An initial evaluation of post-cardiopulmonary bypass acute kidney injury in swine

Objective: Acute kidney injury (AKI) post-cardiac surgery is associated with mortality rates approaching 20%. The development of effective treatments is hindered by the poor homology between rodent models, the mainstay of research into AKI, and that which occurs in humans. This pilot study aims to characterise post-cardiopulmonary bypass (CPB) AKI in an animal model with potentially greater homology to cardiac surgery patients. Methods and results: Adult pigs, weighing 50–75 kg, underwent 2.5 h of CPB. Pigs undergoing saphenous vein grafting procedures served as controls. Pre-CPB measures of porcine renal function were within normal ranges for adult humans. The effect of CPB on renal function; a 25% reduction in ⁵¹Cr-EDTA clearance (p = 0.068), and a 33% reduction in creatinine clearance (p = 0.043), was similar to those reported in clinical studies. CPB resulted in tubular epithelial injury (median NAG/creatinine ratio 2.6 u mmol⁻¹ (interquartile range (IQR): 0.81–5.43) post-CPB vs 0.48 u mmol⁻¹ (IQR: 0.37–0.97) pre-CPB, p = 0.043) as well as glomerular and/or proximal tubular injury (median albumin/creatinine ratio 6.8 mg mmol⁻¹ (IQR: 5.45–13.06) post-CPB vs 1.10 mg mmol⁻¹ (IQR: 0.05–2.00) pre-CPB, p = 0.080). Tubular injury scores were significantly higher in kidneys post-CPB (median score 2.0 (IQR: 1.0–2.0) relative to vein graft controls (median score 1.0 (IQR 1.0–1.0), p = 0.019). AKI was associated with endothelial injury and activation, as demonstrated by reduced DBA (dolichos biflorus agglutinin) lectin and increased endothelin-1 and vascular cell adhesion molecule (VCAM) staining. Conclusions: The porcine model of post-CPB AKI shows significant homology to AKI in cardiac surgical patients. It links functional, urinary and histological measures of kidney injury and may offer novel insights into the mechanisms underlying post-CPB AKI.     

Intra-aortic balloon pump-induced pulsatile flow reduces coagulative and fibrinolytic response to cardiopulmonary bypass

Abstract:  The aim of this study is to evaluate if a simple intra-aortic balloon pump (IABP)-induced pulsatile perfusion reduces activation of coagulative system during cardiopulmonary bypass (CPB). Ninety-six patients undergoing preoperative IABP were randomized to nonpulsatile CPB with IABP discontinued during cardioplegic arrest (Group A) or IABP-induced pulsatile CPB (Group B). White blood cells (WBC), hematocrit (Ht), platelets (PLTs), International Normalized Ratio (INR), fibrinogen, activated partial thromboplastin time (aPTT), antithrombin III (AT-III) activity, and D-dimer were measured at the end of surgery (ES) and postoperatively. Chest drainage, need for reexploration, and transfusions were compared. Group B showed lower chest drainage (1st day P  = 0.038; 2nd day P  = 0.044), transfusions ( P  = 0.031), WBC ( P  < 0.05 at all time points), and INR ( P  < 0.05 at all time points), together with a higher Ht ( P  < 0.05 at ES, 12 h), platelets ( P  < 0.04 at all time points), fibrinogen ( P  < 0.05 at ES, 12 h, 24 h), and aPTT ( P  < 0.05 at all time points). AT-III activity lowered in Group A ( P  = 0.001 at ES, 12 h, 24 h), together with higher D-dimer levels ( P  < 0.05 at all time points). IABP-induced pulsatile perfusion ameliorates coagulative system activation following CPB.     

Brain preservation with selective cerebral perfusion for operations requiring circulatory arrest: protection at 25 °C is similar to 18 °C with shorter operating times

