Lean Thinking to manage a national working group on physics aspects of Stereotactic Body Radiation Therapy.

PURPOSE: To report how the adoption of a Lean Thinking mindset in the management of a national working group (WG) on the physics of stereotactic body radiation therapy (SBRT) contributed to achieve SBRT standardization objectives. METHODS: Vision for the WG has been established as fragmentation reduction and process harmonization enhancement in SBRT for Italian centers. Two main research themes of the technical aspects of SBRT emerged as areas with major standardization improvement needs, small field dosimetry and SBRT planning comparisons, to be investigated through multi-institutional studies. The management of the WG leveraged on the Lean concept of fostering self-organization in a non-hierarchical environment. Four progressive involvement levels were defined for each study. No specific "scientific" pre-experience was required to propose and coordinate a project, just requiring a voluntary commitment. People engagement was measured in terms of number of published articles. The standardization goals have been conducted through a simplified "5S" (Sort, Set in Order, Shine, Standardize, and Sustain) methodology, first considering a phase of awareness (the first three "S"), then identifying and implementing standardization actions (the last two "S"). RESULTS: Since the beginning, 157 medical physicists joined the AIFM/SBRT-WG. Twenty-four papers/reviews/letters have been published in the period 2014-2019 on major radiation oncology journals, authored by >100 physicists (>50% working in small hospitals). Six over 12 first authors worked in peripheral/small hospitals, with no prior publication as first author. These studies contributed to the awareness and standardization phases for both small-field dosimetry and planning. In particular, errors in small-field measurements in 8% of centers were detected thanks to a generalized output factor curve in function of the effective field size created by averaging data available from different Linacs. Furthermore, planner's experience in SBRT was correlated with dosimetric parameters in the awareness phase; while sharing median dose volume histograms (DVHs) reduced variability among centers while keeping the same level of plan complexity. Finally, all the dosimetric parameters statistically significant to the planner experience during the awareness phase, were no longer significantly different in the standardization phase. CONCLUSIONS: The experience of our SBRT-WG has shown how a Lean Thinking mindset could foster the SBRT procedure standardization and spread the physics of SBRT knowledge, enhancing personal growth. Our expectation is to inspire other scientific societies that have to deal with fragmented contexts or pursue processes harmonization through Lean principles.

Diagnostic accuracy of anesthesiology evaluation timing: the 'One-Stop Anesthesia' in pediatric day-surgery.

OBJECTIVE: Assessing timing efficacy of anesthetic evaluation in pediatric day-surgery by a diagnostic accuracy study. AIM: Lowering hospital visits in patients with negative medical history. BACKGROUND: Pediatric patients scheduled for day-surgery procedures can be categorized, according to their history, in two groups. One, the largest, includes healthy patients and the other includes those with medical conditions that necessitate further evaluation. MATERIALS AND METHODS: Clinical data are collected by the pediatric surgeons of our department and reviewed by an anesthetist who then selects the timing of anesthesiology evaluation, which will take place in the same day of the procedure (One-Stop Anesthesia), or some days before it, in a dedicated setting (Pre-Admission Clinic). In 2008, 332 children, older than 12 months, screened by that method, underwent surgical procedures in general anesthesia. RESULTS: Our data were examined using Bayesian Statistical Analysis. In the 'One-Stop Anesthesia' group, true positive were 290 (87.4%) and false positive 4 (1.2%). Of the 38 patients assessed by our Pre-Admission Clinic, true negative were 30 (9%) and false negative 8 (2.4%). Sensibility (97.3%), specificity (88.2%), positive predictive value (98.6%), negative predictive value (78.9%), diagnostic accuracy (96.4%), likelihood positive (8.3), and likelihood negative (0.03) were calculated. CONCLUSIONS: Timing the preoperative anesthesiologist's evaluation avoided 88% of hospital visits, usually to the Pre-Admission Clinic, and thus, it was cost effective, reducing direct and indirect costs of healthcare providers.

Hypotensive anesthesia with propofol and remifentanil: protective effect of alpha-tocopherol on renal function.

STUDY OBJECTIVE: To determine the effect of alpha-tocopherol in patients receiving hypotensive anesthesia with propofol-remifentanil. STUDY DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: 66 ASA physical status I and II patients, aged 32 to 56 years, scheduled for nasal polypectomy. INTERVENTIONS: Patients were allocated into two groups, the treatment and the control groups (T group and C group). T group received alpha-tocopherol 300 mg orally 5 to 6 hours before surgery. MEASUREMENTS: Sampling times and measurements were done before hypotension (t0), 45 minutes after starting hypotension (t1), 90 minutes after starting hypotension (t2), 45 minutes after recovery of normotension (t3), and 24 hours after surgery (t4). Renal function was assessed by testing glomerular and tubular functions: glomerular filtration rate, fractional excretion of sodium (FENA); fractional excretion of urea (FEUN); and urinary N-acetyl-1-beta-D-glucosoaminidase (NAG) index (NAGi). MAIN RESULTS: Glomerular filtration rate values remained unchanged in all patient populations. Fractional excretion of sodium was within reference ranges in both groups at times t0, t1, and t2. At time t3, a significant FE(NA) peak was observed. At this time, FENA was significantly higher in C group than T group (P < 0.001). FEUN time course was similar to the FENA trend. At time t4, FENA and FEUN returned to basal values. At time t3, NAGi was also increased without significant intergroup differences (P < 0.01, P < 0.001, and P < 0.01 vs times t0, t1, t2 in C group, respectively; P < 0.01, P < 0.01, and P < 0.001 vs times t0, t1, and t2 in T group, respectively). CONCLUSIONS: In patients without any renal disease, hypotensive anesthesia with propofol and remifentanil results in a transient tubular dysfunction, which appears to be minimized by the preoperative administration of alpha-tocopherol.

