overall survival and disease-free survival of patients with completely resected stage I–II NSCLC. Whether patients with highly metabolic tumors should undergo a closer postoperative surveillance or adjuvant chemotherapy has to be addressed in a properly designed prospective trial.     

The impact of mitral valve surgery combined with maze procedure

Objective: Recent studies indicated that successful maze procedure for atrial fibrillation (AF) adjunct to mitral valve surgery provided a lower incidence of stroke and recurrence of AF. The purpose of this study is to review the 13-year experience of these combined procedures and to identify the risk factors and late outcomes of successful maze procedures compared to failed maze procedures. Methods: At a single institution, 521 consecutive patients underwent combined maze procedures with mitral valve replacements or valvuloplasties. Three kinds of maze techniques were primarily used: Cox–maze III, Kosakai maze, and cryo-maze procedure. Three months after the operation, 394 patients were in sinus rhythm (Group S) while the remaining 116 patients were in continuous or intermittent AF (Group F), excluding 11 early death patients. Risk factors for Group F were determined by the analysis of all patient demographics. Survival, freedom from stroke, cardiac events, and AF recurrence were analyzed. Results: The proportion of the patients without any other simultaneous procedures was greater in Group S (41% vs 29%, P = 0.02). The distributions of mitral valve surgery and maze procedure techniques were similar in these two groups. A left atrium larger than 70 mm [hazard ratio (HR) = 2.6; 95% confidence interval range 1.04–6.3, P = 0.043], preoperative AF history longer than 10 years (HR = 8.2; 4.5–15.1, P < 0.001) and f-wave voltage in V1 smaller than 0.1 mV (HR = 6.2; 5.0–15.2, P < 0.001) were determined to be risk factors for unsuccessful maze procedures. All the results of Cox proportional hazards models showed superiority in Group S; actuarial survival rates (HR = 2.7; 1.04–7.0, P = 0.035), freedoms from stroke (HR = 3.0; 1.1–8.1, P = 0.003) and cardiac events (HR = 4.3; 2.9–6.1, P < 0.001). Freedom from AF recurrence rate was 98.4% at 5 years and 81.0% at 12 years in Group S, and 73.0% and 60.1% in overall patients. Conclusions: Patients with successful maze procedures resulted in higher survival rate, greater freedom from stroke and cardiac events. The large left atrium, small f-wave, and long AF duration were significant risk factors for failed maze procedures, suggesting that earlier surgical interventions would result in superior results in mitral valve surgery combined with maze procedure.     

Accuracy and survival of repeat mediastinoscopy after induction therapy for non-small cell lung cancer in a combined series of 104 patients

Objective: Precise restaging of non-small cell lung cancer after induction therapy is of utmost importance. Remediastinoscopy remains a controversial procedure. In a combined, updated series of two thoracic centres, accuracy and survival of remediastinoscopy were determined. Methods: From November 1994 to August 2005, remediastinoscopy was performed in 104 patients (98 men, 6 women) after induction therapy for locally advanced non-small cell lung cancer. Mean age was 64.3 years (range 38–85). Neoadjuvant chemotherapy was given in 79 patients and chemoradiotherapy in 25. Follow-up data were completed in January 2007. Results: Remediastinoscopy was technically feasible in all patients except for one who died due to perioperative haemorrhage. Remediastinoscopy was positive in 40 patients and negative in 64; the latter group underwent thoracotomy. There were 17 false-negative remediastinoscopies. Sensitivity of remediastinoscopy was 71%, specificity 100% and accuracy 84%. Follow-up was complete for all patients. Sixty-nine died, mostly of distant metastases. Median survival time for the whole group was 18 months (95% confidence interval 11–25). Median survival time in patients with a positive remediastinoscopy was 14 months (95% confidence interval 8–20), with a negative remediastinoscopy 28 months (95% confidence interval 15–41) and with a false-negative remediastinoscopy 24 months (95% confidence interval 3–45). In univariate analysis the difference between positive and negative remediastinoscopies was highly significant (p = 0.001). In a multivariate analysis including sex, age, histology, centre, and nodal status at remediastinoscopy, only nodal status was a significant independent prognostic factor (p = 0.008). Conclusions: Remediastinoscopy is a valuable restaging procedure after induction therapy. Persisting mediastinal nodal involvement proven at remediastinoscopy heralds a poor prognosis.     