Background: Hypothermic circulatory arrest (HCA) is employed for aortic arch and other complex operations, often with selective cerebral perfusion (SCP). Our previous work has demonstrated real-time evidence of improved brain protection using SCP at 18 °C. The purpose of this study was to evaluate the utility of SCP at warmer temperatures (25 °C) and its impact on operating times. Methods: Piglets undergoing cardiopulmonary bypass (CPB) and 60 min of HCA were assigned to three groups: 18 °C without SCP, 18 °C with SCP and 25 °C with SCP (n = 8 animals per group). CPB flows were 100 ml kg⁻¹ min⁻¹ using pH-stat management. SCP flows were 10 ml kg⁻¹ min⁻¹ via the innominate artery. Cerebral oxygenation was monitored using NIRS (near-infrared spectroscopy). A microdialysis probe placed into the cerebral cortex had samples collected every 15 min. Animals were recovered for 4 h after separation from CPB. All data are presented as mean ± standard deviation (SD; p < 0.05, significant). Results: Cerebral oxygenation was preserved during deep and tepid HCA with SCP, in contrast to deep HCA without SCP (p < 0.05). Deep HCA at 18 °C without SCP resulted in significantly elevated brain lactate (p < 0.01) and glycerol (p < 0.01), while the energy substrates glucose (p < 0.001) and pyruvate (p < 0.001) were significantly depleted. These derangements were prevented with SCP at 18 °C and 25 °C. The lactate/pyruvate ratio (L/P) was profoundly elevated following HCA alone (p < 0.001) and remained persistently elevated throughout recovery (p < 0.05). Piglets given SCP during HCA at 18 °C and 25 °C maintained baseline L/P ratios. Mean operating times were significantly shorter in the 25 °C group compared to both 18 °C groups (p < 0.05) without evidence of significant acidemia. Conclusion: HCA results in cerebral hypoxia, energy depletion and ischaemic injury, which are attenuated with the use of SCP at both 18 °C and 25 °C. Procedures performed at 25 °C had significantly shorter operating times while preserving end organs.     

Role of fluorine-flurodeoxyglucose positron emission tomography/computed tomography in preoperative assessment of anterior mediastinal masses

Objective: The purpose of the study was to explore the usefulness of fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) in the preoperative assessment of isolated anterior mediastinal lesions, especially in the planning of operative strategy (biopsy or upfront resection). Methods: During the last 36 months, 19 consecutive patients (10 males, mean age 54 ± 16 years) underwent PET-CT in the preoperative work-up of isolated anterior mediastinal diseases. Maximal transverse diameter at CT and the postoperative histology and Masaoka staging for thymomas were collected and related to the maximum standardised uptake values (SUVs). Thymomas were divided into low-risk thymoma (LRT = A, AB and B1) and high-risk thymoma (HRT = B2, B3 and C). Results: There were 13 thymomas (six LRT and seven HRT), three lymphomas and three other primitive thymic tumours (one paraganglioma, two non-seminomatous germ cell tumours). In LRT, the mean SUV was 3.3 ± 0.5 resulting significantly lower than HRT, 13.5 ± 7 (p = 0.009). The SUV in LRT was also significantly lower with respect to lymphoma, 12.4 ± 4 (p = 0.001), and the other primitive anterior mediastinal tumours, 8 ± 0.8 (p = 0.001). Between thymomas we found a significant correlation between Masaoka stage and SUV, r = 0.718, p = 0.006. No correlation was found between transverse diameters and SUV, r = 0.141, p = 0.6. Conclusions: In our experience, low SUV (<5) is associated with LRT and minimal invasive thymoma (Masaoka stages I–II) and, therefore, susceptible to upfront surgery. For lesions with an infiltrative aspect on CT scan associated with a higher SUV (>5), an open biopsy is mandatory to exclude mediastinal lymphomas or, in case of HRT, to address a neoadjuvant treatment.     

Short-term systolic and diastolic ventricular performance after surgical ventricular restoration for dilated ischemic cardiomyopathy