[Postoperative metabolic acidosis: use of three different fluid therapy models]. / L'acidosi metabolica postoperatoria: impiego di tre differenti modeli di fluido-terapia.

Intraoperative fluid administration is considered an important factor in the management of metabolic acidosis following surgical procedures. The aim of this study was to compare three types of intraoperative infusional models in order to evaluate their effect on acid-base changes in the immediate postoperative period as calculated by both the Henderson-Hasselbach equation and the Stewart approach. Forty-seven patients undergoing left hemicolectomy were enrolled in the study and assigned randomly to receiving 0.9% saline alone (Group A, n=16), lactated Ringer's solution alone (Group B, n=16) or 0.9% saline and Ringer's solution, 1:1 ratio (Group C, n=15). Arterial blood samples were taken before operation (t0) and 30 min after extubation (t1) in order to measure the acid-base balance. The results showed a metabolic acidosis status in Group A patients, whereas Group B exhibited metabolic alkalosis only by means of the Stewart method. No difference was found in Group C between the time points t0 and t1 when using either the Henderson-Hasselbach equation or using the Stewart model. We conclude that saline solution in association with Ringer's solution (1:1 ratio) appears to be the most suitable form of intraoperative fluid management in order to guarantee a stable acid-base balance in selected surgical patients during the immediate postoperative period.

Apoptogenic effect of fentanyl on freshly isolated peripheral blood lymphocytes.

BACKGROUND: Opioids may trigger the apoptotic death of widely ranging cell types, and apoptosis contributes to the immune deficiency of critically ill patients and subjects experiencing surgical trauma. There is evidence that an altered mitochondrial membrane potential constitutes an early and irreversible step in the death-signaling pathway of apoptosis. This study investigated whether fentanyl, a opioid widely used in the management of these patients, may induce apoptosis of T cells by altering their mitochondrial membrane potential. METHODS: Peripheral blood lymphocytes were cultured in the presence of 30 ng fentanyl for 60 (time 1), 90 (time 2), and 120 (time 3) minutes, respectively. The cells then were processed for assessment of mitochondrial membrane potential by means of flow cytometry and confocal scanning microscopy. Furthermore, production of reactive oxygen species, expression of the Fas-Fas L pro-apoptotic pathway, and apoptosis frequency were measured by means of flow cytometry. Control cells were incubated for the same times in the complete culture medium without the drug. RESULTS: Flow cytometry analysis showed a significantly increased rate (p < 0.05) of lymphocytes with disrupted mitochondrial membrane potential after incubation with fentanyl for 90 and 120 minutes, as compared with both control cells and lymphocytes cultured in the presence of fentanyl for 60 minutes. In addition, as early as 60 minutes after exposure to fentanyl, cells displayed a disrupted mitochondrial membrane potential when this was assayed by means of confocal laser scanning. These findings were associated with increased production of reactive oxygen species. The frequency of apoptotic lymphocytes was markedly increased (p < 0.05) after 120 minutes of incubation, as compared with untreated cells and cells exposed to fentanyl for only 60 and 90 minutes. Expression of Fas-FasL was not substantially affected by exposure to fentanyl. CONCLUSIONS: Fentanyl may induce a time-dependent apoptosis of lymphocytes by altering their mitochondrial redox metabolism.

Oxidative stress and mitochondrial glutathione in human lymphocytes exposed to clinically relevant anesthetic drug concentrations.

STUDY OBJECTIVE: To evaluate the potential of compounds commonly used in anesthesia practice to affect the intracellular oxidant-antioxidant homeostasis of peripheral blood lymphocytes at clinically relevant concentrations; and to study the changes in reactive oxygen species production and measure the mitochondrial glutathione content. DESIGN: Prospective, in vitro study. SETTING: Experimental medical research laboratory at a University Hospital. MEASUREMENTS: Lymphocytes were isolated from the peripheral blood of 15 healthy donors and incubated for 12 hours at 37 degrees C with the following drug concentrations: thiopental sodium 20 mmoL/mL, droperidol 130 micromol/mL, propofol 60 mmoL/mL, and succinylcholine 17 mmoL/mL. Reactive oxygen species (ROS) generation was determined by hydroethidine and 2',7'-dichlorofluorescein diacetate methods. Mitochondrial glutathione level was assessed using monobromobimane staining. MEASUREMENTS AND MAIN RESULTS: Thiopental-treated lymphocytes exhibited an overgeneration of ROS, but no change was detected in mitochondrial glutathione quantity. Propofol and droperidol could not induce any perturbative effect on the oxidative state of T cells, whereas succinylcholine was found to markedly affect lymphocyte oxidative state both by impairing glutathione content and promoting exaggerated production of ROS. CONCLUSION: Drugs commonly used in anesthesia practice may significantly alter the oxidative state of peripheral T cells. This mechanism could contribute to the immune suppression that occurs transiently in the early postoperative period.