The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis

Osteoporosis affects approximately 40–50% of adult patients with β-Thalassemia Major (βTM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of βTM-osteoporosis. OPG/RANKL system acts downstream from IL-1, IL-6 and TNF- and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in βTM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in βTM patients.

IL-1, IL-6 and TNF-, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17β-estradiol, and free-testosterone levels were measured in 30 well treated βTM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients.

βTM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P < 0.0001), decreased osteocalcin (BGP) concentrations (< 0.0001) and significantly lower lumbar (P = 0.001) and femoral (P < 0.05) BMD values as compared to controls. Circulating levels of IL-1 (P < 0.0001), TNF- (P < 0.0001) and IL-6 (P < 0.05) were all increased in βTM patients as compared with controls. In βTM patients, IL-1 was significantly related with D-PYR (r = 0.5; P < 0.05), RANKL (r = 0.7; P = 0.03) and IL-6 (r = 0.3; P = 0.006); IL-6 was also significantly correlated with D-PYR (r = 0.5; P < 0.05) and EPO levels (r = 0.3; P = 0.03); TNF- showed a negative correlation with L2L4 BMD (r = − 0.4; P < 0.05).

Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in βTM-patients, suggesting their involvement in the pathogenesis of βTM-osteoporosis.     

A prospective analysis of the inter-relationship between lung volume reduction surgery and body mass index

Objectives: LVRS is thought to result in significant improvements in BMI. Patients with a higher BMI at the time of diagnosis of COPD are known to have better survival, and those with a low BMI prior to LVRS have significantly worse perioperative morbidity. We aimed to assess the influence of BMI on the outcome of LVRS in our own experience. Methods: Complete preoperative BMI data was available in 114 of 131 consecutive patients who have undergone LVRS since 1995. These patients were arbitrarily classified into three categories: underweight (BMI ≤ 19 kg/m²), normal (BMI 20–25 kg/m²) and overweight (BMI > 26 kg/m²). The in-hospital course and perioperative change in BMI at 3, 6, 12, 24 and 36 months were prospectively recorded for each category and compared. Results: There were no significant differences in preoperative variables except BMI. There were significantly more postoperative ITU admissions among the lowest two BMI groups (12/29, 18/58 and 3/27 patients, respectively, p = 0.02), and significantly shorter hospital stay in overweight patients [16 days (5–79) vs 18 days (6–111) vs 13 days (6–25), respectively, p = 0.005, expressed as median (range)]. However, there was no difference in survival between the three groups (p = 0.21). Postoperative physiological improvements in the first year were related to preoperative BMI for both FEV₁ (r = 0.29, p = 0.02) and DLCO (r = 0.33, p = 0.02). Postoperative BMI significantly increased in the underweight yet significantly decreased in the overweight at all time points. Conclusions: The perioperative course of LVRS and its physiological benefits are influenced by preoperative BMI. Whilst the treatment of the underweight is more complicated, LVRS may be the only way of increasing their BMI. Future work is needed to explore the roles of changing energy requirements and body composition following LVRS.     

Endovascular management of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation

Objective: Whatever the surgical technique used, false aneurysm formation is one of the long-term complications of repair of aortic coarctation. Conservative management is associated with a 100% rate of rupture. The conventional surgical approach is complex and associated with high morbidity and mortality rates. We report our experience of endovascular management of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation. Methods: Between October 2005 and 2006, stent-grafting of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation was performed in four patients. Median age was 31.5 years (range: 24–38). Two patients had undergone two previous interventions. The last previous surgery consisted of graft interposition (N = 2), subclavian flap aortoplasty (N = 1) and aorto-aortic bypass (N = 1). Median size of the pseudo-aneurysm was 31.5 mm (range: 20–58). Mean time between the last surgery and endovascular treatment was 24 years (range: 3–32). One patient was treated emergently because of hemoptysis in relation with an aorto-bronchial fistula, the three other patients were treated electively. A transfemoral approach was used in all patients. The Zenith TX2^® (Cook) thoracic stent-graft was used in all the patients, one patient underwent previous dilatation at the coarctation level. When present, the ostium of the left subclavian artery was always covered (N = 3). Results: No major complication occurred during the procedure and no patient died during the follow-up. One patient presented a type II endoleak which spontaneously healed during the first month. Another patient with his left subclavian artery covered presented claudication of the left arm requiring a carotid-subclavian bypass. After a median follow-up of 7.5 months (range: 1–12.9), the patients were asymptomatic and CT scans demonstrated complete exclusion of all treated postcoarctation aneurysms without recoarctation and without any stent-graft-related complication. Conclusions: The endovascular management of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation is feasible. This approach was safe and effective. Long-term clinic and imaging follow-up is mandatory.     