Objective: Based on the adverse relationship between left ventricular (LV) remodeling and clinical outcome in ischemic cardiomyopathy, surgical ventricular restoration (SVR) is proposed as a valuable adjunct procedure. This study reports on the short-term clinical and hemodynamical performance of SVR. Methods: Using end-systolic LV volume as indication for SVR, 78 patients with ischemic cardiomyopathy are divided in two groups: group 1 comprised 55 patients treated by coronary revascularization and mitral annuloplasty, group 2 comprised 23 patients undergoing additional SVR. Hemodynamic investigation included echocardiographic assessment of systolic and diastolic function. Clinical follow-up focused on survival and functional status with exercise performance. Results: Both surgical approaches resulted in improvement of NYHA class (2.9–1.6 in group 1; 3.3–1.5 in group 2, p < 0.001), achieving similar exercise performance (peak VO₂ 13.7 vs 15.4 ml/kg min in groups 1 and 2, p = 0.25) and plasma BNP values (group 1: 1350 pg/ml and group 2: 767 pg/ml, p = 0.23). SVR provided additional benefit as patients basically had a worse NYHA class (2.9 in group 1 vs 3.3 in group 2, p = 0.03). Within mean follow-up of 20 months, survival rate was 84% in group 1 and 74% in group 2 (p = 0.11), including operative mortality of 7% and 13% (p = 0.42). Through effective volume reduction (LVEDVI 41%; LVESVI 49%) systolic function improved immediately after SVR (LVEF 27–39% in group 2, p < 0.05). Worsening of diastolic function was specifically observed after SVR within the first year (E/A-ratio 1.38–1.74 cm/s, p = 0.02). Recurrent mitral regurgitation (p = 0.004) and secondary remodeling (p = 0.01) were major determinants of decreasing LV compliance. Clinical outcome in terms of cardiac events and survival was compromised by restrictive diastolic function (p = 0.02) and increased LV volumes (p = 0.04). Conclusion: SVR in addition to coronary revascularization and restrictive mitral annuloplasty results in significant clinical improvement in selected patients with advanced ischemic heart disease and severely dilated ventricles. SVR entails immediate improvement of systolic function, which remains sustained during short-term follow-up. Serial assessment of diastolic function is mandatory as LV compliance seems more sensitive to early changes induced by recurrence of mitral regurgitation and secondary ventricular dilation. Moreover, worsening of diastolic dysfunction should be timely recognized because of its adverse clinical impact.     

Coronary artery bypass grafting with concomitant cardiac resynchronisation therapy in patients with ischaemic heart failure and left ventricular dyssynchrony

Objective: We have tested the hypothesis that epicardial implantation of cardiac resynchronisation therapy (CRT) system during coronary artery bypass grafting (CABG) may be an additional treatment method, which can decrease the mortality and improve left ventricle (LV) systolic function in patients with ischaemic heart failure (HF) and LV dyssynchrony. Methods: One hundred and seventy-eight consecutive patients with severe ischaemic HF and LV dyssynchrony were enrolled in two groups: CABG alone (n = 87) and epicardial CRT implantation during CABG (n = 91). The primary end point of the study was the comparison of mortality between two groups at 18 months of follow-up. Results: Twenty-three patients (26.1%) in the CABG group died at 18 months of follow-up compared with nine (10%) in CABG + CRT group (log-rank test, p = 0.006). The Cox regression analysis revealed that LV dyssynchrony (hazard ratio (HR) 2.634 (1.206–5.751), p = 0.015) was the independent predictor of all-cause death and HF hospitalisation. LV systolic function, dyssynchrony signs and quality of life did not change significantly post-CABG compared to pre-CABG data in CABG group patients. On the contrary, echocardiography revealed an improved LV ejection fraction (42 ± 1.9 vs 28 ± 2.7; p < 0.001), smaller LV end-systolic volume (120 ± 57.5 vs 164 ± 61.4; p = 0.04) and improved LV synchrony in the CABG + CRT group compared with the CABG group. In the CABG + CRT group, more patients improved by two NYHA classes (NYHA, New York Heart Association; 49 vs 0; p = 0.028), had a longer 6-min-walk test distance (452 ± 65 vs 289 ± 72; p < 0.001) and a better quality of life (22.9 ± 5 vs 46.4 ± 11; p < 0.001) compared with the CABG group. Conclusion: For majority of the patients with ischaemic HF and evidence of LV dyssynchrony, CABG neither eliminates dyssynchrony nor improves systolic function. Epicardial implantation of a CRT system concomitant with CABG facilitates patient management in the early postoperative period, improves LV systolic function and quality of life and is associated with low mortality at 18 months of follow-up.     

