Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.

Optimal EPO dosing in hemodialysis patients using a non-linear model predictive control approach.

Anemia management with erythropoiesis stimulating agents is a challenging task in hemodialysis patients since their response to treatment varies highly. In general, it is difficult to achieve and maintain the predefined hemoglobin (Hgb) target levels in clinical practice. The aim of this study is to develop a fully personalizable controller scheme to stabilize Hgb levels within a narrow target window while keeping drug doses low to mitigate side effects. First in-silico results of this framework are presented in this paper. Based on a model of erythropoiesis we formulate a non-linear model predictive control (NMPC) algorithm for the individualized optimization of epoetin alfa (EPO) doses. Previous to this work, model parameters were estimated for individual patients using clinical data. The optimal control problem is formulated for a continuous drug administration. This is currently a hypothetical form of drug administration for EPO as it would require a programmable EPO pump similar to insulin pumps used to treat patients with diabetes mellitus. In each step of the NMPC method the open-loop problem is solved with a projected quasi-Newton method. The controller is successfully tested in-silico on several patient parameter sets. An appropriate control is feasible in the tested patients under the assumption that the controlled quantity is measured regularly and that continuous EPO administration is adjusted on a daily, weekly or monthly basis. Further, the controller satisfactorily handles the following challenging problems in simulations: bleedings, missed administrations and dosing errors.

Designing combination therapies with modeling chaperoned machine learning.

Chemotherapy resistance is a major challenge to the effective treatment of cancer. Thus, a systematic pipeline for the efficient identification of effective combination treatments could bring huge biomedical benefit. In order to facilitate rational design of combination therapies, we developed a comprehensive computational model that incorporates the available biological knowledge and relevant experimental data on the life-and-death response of individual cancer cells to cisplatin or cisplatin combined with the TNF-related apoptosis-inducing ligand (TRAIL). The model's predictions, that a combination treatment of cisplatin and TRAIL would enhance cancer cell death and exhibit a "two-wave killing" temporal pattern, was validated by measuring the dynamics of p53 accumulation, cell fate, and cell death in single cells. The validated model was then subjected to a systematic analysis with an ensemble of diverse machine learning methods. Though each method is characterized by a different algorithm, they collectively identified several molecular players that can sensitize tumor cells to cisplatin-induced apoptosis (sensitizers). The identified sensitizers are consistent with previous experimental observations. Overall, we have illustrated that machine learning analysis of an experimentally validated mechanistic model can convert our available knowledge into the identity of biologically meaningful sensitizers. This knowledge can then be leveraged to design treatment strategies that could improve the efficacy of chemotherapy.

Computer-Assisted Propofol Sedation for Esophagogastroduodenoscopy Is Effective, Efficient, and Safe.

BACKGROUND AND AIMS: Computer-assisted propofol sedation (CAPS) allows non-anesthesiologists to administer propofol for gastrointestinal procedures in relatively healthy patients. As the first US medical center to adopt CAPS technology for routine clinical use, we report our 1-year experience with CAPS for esophagogastroduodenoscopy (EGD). METHODS: Between September 2014 and August 2015, 926 outpatients underwent elective EGDs with CAPS at our center. All EGDs were performed by 1 of 17 gastroenterologists certified in the use of CAPS. Procedural success rates, procedure times, and recovery times were compared against corresponding historical controls done with midazolam and fentanyl sedation from September 2013 to August 2014. Adverse events in CAPS patients were recorded. RESULTS: The mean age of the CAPS cohort was 56.7 years (45% male); 16.2% of the EGDs were for variceal screening or Barrett's surveillance and 83.8% for symptoms. The procedural success rates were similar to that of historical controls (99.0% vs. 99.3%; p = 0.532); procedure times were also similar (6.6 vs. 7.4 min; p = 0.280), but recovery time was markedly shorter (31.7 vs. 52.4 min; p < 0.001). There were 11 (1.2%) cases of mild transient oxygen desaturation (< 90%), 15 (1.6%) cases of marked agitation due to undersedation, and 1 case of asymptomatic hypotension. In addition, there were six (0.6%) patients with more pronounced desaturation episodes that required brief (< 1 min) mask ventilation. There were no other serious adverse events. CONCLUSIONS: CAPS appears to be a safe, effective, and efficient means of providing sedation for EGD in healthy patients. Recovery times were much shorter than historical controls.