Fate of pulmonary arteries following Norwood Procedure

Objective: This study evaluated the requirement for surgical reoperation and catheter-based reintervention to central pulmonary arteries (CPAs) following Norwood Procedure (NP). We sought to identify the influence of various surgical techniques employed during NP on subsequent interventions. Methods: Between 1993 and 2004, 226 patients underwent Stage II following NP. Ninety-eight patients (43%) had completion of Fontan circulation (Stage III) and a further 107 (47%) are on course for Fontan completion with 21 (9%) inter-stage deaths. During NP, the aortic arch was reconstructed without additional material (n = 91, 40%) or with a pulmonary homograft patch (n = 135, 60%). Pulmonary blood flow was supplied by modified Blalock–Taussig shunt (n = 177, 78%) or right ventricle to pulmonary artery conduit (RV-PA; n = 49, 22%). The CPAs defect was closed directly (n = 69, 31%) or with a patch (n = 157, 69%). Complete resection of coarctation was performed in 126 patients (56%). Results: Ninety-seven patients (43%) required surgical reoperation to CPAs during Stage II. Actuarial freedom from reoperation was 60 ± 3%, 52 ± 4% and 50 ± 4% at 1, 5 and 10 years, respectively. On multivariable analysis, NP with RV-PA increased risk of reoperation (LR 8.3, 5.3–13.2; p < 0.001). Forty-one patients (18%) required catheter-based reintervention on CPAs. Actuarial freedom from reintervention was 98 ± 1%, 72 ± 4% and 58 ± 6% at 1, 5 and 10 years, respectively. CPA problems were almost exclusively limited to the proximal Left pulmonary artery. On multivariable analysis, catheter-based reintervention became more common with time. Complete resection of coarctation increased risk of reintervention (LR 3.9, 1.6–9.6; p < 0.005). Arch reconstruction and CPAs repair techniques did not affect risk of reoperation or reintervention on CPAs. Conclusions: CPA stenoses and hypoplasia need surgical attention in approximately half of all patients undergoing the NP. The need for reoperation is increased when using the RV-PA conduit technique (although the majority of these are performed as part of the Stage II procedure). Catheter reinterventions are almost exclusively confined to the left CPA and are increased when the arch is shortened by resection of the coarctation tissue at time of NP.     

Retransfusion of pericardial blood does not trigger systemic coagulation during cardiopulmonary bypass

Objective: During cardiopulmonary bypass (CPB), systemic coagulation is believed to become activated by blood contact with the extracorporeal circuit and by retransfusion of pericardial blood. To which extent retransfusion activates systemic coagulation, however, is unknown. We investigated to which extent retransfusion of pericardial blood triggers systemic coagulation during CPB. Methods: Thirteen patients undergoing elective coronary artery bypass grafting surgery were included. Pericardial blood was retransfused into nine patients and retained in four patients. Systemic samples were collected before, during and after CPB, and pericardial samples before retransfusion. Levels of prothrombin fragment F₁₊₂ (ELISA), microparticles (flow cytometry) and non-cell bound (soluble) tissue factor (sTF; ELISA) were determined. Results: Compared to systemic blood, pericardial blood contained elevated levels of F₁₊₂, microparticles and sTF. During CPB, systemic levels of F₁₊₂ increased from 0.28 (0.25–0.37; median, interquartile range) to 1.10 (0.49–1.55) nmol/l (p = 0.001). This observed increase was similar to the estimated (calculated) increase (p = 0.424), and differed significantly between retransfused and non-retransfused patients (1.12 nmol/l vs 0.02 nmol/l, p = 0.001). Also, the observed systemic increases of platelet- and erythrocyte-derived microparticles and sTF were in line with predicted increases (p = 0.868, p = 0.778 and p = 0.205, respectively). Before neutralization of heparin, microparticles and other coagulant phospholipids decreased from 464 μg/ml (287–701) to 163 μg/ml (121–389) in retransfused patients (p = 0.001), indicating rapid clearance after retransfusion. Conclusion: Retransfusion of pericardial blood does not activate systemic coagulation under heparinization. The observed increases in systemic levels of F₁₊₂, microparticles and sTF during CPB are explained by dilution of retransfused pericardial blood.     

