Safe implementation of robotic-assisted minimally invasive direct coronary artery bypass: application of learning curves and cumulative sum analysis

BackgroundLearning curves are inevitably encountered when first implementing an innovative and complex surgical technique. Nevertheless, a cluster of failures or complications should be detected early, but not deter learning, to ensure safe implementation. Here, we aimed to examine the presence and impact of learning curves on outcome after robotic-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB).MethodsA retrospective analysis of the first 300 RA-MIDCAB surgeries between July 2015 and December 2020 was performed. Learning curves were obtained via logarithmic regression for surgical time. Cumulative sum (CUSUM) analysis was performed for (I) major complications including MI, stroke, repeat revascularization, and mortality, and (II) other complications, including prolonged ventilation, pneumonia, pleura puncture, lung herniation, pericarditis, pleuritis, arrhythmia, wound complications, and delirium. Expected and unacceptable rates were set at 12% and 20%, respectively, for major complications, and at 40% and 60% for other complications, based on historical data in conventional coronary artery bypass grafting (CABG).ResultsDemographic characteristics did not differ between terciles, except for more smokers in the first tercile, and less hypercholesterolemia and more complex procedures in the third tercile. The mean surgical time for all operations was 258±81 minutes, ranging from 127 to 821 minutes. A learning curve was only observed in the first tercile. Subgroup analysis revealed that this learning curve was only observed for procedures consisting of single internal mammary artery (SIMA) with 1 or 2 distal anastomoses but not with bilateral internal mammary arteries (BIMA) or more than 2 distal anastomoses. CUSUM analysis showed that the cumulative rate of major and other complications never crossed the lines for unacceptable rates. Rather, the lower 95% confidence boundary was crossed after 50 cases, indicating improvement in safety.ConclusionsThese results suggest that integration of RA-MIDCAB in the surgical landscape can be safely achieved and complication rates can quickly be reduced below those expected in traditional CABG. Collective experience plays a key role in overcoming the learning curve when more complex procedures and cases are introduced.     

Pretargeting of necrotic tumors with biotinylated hypericin using (123)I-labeled avidin: evaluation of a two-step strategy

As an alternative to directly targeting of necrotic tissue using hypericin, we synthesized a conjugate of hypericin to biotin for use in a pretargeting approach. With this conjugate, we explored the possibility of a two-step pretargeting strategy using (123)I-labeled avidin as effector molecule directed against necrotic RIF-1 tumors. Hypericin was conjugated to biotin-ethylenediamine in a straightforward coupling method using n-hydroxysuccinimide and dicyclohexylcarbodiimide. The necrosis avidity of the conjugate was first confirmed in necrotic liver tissue by means of fluorescence microscopy. Using autoradiography imaging and whole body-biodistribution, the accumulation of (123)I-avidin in necrotic tumor tissue was evaluated 24?h after administration and 48?h after pretargeting with hypericin-biotin. Analysis of autoradiography images show a higher accumulation of (123)I-avidin in pretargeted compared to nontargeted tissue. However, absolute accumulation of (123)I-avidin in necrotic tumors was low as shown by biodistribution experiments. Direct injection of hypericin-biotin or biotin-fluorescein did not substantially improve (123)I-avidin accumulation after pretargeting, pointing towards a poor penetration of avidin in necrotic tissue. Our results show the feasibility of a pretargeting technique using a small molecule as targeting agent. However, for a more efficient accumulation of the effector molecule in necrotic tissue, other pretargeting strategies need to be investigated.     

Protein acetylation and aging

Our results suggest the possible benefit of manipulating an intrinsic aging pathway that is independent of nutrition availability, a potential therapeutic route that might be able to bypass shortcomings of calorie restriction.     

A further exploration of the relationships between immune parameters and the HPA-axis activity in depressed patients

In order to investigate the relationship between the immune apparatus and the hypothalamic-pituitary-adrenal (HPA)-axis activity in depressed patients, we measured in vitro lymphocyte responses to the mitogens Phytohaemagglutinin (PHA), Pokeweed (PWM) and Concanavalin A (Con A) and 8 a.m. baseline cortisol values in plasma, free cortisol excretion in 24 h urine (UFC), basal and post-dexamethasone beta-endorphin values. Major depressed patients with melancholia/psychotic features exhibited a significantly lower mitogen-induced blast transformation as compared to minor and simple major depressed patients. The lymphocyte responses to the three mitogens were significantly inversely related to baseline cortisol values and postdexamethasone beta-endorphin values. The proliferative capacity of lymphocytes to stimulation with PHA and PWM was significantly and positively related to UFC excretion. Up to 45% of the variance in the immune-responses to the mitogens was explained by the baseline cortisol, post-dexamethasone beta-endorphin and UFC values.     

The cost of improving nutritional outcomes through food‐assisted maternal and child health and nutrition programmes in Burundi and Guatemala

Evidence on the cost‐effectiveness of multisectoral maternal and child health and nutrition programmes is scarce. We conducted a prospective costing study of two food‐assisted maternal and child health and nutrition programmes targeted to pregnant women and children during the first 1,000 days (pregnancy to 2 years). Each was paired with a cluster‐randomized controlled trial to evaluate impact and compare the optimal quantity and composition of food rations (Guatemala, five treatment arms) and their optimal timing and duration (Burundi, three treatment arms). We calculated the total and per beneficiary cost, conducted cost consequence analyses, and estimated the cost savings from extending the programme for 2 years. In Guatemala, the programme model with the lowest cost per percentage point reduction in stunting provided the full‐size family ration with an individual ration of corn–soy blend or micronutrient powder. Reducing family ration size lowered costs but failed to reduce stunting. In Burundi, providing food assistance for the full 1,000 days led to the lowest cost per percentage point reduction in stunting. Reducing the duration of ration eligibility reduced per beneficiary costs but was less effective. A 2‐year extension could have saved 11% per beneficiary in Guatemala and 18% in Burundi. We found that investments in multisectoral nutrition programmes do not scale linearly. Programmes providing smaller rations or rations for shorter durations, although less expensive per beneficiary, may not provide the necessary dose to improve (biological) outcomes. Lastly, delivering effective programmes for longer periods can generate cost savings by dispersing start‐up costs and lengthening peak operating capacity.     

Salt and hypertension

The salt hypothesis states that salt is a necessary condition for the genesis of essential hypertension; however, it is not a sufficient condition. Other factors—primarily genetics—are necessary for the expression of the disease. The arguments in favor of this still controversial subject originate from pathophysiology, evolution, history, pharmacology, experimental and clinical medicine, and epidemiology. Epidemiologic observations favoring the hypothesis mostly relate to comparisons between populations, and much less to comparisons within populations. The arguments against this hypothesis are related mostly to the well known difficulties of proving a within-population relationship of a relatively homogeneously distributed variable to an age-related variable (blood pressure). Mortality data derived from stomach cancer and stroke, compared within and between populations, provide only circumstantial, but nevertheless important, evidence in favor of the salt hypothesis. The strong, consistent, and independent association between stomach cancer and stroke mortality is best explained by the level of salt intake in the population. The observations made in Belgium over the last years are consistent with the salt hypothesis. A decrease in salt intake at the population level correlated with a marked decrease in stroke and stomach cancer mortality, larger than in any other European country, except Finland.     

Otitis Externa In Man Caused By The Mite Otodectes Cynotis

A case of external otitis in a farmer's wife caused by Otodectes cynotis is described. O. cynotis is a well known parasite in dogs and cats but has never been reported as a breeding parasite in the human ear.