On medical application of neural networks trained with various types of data.

Neural networks have garnered attention over the past few years. A neural network is a typical model of machine learning that is used to identify visual patterns. Neural networks are used to solve a wide variety of problems, including image recognition problems and time series prediction problems. In addition, neural networks have been applied to medicine over the past few years. This paper classifies the ways in which neural networks have been applied to medicine based on the type of data used to train those networks. Applications of neural networks to medicine can be categorized two types: automated diagnosis and physician aids. Considering the number of patients per physician, neural networks could be used to diagnose diseases related to the vascular system, heart, brain, spinal column, head, neck, and tumors/cancer in three fields: vascular and interventional radiology, interventional cardiology, and neuroradiology. Lastly, this paper also considers areas of medicine where neural networks can be effectively applied in the future.

Computerized hybrid decision-making system for hormone replacement therapy in menopausal women.

BACKGROUND: The diversity of the results of different hormone replacement therapy (HRT) protocols and the fuzziness of the conclusions have caused problems in routine clinical practice. OBJECTIVE: To develop an intelligent decision-making system for HRT specifically is appropriate as we use the abbrevation HRT in the background section in menopausal women in order to assist physicians. METHODS: This study consisted of 179 peri- and post-menopausal patients who were admitted to Hacettepe University Hospital (between 1996 and 2001) with various menopausal complaints. Database variables used in this study were age, height, weight, menopause duration, clinical condition, HRT duration, and the laboratory test results. Our newly developed multiple-centered fuzzy clustering (MCFC) algorithm was applied to the medical data set to differentiate patient groups. Finally, a hybrid intelligent decision-making system was developed by combining knowledge-based algorithms and the MCFC algorithm results. RESULTS: We have used Fuzzy C-means, K-means, Hard C-means, similarity based clustering, and MCFC algorithms on the medical data set and have determined that the MCFC algorithm is the most appropriate algorithm for our medical model. We have defined 5 clusters and 16 cluster centers. A diagnostic phrase was assigned to each cluster center by the physician and these clusters together with knowledge-based algorithms were used for the decision-making system. CONCLUSIONS: We have developed a computerized hybrid decision-making system recommending HRT to peri- and post-menopausal women in order to assist and protect physicians.

Polimedication: applicability of a computer tool to reduce polypharmacy in nursing homes.

ABSTRACTBackground:The risks of polypharmacy can be far greater than the benefits, especially in the elderly. Comorbidity makes polypharmacy very prevalent in this population; thus, increasing the occurrence of adverse effects. To solve this problem, the most common strategy is to use lists of potentially inappropriate medications. However, this strategy is time consuming. METHODS: In order to minimize the expenditure of time, our group devised a pilot computer tool (Polimedication) that automatically processes lists of medication providing the corresponding Screening Tool of Older Persons' potentially inappropriate Prescriptions alerts and facilitating standardized reports. The drug lists for 115 residents in Santa Marta Nursing Home (Fundación San Rosendo, Ourense, Spain) were processed. RESULTS: The program detected 10.04 alerts/patient, of which 74.29% were not repeated. After reviewing these alerts, 12.12% of the total (1.30 alerts/patient) were considered relevant. The largest number of alerts (41.48%) involved neuroleptic drugs. Finally, the patient's family physician or psychiatrist accepted the alert and made medication changes in 62.86% of the relevant alerts. The largest number of changes (38.64%) also involved neuroleptic drugs. The mean time spent in the generation and review of the warnings was 6.26 minute/patient. Total changes represented a saving of 32.77 € per resident/year in medication. CONCLUSIONS: The application of Polimedication tool detected a high proportion of potentially inappropriate prescriptions in institutionalized elderly patients. The use of the computerized tool achieved significant savings in pharmaceutical expenditure, as well as a reduction in the time taken for medication review.

A Robust Optimization Approach to Cancer Treatment under Toxicity Uncertainty.