Jugular venous valved conduit (Contegra) matches allograft performance in infant truncus arteriosus repair

Objective: Limited availability and durability of allograft conduits require that alternatives be considered. We compared bovine jugular venous valved (JVV) and allograft conduit performance in 107 infants who survived truncus arteriosus repair. Methods: Children were prospectively recruited between 2003 and 2007 from 17 institutions. The median z-score for JVV (n = 27, all 12 mm) was +2.1 (range +1.2 to +3.2) and allograft (n = 80, 9–15 mm) was +1.7 (range −0.4 to +3.6). Propensity-adjusted comparison of conduit survival was undertaken using parametric risk-hazard analysis and competing risks techniques. All available echocardiograms (n = 745) were used to model deterioration of conduit function in regression equations adjusted for repeated measures. Results: Overall conduit survival was 64 ± 9% at 3 years. Conduit replacement was for conduit stenosis (n = 16) and/or pulmonary artery stenosis (n = 18) or regurgitation (n = 1). The propensity-adjusted 3-year freedom from replacement for in-conduit stenosis was 96 ± 4% for JVV and 69 ± 8% for allograft (p = 0.05). The risk of intervention or replacement for branch pulmonary artery stenosis was similar for JVV and allograft. Smaller conduit z-score predicted poor conduit performance (p < 0.01) with best outcome between +1 and +3. Although JVV conduits were a uniform diameter, their z-score more consistently matched this ideal. JVV exhibited a non-significant trend towards slower progression of conduit regurgitation and peak right ventricular outflow tract (RVOT) gradient. In addition, catheter intervention was more successful at slowing subsequent gradient progression in children with JVV versus those with allograft (p < 0.01). Conclusions: JVV does match allograft performance and may be advantageous. It is an appropriate first choice for repair of truncus arteriosus, and perhaps other small infants requiring RVOT reconstruction.     

Quality assessment of distal SAS connector anastomosis by 13 MHz epicardial ultrasound

Objective: During application of a distal coronary bypass connector, we employed 13 MHz epicardial ultrasound to evaluate quantitative caliper measurements for vessel size matching and to assess anastomosis quality after connector deployment. Methods: Two S²AS connector anastomoses were constructed on ex vivo pressure-perfused porcine hearts. Epicardial ultrasound measurements of the connector ring and anastomosis were compared to intravascular ultrasound measurement and cast dimensions. In 21 pigs, anastomotic sites with internal diameter of 2.25–3.0 mm (internal mammary artery, IMA) and 1.8–2.2 mm (left anterior descending coronary artery, LAD) were selected using external caliper and epicardial ultrasound measurements. Anastomoses were visualized and assessed intraoperatively (beating heart, n = 21) and at 3 and 6 months’ follow-up (explanted heart, n = 10 each). Results: Epicardial ultrasound underestimated connector dimension by ≤5% versus intravascular ultrasound and deviated ≤13% from cast dimensions for other anastomotic measurements. Caliper estimates of internal IMA and LAD diameter differed from ultrasound by −3 ± 6% and −2 ± 7% (mean ± SD), respectively. Intraoperatively, the anastomotic orifice was flawless in all animals. It remained fully patent at 3 and 6 months by ultrasound, which was confirmed by histology. The connector to LAD percentage diameter stenosis changed from −12 ± 5% intraoperatively to −1 ± 7% at 3 months and from −5 ± 6% intraoperatively to −16 ± 13% at 6 months, in the growing pig model. Conclusions: In the pig, external caliper measurements provided a reliable quantitative estimate of inner graft and coronary diameter for connector size matching. Epicardial 13 MHz ultrasound is a promising method to assess coronary anastomosis quality even when connector metal is present.     

A Pilot Study of Body Composition and Bone Mineral Density in Healthy Men From Argentina

A precise assessment of bone mineral density (BMD) and body composition can be performed using dual-energy X-ray absorptiometry (DXA). Values of body composition for males would be useful to evaluate the occurrence of alterations in body composition in a number of diseases. The objectives of this study were to establish BMD and body composition values in healthy men and to analyze age-related changes. BMD and body composition of total body and subareas were determined in 116 healthy men (aged 20–79 yr) using DXA. Comparison between 20–29- and 70–79-yr-old men showed that older subjects were shorter (p < 0.03), and had a higher body mass index (p < 0.01). Fat mass increased (+46.7%; p < 0.001) especially in the trunk. Lean mass (LM) decreased (−9.4%; p < 0.05) mainly in the arms and legs. Bone mineral content (BMC) and BMD decreased (−15.3% [p < 0.001], −6.3% [p < 0.05], respectively). Correlation was observed between BMC and LM (r = 0.7, p < 0.01). Values of BMD and body composition in healthy men were obtained. A relation was observed between bone mass and body composition, suggesting that the age-related decrease in LM may be associated to bone mass loss. Further studies should be conducted to elucidate the role of body composition in the occurrence of osteoporosis in men.     

