Continuous Metabolic Monitoring in Infant Cardiac Surgery: Toward an Individualized Cardiopulmonary Bypass Strategy

Cardiopulmonary bypass (CPB) in infants is associated with morbidity due to systemic inflammatory response syndrome (SIRS). Strategies to mitigate SIRS include management of perfusion temperature, hemodilution, circuit miniaturization, and biocompatibility. Traditionally, perfusion parameters have been based on body weight. However, intraoperative monitoring of systemic and cerebral metabolic parameters suggest that often, nominal CPB flows may be overestimated. The aim of the study was to assess the safety and efficacy of continuous metabolic monitoring to manage CPB in infants during open‐heart repair. Between December 2013 and October 2014, 31 consecutive neonates, infants, and young children undergoing surgery using normothermic CPB were enrolled. There were 18 male and 13 female infants, aged 1.4 ± 1.7 years, with a mean body weight of 7.8 ± 3.8 kg and body surface area of 0.39 m². The study was divided into two phases: (i) safety assessment; the first 20 patients were managed according to conventional CPB flows (150 mL/min/kg), except for a 20‐min test during which CPB was adjusted to the minimum flow to maintain MVO₂ >70% and rSO₂ >45% (group A); (ii) efficacy assessment; the following 11 patients were exclusively managed adjusting flows to maintain MVO2 >70% and rSO2 >45% for the entire duration of CPB (group B). Hemodynamic, metabolic, and clinical variables were compared within and between patient groups. Demographic variables were comparable in the two groups. In group A, the 20‐min test allowed reduction of CPB flows greater than 10%, with no impact on pH, blood gas exchange, and lactate. In group B, metabolic monitoring resulted in no significant variation of endpoint parameters, when compared with group A patients (standard CPB), except for a 10% reduction of nominal flows. There was no mortality and no neurologic morbidity in either group. Morbidity was comparable in the two groups, including: inotropic and/or mechanical circulatory support (8 vs. 1, group A vs. B, P = 0.07), reexploration for bleeding (1 vs. none, P = not significant [NS]), renal failure requiring dialysis (none vs. 1, P = NS), prolonged ventilation (9 vs. 4, P = NS), and sepsis (2 vs. 1, P = NS). The present study shows that normothermic CPB in neonates, infants, and young children can be safely managed exclusively by systemic and cerebral metabolic monitoring. This strategy allows reduction of at least 10% of predicted CPB flows under normothermia and may lay the ground for further tailoring of CPB parameters to individual patient needs.     

<Superscript>11</Superscript>C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series

Purpose

To evaluate ¹¹C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing ¹¹C-choline PET/CT during BCR.

Methods

We retrospectively analysed 9,632 ¹¹C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed.

Results

Overall, 52.8 % of the ¹¹C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 – 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive ¹¹C-choline PET/CT scan (p?<?0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 ¹¹C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans.

Conclusion

In a large cohort of patients, the feasibility of ¹¹C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.

     

Subsyndromal depression: an impact on quality of life?

OBJECTIVE: The objective of this study was to demonstrate the association between quality of life and subsyndromal depression in a primary care clinic in a Brazilian sample. METHODS: This was a cross-sectional study. The cases were divided into three groups according to the severity of depressive symptoms: 1) subjects with major depressive disorder; 2) subjects with subsyndromal depression; 3) subjects without depressive symptoms--controls. The participants completed the World Health Organization Instrument to Assess Quality of Life (WHOQOL-BREF), the Quality of Life--Depression (QLDS), the Centers for Epidemiologic Studies--Depression instrument (CES-D), and the Composite International Diagnostic Interview (CIDI). RESULTS: The sample consisted of 438 primary care users (35.2% of them had subsyndromal depression). The subjects with major depression presented the worst impairment of quality of life, which was measured by the WHOQOL-BREF and the QLDS. The patients with subsyndromal depression had a smaller impact on their quality of life and the subjects without depression presented an even lower impact. The hierarchical linear regression involving demographic variables and the severity of depressive symptoms showed that the severity of depression was the variable with higher correlation with quality of life dimensions, presenting increased variation in the domains (from 9% to 24%). CONCLUSIONS: The results suggest that subsyndromal depression causes impairment of the quality of life in primary care patients of a Brazilian sample.     