Anxiety during the COVID-19 pandemic in prisoners who had high risks to suffer from mood disorders: A longitudinal study before and during the COVID-19

We compared the anxiety levels in prisoners before and after the COVID-19 outbreak and analyzed the causes of the changes in anxiety. The first survey was conducted in October 2019 (T0), and the second was conducted in March 2020 (T1). Generalized anxiety disorder-7 (GAD-7), Patient Health Questionnaire-9, and Insomnia Severity Index scales were selected to assess the quality of emotion and sleep among prisoners (N = 803). Three subjective questions were asked to evaluate prisoners' personal feelings on the COVID-19. Paired Samples T-test, Binary, and Multivariate Logistic Stepwise Regression were used to analyze the data. GAD-7 scores decreased at T1 (p < 0.001). For the prisoners without anxiety at T0 (n = 480), GAD-7's mean value at T1 raised (p < 0.001), whereas the mean value decreased (p < 0.001) for the prisoners with anxiety at T0 (n = 323). For the prisoners without anxiety, shorter years of education (OR = 0.843), COVID-19 (OR = 4.936), severer depression at T1 (OR = 1.683), and severer insomnia at T1 (OR = 1.134) were associated with the new onset of anxiety. For the prisoners with anxiety, anxiety was alleviated in 71.2% and exacerbated in 10.5% at T1. For the alleviators, severer depression at T1 (OR = 0.667) and COVID-19 (OR = 0.258) were associated with anxiety unrelief; severer anxiety at T0 (OR = 1.343) was associated with anxiety alleviation. For the exacerbators, severer anxiety at T0 (OR = 0.517) was associated with anxiety unaggravation; severer depression at T1 (OR = 1.196), COVID-19 (OR = 22.882), and severer depression at T0 (OR = 1.181) were associated with anxiety exacerbation. At the outbreak of COVID-19, prisoners' anxiety was reduced. The main factor was the baseline anxiety levels. That may be related to prison management and the Downward Social Comparison.     

SAPS 3 at dialysis commencement is predictive of hospital mortality in patients supported by extracorporeal membrane oxygenation and acute dialysis

Objective: This study examined the association between hospital mortality and five illness–severity scoring systems evaluated at different time points in the intensive care unit (ICU) as well as clinical variables as predictors in critically ill patients supported by extracorporeal membrane oxygenation (ECMO) and acute dialysis. Methods: This multicenter prospective observational study included 104 patients who received ECMO support and acute dialysis from January 2002 to December 2006. Patients’ demographic, clinical and laboratory variables were analyzed as predictors of survival. The SAPS 2, APACHE II, SOFA, MODS, and SAPS 3 scores upon ICU admission and at acute dialysis commencement were evaluated to predict the patient's hospital mortality. Results: Hospital mortality for the study group was 76% (79/104). Among the five scoring systems, only SAPS 3 score showed a significant difference between survivors and non-survivors either upon ICU admission (p = 0.038) or at dialysis commencement (p = 0.001). SAPS 3 score at dialysis commencement showed the best discrimination ability by using the area under the receiver operating characteristic curve (SOFA, 0.55; SAPS 2, 0.56; MODS, 0.58; APACHE II, 0.59; and SAPS 3, 0.73). Multiple logistic regression analysis indicated that SAPS 3 score at dialysis commencement (OR: 1.070, 95% CI: 1.016–1.216) and IABP usage before ECMO (OR: 4.181, 95% CI: 1.448–12.075) were two independent risk factors for hospital mortality. Conclusions: Among five common ICU scoring systems evaluated at different time points, SAPS 3 at dialysis commencement is the best risk adjustment systems to predict hospital mortality in critically ill patients supported by ECMO and acute dialysis. Furthermore, the SAPS 3 score at dialysis commencement and IABP usage before ECMO are two major independent predictors for hospital mortality in patients supported by ECMO and acute dialysis.     

Quality of life evolution after lung cancer surgery in septuagenarians: a prospective study

Objective: To prospectively evaluate quality of life (QoL) evolution after lung cancer surgery in a cohort of septuagenarians with the European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire-C30 and LC13. Methods: Between January 2003 and December 2006, QoL was prospectively recorded in 60 consecutive septuagenarians undergoing lung cancer surgery. Forty-nine lobectomies and 11 pneumonectomies were performed. Questionnaires were administered before surgery and 1, 3, 6 and 12 months postoperatively (MPO) with response rates of 100%, 83%, 87%, 90% and 77%, respectively. Results: After lobectomy, QoL scores returned to baseline 3–6 months after surgery, with the exception of a persistent decrease in physical functioning and an increase in dyspnea within the 12 months follow-up. In the 12 months follow-up period after pneumonectomy, there was no return to baseline in physical, role and social functioning. After pneumonectomy, most quality of life scores returned to baseline at 1-month follow-up, with the exception of dyspnea and general pain, which returned to baseline at 3 and 6 months, respectively. Comparing both resections, significant differences in evolution of physical functioning (6MPO p = 0.045), role functioning (3MPO p = 0.035), social functioning (6MPO p = 0.006, 12MPO p = 0.001) and general pain (6MPO p = 0.037) were reported in favor of lobectomy. Conclusions: The present study documented QoL evolution profiles of septuagenarians after pulmonary surgery. The results indicate that both resections have a major impact on elderly patients, especially physical functioning and dyspnea status. If both resections are compared, lobectomy patients have a more favorable evolution in QoL subscales compared to pneumonectomy.     