Determinants of Changes in Bone Density: A 5-Year Follow-Up Study of Adult Male Monozygotic Twins

The relative importance of determinants in bone mineral density (BMD) in adult men is partly unclear. Our goals were to investigate the effects of familial aggregation and behavioral factors on the change in BMD during a 5-yr follow-up. Subjects (n = 140) were 70 exposure-discordant monozygotic twin pairs (age 35–69 yr). BMD was measured with the same dual-energy X-ray absorptiometry scanner at baseline and at the 5-yr follow-up. A variety of covariates were used including physical examination and interview data. Multivariate linear regression was used. The mean annual decrease in femoral BMD was 0.2%. The mean lumbar BMD was unchanged, although 8–17% of subjects had a decrease of more than 5%. Familial aggregation explained 14% of the changes in femoral BMD and 19% in lumbar BMD. The stability of BMD in the follow-up was high, both for individuals (intraclass correlation coefficient [ICC] = 0.90–0.94) and for co-twins in a pair (ICC = 0.77–0.84). In femoral BMD, use of alcohol (p = 0.006), coffee (p = 0.046), and beta-blockers (p = 0.043) led to increases, whereas smoking led to a decrease (p < 0.01). We concluded that frequent increases in BMD, influenced by beta-blockers, partly explain the minor mean changes during follow-up; however, about every 10th subject had a significant decrease. Overall, familial effects played a dominant role in BMD changes in adult men.     

Comparison of on pump and off pump coronary surgery: risk factors for neurological outcome

Objective: Cerebrovascular accidents (CVA) are devastating complications after coronary artery bypass grafting (CABG). The reported incidence of neurological complications after conventional CABG (CCABG) is 3–6%. Off-pump coronary bypass grafting (OPCAB) has been associated in recent studies to a decreased morbidity and risk of perioperative stroke. Nevertheless, uncertainty still surrounds the relative benefits of OPCAB. We investigated whether, in our experience, OPCAB was associated with lower neurological morbidity than conventional CABG approach. Methods: Eight thousand and two patients underwent isolated CABG at our institution between January 1998 and January 2005. OPCAB operation was performed on 1415 patients. Data were prospectively collected. A multiple logistic regression analysis was used to evaluate the influence of the two different surgical techniques on the neurological outcomes. Results: Patients in the OPCAB group were significantly older (66.2 vs 63.5%, p < 0.0001), had a higher incidence of renal injury (5.4 vs 2.4%, p < 0.0001), and were more redo interventions (6.95 vs 1.53%, p < 0.0001). The CCABG patients were more urgent at operation (5.46 vs 3.26, p = 0.0007), were less hypertensive (57.6 vs 63% of the patients, p = 0.0003) more diabetics (22 vs 20.6%, NS), and had an ejection fraction less than 0.40 (10.4 vs 9.6%, NS). CVA incidence was similar in both groups (Type I outcome: OPCAB = 0.70% vs CCABG = 0.68%, p = 0.91; Type II outcome OPCAB = 0.70% vs CCABG = 0.83%, p = 0.63). Conclusions: In our experience patients undergoing CCABG were not exposed to a grater risk of neurological adverse events when compared to OPCAB patients.     