Patient education in Parkinson's disease: Formative evaluation of a standardized programme in seven European countries

OBJECTIVE: To evaluate a newly developed education programme for Parkinson's disease (PD) patients. METHODS: The programme consisted of eight sessions and aimed at improving knowledge and skills related to self-monitoring, health promotion, stress management, depression, anxiety, social competence, and social support, all with special reference to PD. The programme was formatively evaluated in seven European countries (Spain, Finland, Italy, The Netherlands, United Kingdom, Estonia, Germany) with 151 patients diagnosed with idiopathic PD. The evaluation included patients' ratings of the comprehensibility and feasibility of the programme as well as mood ratings before and after each session. Patients also completed questionnaires at the beginning and end of the programme to explore possible changes in disease-related psychosocial problems, quality of life, and depression. RESULTS: The programme was feasible to run, and patients were able to understand its elements. Patients reported mood elevations following individual sessions and reduced disease-related psychosocial problems after completing the programme. There were no substantial differences in results between cultures. CONCLUSION: Patient education appears to have potential as a useful and feasible intervention, complementing medical treatment in PD. PRACTICE IMPLICATIONS: The present programme will soon be available in seven European languages and can be tested in different health care systems.     

Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells.     

Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: a three-way crossover study

BACKGROUND: Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. OBJECTIVE: The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. METHODS: Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. RESULTS: The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P<0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P<0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P<0.001) and DBP (-18.6 [4] mm Hg; P<0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P<0.001) and PSTP (36.6%; P<0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P<0.05) and PSTP (10.4%; P<0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. CONCLUSION: In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.     

A retrospective study on oral anticoagulant prophylaxis in 103 Italian patients with hereditary thrombophilia and thrombosis

Summary The clinical records of 103 Italian patients with inherited thrombophilia and thrombosis were reviewed to estimate the incidence of thrombotic recurrences and major bleeding complications according to the different duration of oral anticoagulant prophylaxis (OAP). The incidence of the first thrombotic recurrence was 2.9, 7.4 and 10.8×100 patients/year, respectively, in subjects receiving lifelong OAP, stopping OAP after a mean of 9 months (range 1–30 months) or not receiving OAP. The probability to remain free from thrombotic recurrences in patients undergoing lifelong OAP, as estimated by the Kaplan-Meier method, was significantly higher in comparison with untreated patients (p<0.001), but did not reach the statistical significance in comparison with patients who stopped prophylaxis. The incidence of further thrombotic recurrences was 1.2, 21.1 and 22.3×100 patients/year, respectively, in the three groups defined above. The difference between patients who prolonged indefinitely OAPvs those who stopped or did not receive OAP was statistically significant (p=0.003). Two intracranial bleedings, one of which fatal, were observed in patients undergoing lifelong OAP, whereas no major bleeding complications occurred in the other two groups. Our study supports the recommendations to continue indefinitely OAP in patients with inherited thrombophilia and recurrent thrombosis, but suggests caution in starting lifelong prophylaxis soon after the first thrombotic event in all patients. Members of the Study Group: F. Baudo (Milano); M. Berrettini (Perugia); G. Castaman (Vicenza); N. Ciavarella (Bari); S. Coccheri (Bologna); V. De Stefano (Roma); A. G. Dettori (Parma); N. Erba (Merate); G. Leone (Roma); P. M. Mannucci (Milano); C. Manotti (Parma); M. G. Mazzucconi (Roma); G. Palareti (Bologna); F. Panicucci (Pisa); E. Pogliani (Monza); F. Rodeghiero (Vicenza); A. Tripodi (Milano).