Is tricuspid valve replacement a catastrophic operation?

Objective: Tricuspid valve replacement (TVR) has a high postoperative mortality, despite recent advances in perioperative care. We report the results of our experience in TVR with an emphasis on early mortality and morbidity and long-term follow-up. Methods: Between October 1994 and August 2007, 80 consecutive TVRs were performed in 78 patients. The mean age was 48 ± 14 (range: 20–70) years. The underlying disease of the patients was classified as rheumatic (n = 54), congenital (n = 12), endocarditis (n = 10) or degenerative (n = 4). Previous cardiac surgery had been performed in 40 patients (50%). Isolated TVR was performed in 24 patients (30%). Results: Hospital mortality occurred in one patient (1.4%). Postoperative morbidities included intra-aortic balloon pump (n = 5), bleeding re-operation (n = 4), delayed sternal closure (n = 3), acute renal failure (n = 3), subdural haematoma (n = 3), extracorporeal membrane oxygenation (n = 1), mediastinitis (n = 1) and pacemaker insertion (n = 4). In 42 patients, ventilator support was needed for more than 72 h. Based on multivariate analysis, age (p < 0.001) and the cardiopulmonary time (p = 0.004) were the identified risk factors. Follow-up was completed in all patients with a mean duration of 56 ± 37 (range: 0–158) months. During the follow-up period, there were seven deaths (8.8%), including five cardiac deaths. The 5- and 8-year survival rates were 95 ± 3% and 79 ± 9% and event-free survival rates were 76 ± 6% and 61 ± 9%, respectively. Based on multivariate analysis, the only identified predictors of late deaths was a postoperative low cardiac output (p = 0.024). Conclusions: TVR can be performed and low operative mortality can be achieved thorough optimal perioperative management in the current era.     

Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20–34

Background  A group of patients with type 2 diabetes mellitus (T2DM) and body mass index (BMI) 20–34 kg/m² were submitted to laparoscopic interposition of a segment of ileum into the proximal jejunum or into the proximal duodenum associated to a sleeve gastrectomy. The objective of this study is to evaluate the hormonal changes in the pre- and postoperative period. Materials and methods  Hormonal evaluation was done in 58 patients operated between April 2005 and July 2006. Mean age was 51.4 years (40–66 years). Mean BMI was 28.2 (20–34.8) kg/m². All patients had had the diagnosis of T2DM for at least 3 years. Mean duration of T2DM was 9.6 years (3–22 years). Two techniques were performed, consisting of different combinations of ileal interposition (II) associated to a sleeve gastrectomy (SG). The following hormones were assayed in the pre- and postoperative period (mean 16 months) at the baseline and following specific food stimulation (30, 60, 120 min): glucogen-like protein 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), insulin, glucagon, C-peptide, amylin, colecystokinin (CCK), pancreatic polypeptide (PPP), somatostatin, peptide YY (PYY), ghrelin, adiponectin, resistin, leptin, and interleukin-6 (IL-6). Results  Thirty patients had II associated to sleeve gastrectomy (II-SG) and 28 had II with diverted sleeve gastrectomy (II-DSG). GLP1 exhibited an important rise following the two operations, especially after II-DSG (p < 0.001). GIP also exhibited an important rise, with both II-SG and II-DSG being equally effective (p < 0.001). Insulin and amylin showed a significant rise at 30 min. Glucagon decreased slightly. CCK measurements were very low after II-DSG. PPP was also slightly altered by the II-DSG. PYY showed an important increase with both operations (p < 0.001). Ghrelin showed a significant decrease following the two operations (p < 0.001).Somatostatin and IL-6 were not affected (p = 0.632). Both leptin and resistin blood levels decreased. Adiponectin showed a slight increase. Mean postoperative follow-up was 19.2 months. Both II-SG and II-DSG were effective in achieving adequate glycemic control (91.2%). Conclusions  There was a significant hormonal change following laparoscopic ileal interposition. These alterations may explain the promising good results associated to these operations for the treatment of T2DM in the nonmorbidly obese population.     