Risk factors for reoperation after relief of congenital subaortic stenosis

Background: Congenital subaortic stenosis entails a lesion spectrum, ranging from an isolated obstructive membrane, to complex tunnel narrowing of the left outflow associated with other cardiac defects. We review our experience with this anomaly, and analyze risk factors leading to restenosis requiring reoperation. Methods: From 1994 to 2006, 58 children (median age 4.3 years, range 7 days–13.7 years) underwent primary relief of subaortic stenosis. Patients were divided into simple lesions (n = 43) or complex stenosis (n = 15) associated with other major cardiac defects. Age, pre- and postoperative gradient over the left outflow, associated aortic or mitral valve insufficiency, chromosomal anomalies, arteria lusoria, and operative technique (membrane resection (22) vs associated myectomy (34) vs Konno (2)) were analyzed as risk factors for reoperation (Kaplan–Meier, Cox regression). Results: There was no operative mortality. Median follow-up spanned 2.7 years (range 0.1–10), with one late death at 4 months. Reoperation was required for recurrent stenosis in 11 patients (19%) at 2.6 years (range 0.3–7.5) after initial surgery. Risk factors for reoperation included complex subaortic stenosis (p = 0.003), younger age (p = 0.012), postoperative residual gradient (p = 0.019), and the presence of an arteria lusoria (p = 0.014). For simple lesions, no variable achieved significance for stenosis recurrence. Conclusions: Surgical relief of congenital subaortic stenosis, even with complex defects, yields excellent results. Reoperation is not infrequent, and should be anticipated with younger age at operation, complex defects, residual postoperative gradient, and an arteria lusoria. Myectomy concomitant to membrane resection, even in simple lesions, does not provide enhanced freedom from reoperation, and should be tailored to anatomic findings.     

Pulmonary lactate release following cardiopulmonary bypass

Objective: The etiology of lung injury following cardiopulmonary bypass (CPB) is multifactorial. Our study focused on quantifying the lactate release from the lungs precipitated by extracorporeal circulation at different time points after the insult. This was complemented by an evaluation of the gas exchange at the level of the alveolar–capillary membrane. Methods: Forty consecutive patients (age 61 ± 11 years, EuroScore 4.7 ± 2.7) undergoing CABG were prospectively analyzed. The data are presented as medians and the interquartile range. Results: The pulmonary lactate release (PLR) increased from a baseline value of 0.033 (range −0.077 to 0.170) to 0.465 mmol/min/m² (range 0.113–0.922), which was seen 6 h postoperatively (P < 0.001). The A-a O₂ gradient increased from 12.7 (range 8.8–15) to 39.1 kPa (range 30.3–46.5) upon discontinuation of CPB (P < 0.001). The systemic arterial lactate (L_S) concentration increased from 1.22 (range 1–1.44) to 3.03 mmol/l (range 2.29–4.76) 6 h after surgery (P < 0.001). The veno-arterial pCO₂ difference (V-A dpCO₂) rose from 0.6 (range 0.5–0.9) to 0.9 kPa (range 0.7–1) (P = 0.014). The mortality in the studied group was 5% (2/40). Conclusions: The lungs were found to be a significant source of lactate, and this pulmonary lactate flux was accentuated by CPB. The PLR correlated with systemic hyperlactatemia as well as the A-a O₂ gradient, and was found to be higher in patients requiring prolonged mechanical ventilatory support. The duration of CPB had a significant impact on the systemic lactate concentrations, V-A dpCO₂ and the A-a O₂ gradient, but not on the PLR.     

Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study

A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or cobalamin, which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism. We examined the association between intake of Hcy-related B vitamin (riboflavin, pyridoxine, folate and cobalamin) and femoral neck bone mineral density BMD (FN-BMD) and the risk of fracture in a large population-based cohort of elderly Caucasians.

We studied 5304 individuals aged 55 years and over from the Rotterdam Study. Dietary intake of nutrients was obtained from food frequency questionnaires. Incident non-vertebral fractures were recorded during a mean follow-up period of 7.4 years, and vertebral fractures were assessed by X-rays during a mean follow-up period of 6.4 years. We observed a small but significant positive association between dietary pyridoxine (β = 0.09, p = 1 × 10^− 8) and riboflavin intake (β = 0.06, p = 0.002) and baseline FN-BMD. In addition, after controlling for gender, age and BMI, pyridoxine intake was inversely correlated to fracture risk. As compared to the three lowest quartiles, individuals in the highest quartile of age- and energy-adjusted dietary pyridoxine intake had a decreased risk of non-vertebral fractures (HR = 0.77, 95% CI = 0.65–0.92, p = 0.005) and of fragility fractures (HR = 0.55, 95% CI = 0.40–0.77, p = 0.0004). Further adjustments for other dietary B vitamins (riboflavin, folate and cobalamin), dietary intake of calcium, vitamin D, vitamin A and vitamin K, protein and energy intake, smoking and BMD did not essentially modify these results.

We conclude that increased dietary riboflavin and pyridoxine intake was associated with higher FN-BMD. Furthermore, we found a reduction in risk of fracture in relation to dietary pyridoxine intake independent of BMD. These findings highlight the importance of considering nutritional factors in epidemiological studies of osteoporosis and fractures.