A short 4-cm oesophageal myotomy relieves the obstructive symptoms of achalasia

Objective: Controversy still persists regarding the ideal length of myotomy to treat oesophageal achalasia. This investigation reports the effects of a short myotomy with an added partial fundoplication for reflux prevention. Methods: From 1997 to 2007, 22 patients (13 men, 9 women, median age: 41 years) with achalasia underwent a 6-cm short myotomy (four oesophagus and two stomach) with a Belsey partial fundoplication by left thoracotomy. Assessments include clinical and radiological evaluation, radionuclide transit studies, manometry, 24-h pH and endoscopy. Results: No morbidity and no mortality occurred. Median follow-up is 54 months (range: 4–139 months). Dysphagia present in all 22 patients left an episodic slow emptying sensation in three patients after operation (p < 0.001). Fresh food regurgitation decreased significantly after the myotomy (17 pre-, four post-regurgitation, p < 0.001). Heartburn present in four patients before the operation was recorded in nine patients postoperatively (p = 0.179). Radiologically, barium stasis decreased significantly from 85% to 30% (p = 0.007). No diverticular formation was seen in the myotomy zone. On the oesophageal scintigram, stasis at 2 min decreased from a median of 60% before the operation to 16% (p < 0.001). The lower oesophageal sphincter (LOS) gradient decreased from 30 to 9.7 mmHg (p < 0.001). LOS relaxation improved from 40% pre- to 93% postoperatively (p = 0.003). Endoscopies and biopsies documented increased mucosal damage after the operation (one preoperative, 13 postoperative; p < 0.001). Conclusions: When treating achalasia, the myotomy, despite being shortened in length, reduces the LOS gradient, relieves obstructive symptoms and improves oesophageal emptying. The LOS relaxation is improved. Complete coverage of the myotomysed zone by the fundus prevents diverticular formation. Oesophageal mucosal damage from reflux is significant despite the partial fundoplication.     

Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective,matched cohort study

We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p = .03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p = .57) or SAB (0.0% vs 11.7%, p = .13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [7.1, 88.0]; p = .001), MIP-1β (30.7 pg/ml [30.7, 30.7] vs 243.3 pg/ml [30.7, 344.4]; p = .001), IL-8 (32.0 pg/ml [5.6, 53.1] vs 59.1 pg/ml [39.2, 119.4]; p = .003), IL-15 (12.0 pg/ml [12.0, 12.0] vs 12.0 pg/ml [12.0, 126.7]; p = .03), and IFN-α (5.1 pg/mL [5.1, 5.1] vs 5.1 pg/ml [5.1, 26.3]; p = .04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2 pg/ml [194.6] vs 656.5 pg/ml [147.6]; p = .046).     

The association between stressful life events and respiratory infections during the first 4 years of life: The Environmental Determinants of Diabetes in the Young study

The aim of this study was to conduct a prospective analysis of the association between negative life events (NLEs) and respiratory infections in children genetically at risk for islet autoimmunity (IA) and type 1 diabetes (T1D). Long‐ and short‐term temporal associations between NLEs and rate of respiratory infection episodes (RIEs) in 5,618 children in The Environmental Determinants of Diabetes in the Young study for at least 1 up to 4 years were analysed. All models were adjusted for demographic, day care, season of infection, and psychosocial factors associated with the rate of child RIEs between study visits. The rate of child RIEs was 26% higher in Europe (Sweden, Finland, Germany) than in the United States (rate ratio [RR] = 1.26, p < 0.001). However, the percentage of child NLEs (odds ratio [OR] = 1.18, p < 0.001) and mother NLEs (OR = 1.83, p < 0.001) was higher in the United States compared with Europe. In both continents (Europe, RR = 1.12, p < 0.001; United States, RR = 1.07, p = 0.006), high child cumulative NLEs (>1 NLE per year since study inception) was significantly associated with an increased rate of child RIEs. This large‐scale prospective study confirms observations that stress may increase the susceptibility for infections in paediatric populations and suggests at least one mechanism by which stress could increase risk for IA and T1D in genetically at risk children.     

Prognostic factors and long-term results of pulmonary metastasectomy for pediatric histologies

Objective: Pulmonary resection in metastatic pediatric solid tumors is an accepted method of treatment. The purpose of this study was to determine the clinical course, outcome and prognostic factors after surgery. Methods: A retrospective analysis from 1985 to 2006 of 52 patients less than 17 years old at the time of tumor diagnosis and submitted to thoracotomy for pulmonary metastatic disease was performed. Three had nodules excised which proved to be benign at histology and were excluded from further analysis. There were 28 males and 21 females with median age of 13.2 years [2–36] at the time of metastasectomy. The primaries were osteosarcoma (25), Ewing’s sarcoma (6), Wilms’ tumors (4), hepatoblastoma (3) and miscellaneous (11). Pulmonary metastases were encountered either at the time of initial diagnosis (18%) or occurring within 1 month to 22 years. Disease free interval (DFI) was equal or less than 2 years in 31 (63%) patients and more than 2 years in 18 (37%). Results: Patients had one (24), two (16), three (2), four or more (7) metastasectomies resulting in a total of 95 thoracotomies. Wedges (75%) were performed more frequently than anatomic resections (25%). The number of resected metastatic nodules ranged from 1 to 45, median 3. There were no perioperative deaths. There were six complications: pneumothoraces requiring chest tube drainage in two cases. Resection was incomplete in four cases. The mean drainage time and hospital length of stay were 2.7 and 5 days, respectively. Using the date of pulmonary resection as the starting point, 5-year survival rate was 25%. By univariate analysis, we found that a significantly longer survival was observed for patients with a complete resection (p = 0.004), with two or less metastases (p = 0.0004), with unilateral metastases (p = 0.001) or when the DFI was more than 2 years (p = 0.003). By multivariate analysis, we showed that the number of pulmonary metastases was an independent predictor of survival. Conclusion: We conclude that resection of pulmonary metastases of pediatric solid tumors is a safe and effective treatment that offers improved survival benefit in carefully selected patients within a multidisciplinary approach for pediatric cancer. Prognosis related criteria that support patient selection for surgery are identified.     

Bone Microarchitecture and Strength in Long-Standing Type 1 Diabetes

Type 1 diabetes (T1DM) is associated with an increased fracture risk, specifically at nonvertebral sites. The influence of glycemic control and microvascular disease on skeletal health in long-standing T1DM remains largely unknown. We aimed to assess areal (aBMD) and volumetric bone mineral density (vBMD), bone microarchitecture, bone turnover, and estimated bone strength in patients with long-standing T1DM, defined as disease duration ≥25 years. We recruited 59 patients with T1DM (disease duration 37.7 ± 9.0 years; age 59.9 ± 9.9 years.; body mass index [BMI] 25.5 ± 3.7 kg/m²; 5-year median glycated hemoglobin [HbA1c] 7.1% [IQR 6.82–7.40]) and 77 nondiabetic controls. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT) at the ultradistal radius and tibia, and biochemical markers of bone turnover were assessed. Group comparisons were performed after adjustment for age, gender, and BMI. Patients with T1DM had lower aBMD at the hip (p < 0.001), distal radius (p = 0.01), lumbar spine (p = 0.04), and femoral neck (p = 0.05) as compared to controls. Cross-linked C-telopeptide (CTX), a marker of bone resorption, was significantly lower in T1DM (p = 0.005). At the distal radius there were no significant differences in vBMD and bone microarchitecture between both groups. In contrast, patients with T1DM had lower cortical thickness (estimate [95% confidence interval]: −0.14 [−0.24, −0.05], p < 0.01) and lower cortical vBMD (−28.66 [−54.38, −2.93], p = 0.03) at the ultradistal tibia. Bone strength and bone stiffness at the tibia, determined by homogenized finite element modeling, were significantly reduced in T1DM compared to controls. Both the altered cortical microarchitecture and decreased bone strength and stiffness were dependent on the presence of diabetic peripheral neuropathy. In addition to a reduced aBMD and decreased bone resorption, long-standing, well-controlled T1DM is associated with a cortical bone deficit at the ultradistal tibia with reduced bone strength and stiffness. Diabetic neuropathy was found to be a determinant of cortical bone structure and bone strength at the tibia, potentially contributing to the increased nonvertebral fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Assessment of aortic annulus dimensions for Edwards SAPIEN Transapical Heart Valve implantation by computed tomography: calculating average diameter using a virtual ring method

Objective: Accurate preoperative assessment of the aortic annulus dimensions is critical in patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS. Using multislice computed tomography (MSCT), we evaluated a novel approach to quantify aortic annulus dimensions using cross-sectional area (CSA) assessment and average diameter calculation compared with the commonly applied electronic caliper measurements in patients undergoing transapical implantation of the Edwards SAPIEN Transcatheter Heart Valve. Methods: Seventy-one patients underwent pre-TAVI MSCT with the following dimensions assessed at the level of the most basal attachment points of all three aortic cusps joined by a virtual ring: CSA, calculated average annulus diameter (CAAD), and minimal, maximum, sagittal and coronal diameters. Measurements were compared with post-TAVI MSCT data sets at the level of the ventricular stent ending in 24 patients. Pre-TAVI measurements were compared to those taken post-TAVI. Eligibility to balloon-expandable TAVI was evaluated based on the different measurements. Results: The Edwards SAPIEN valve (23 mm, n = 8; 26 mm, n = 16) was implanted 2.1 ± 1.1 mm below the non-coronary sinus. Pre-TAVI CAAD was 23.0 ± 1.6 mm; post-TAVI CAAD was 23.0 ± 1.1 mm. Post-TAVI CSA was circular in 18 patients (75%) and ovoid in six (25%). Pre- and post-TAVI assessment showed strong correlation for CSA and CAAD (r = 0.835, p < 0.001; r = 0.841, p < 0.001, respectively). Minimal, maximum, coronal and sagittal dimension correlated weakly between pre- and post-TAVI measurements (r = 0.435–0.632, p = 0.001–0.034). Conclusion: Pre-TAVI CSA assessment and average diameter calculation using a virtual ring method is able to predict the post-interventional configuration of the annulus after balloon-expandable TAVI. We regard this approach as the best-available method to select the appropriate prosthesis size for balloon-expandable TAVI. Specific MSCT-based sizing recommendations should be developed.     

The Effects of Type 1 Diabetes and Diabetic Peripheral Neuropathy on the Musculoskeletal System: A Case–Control Study

Fracture risk is increased in type 1 diabetes (T1D). Diabetic neuropathy might contribute to this increased risk directly through effects on bone turnover and indirectly through effects on balance, muscle strength, and gait. We compared patients with T1D with (T1DN+, n = 20) and without (T1DN−, n = 20) distal symmetric sensorimotor polyneuropathy and controls (n = 20). We assessed areal bone mineral density (aBMD) and appendicular muscle mass by dual-energy X-ray absorptiometry, microarchitecture by high-resolution peripheral quantitative tomography at the standard ultra-distal site and at an exploratory 14% bone length site at the tibia and radius, bone turnover markers, and muscle strength, gait, and balance by Short Physical Performance Battery (SPPB). At the standard ultra-distal site, tibial cortical porosity was 56% higher in T1DN+ compared with T1DN− (p = .009) and correlated positively with the severity of neuropathy (Toronto Clinical Neuropathy Score; r = 0.347, p = .028) and negatively with nerve conduction amplitude and velocity (r = −0.386, p = .015 and r = −0.358, p = .025, respectively). Similar negative correlations were also observed at the radius (r = −0.484, p = .006 and r = −0.446, p = .012, respectively). At the exploratory 14% offset site (less distal), we found higher trabecular volumetric BMD (tibia 25%, p = .024; radius 46%, p = .017), trabecular bone volume (tibia 25%, p = .023; radius 46%, p = .017), and trabecular number (tibia 22%, p = .014; radius 30%, p = .010) in T1DN– compared with controls. Both CTX and PINP were lower in participants with TD1 compared with controls. No difference was found in aBMD and appendicular muscle mass. T1DN+ had worse performance in the SPPB compared with T1DN– and control. In summary, neuropathy was associated with cortical porosity and worse performance in physical tests. Our findings suggest that bone structure does not fully explain the rate of fractures in T1D. We conclude that the increase in the risk of fractures in T1D is multifactorial with both skeletal and non-skeletal contributions. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).