The design of optimal protocols plays an important role in cancer treatment. However, in clinical applications, the outcomes under the optimal protocols are sensitive to variations of parameter settings such as drug effects and the attributes of age, weight, and health conditions in human subjects. One approach to overcoming this challenge is to formulate the problem of finding an optimal treatment protocol as a robust optimization problem (ROP) that takes parameter uncertainty into account. In this chapter, we describe a method to model toxicity uncertainty. We then apply a mixed integer ROP to derive the optimal protocols that minimize the cumulative tumor size. While our method may be applied to other cancers, in this work we focus on the treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI). For simplicity, we focus on one particular mode of toxicity arising from TKI therapy, low blood cell counts, in particular low absolute neutrophil count (ANC). We develop optimization methods for locating optimal treatment protocols assuming that the rate of decrease of ANC varies within a given interval. We further investigated the relationship between parameter uncertainty and optimal protocols. Our results suggest that the dosing schedule can significantly reduce tumor size without recurrence in 360 weeks while insuring that toxicity constraints are satisfied for all realizations of uncertain parameters.

Assessment of singlet oxygen dosimetry concepts in photodynamic therapy through computational modeling.

BACKGROUND: In photodynamic therapy (PDT) oxygen plays a vital role in killing tumor cells. Therefore oxygen dosimetry is being thoroughly studied. METHODS: Light distribution into tissue is modelled for radiation-induced fibrosarcoma (RIF) and nodular basal cell carcinoma (nBCC), in order to study the influence of blood flow on singlet oxygen concentration effectively leading to cell death ([1O2]rx) from PDT, within this light distribution. This is achieved through initial oxygen supply rate (g0) and initial molecular oxygen concentration ([3O2]0) calculations. Monte Carlo simulations and mathematical models are used for spatial and temporal distributions of [1O2]rx. Hypoxia conditions are simulated by minimizing [3O2]0 and g0. Furthermore, an optimization algorithm is developed to calculate minimum initial molecular oxygen concentration needed ([3O2]0,min) for constant [1O2]rx, when blood flow changes. RESULTS: Our results validate that in initially well-oxygenated scenarios with normal blood flow maximum [1O2]rx values are significantly higher than corresponding values of hypoxic scenarios both for RIF and nBCC models, with maximum oxygen supply rate percentage variations being independent from g0. Moreover, [1O2]rx appears to be more affected by an increase of g0 than of [3O2]0 values. For low blood flow there is a linear relationship between [3O2]0,min and g0, while for better oxygenated areas high blood flow reduces [3O2]0,min needed in exponential manner. CONCLUSIONS: Blood flow appears to be able to compensate for oxygen consumption. The developed optimization protocol on oxygen dosimetry offers a suitable combination of [3O2]0,min and g0 to achieve constant [1O2]rx, despite possible blood flow variations.

Dacryoendoscopy-guided transcanalicular intralesional interferon alpha 2b for canalicular squamous papillomas.

Canalicular papillomatosis is a rare disorder characterized by a mass lesion arising from the epithelium as a stalk from one of the canalicular walls. Traditionally, they have been treated with an open canaliculotomy and excision biopsy with or without additional cryotherapy. A patient with upper canalicular squamous papillomas treated with dacryoendoscopy-guided transcanalicular intralesional and topical interferon alpha 2b is presented, and the ineffectiveness of interferons in this case is discussed.

USE OF FEMORAL ARTERY ULTRASOUND DURING INTRAARTERIAL CHEMOTHERAPY FOR CHILDREN UNDER 10 KG WITH RETINOBLASTOMA.

PURPOSE: To demonstrate the safety and efficacy of intraarterial chemotherapy (IAC) in small infants (<10 kg) with retinoblastoma. METHODS: Retrospective, consecutive, observational case series of patients treated with IAC. Femoral arterial access was obtained using a micropuncture kit and ultrasound guidance, which enabled direct visualization. Melphalan (1.5-5.0 mg), topotecan (0.3-2.0 mg), and/or carboplatin (30-40 mg) were used. Patients underwent adjuvant therapies including laser, cryotherapy, and intravitreal melphalan if persistent disease or recurrence was observed. RESULTS: Fifty-nine injections were administered to 11 eyes of 6 patients. All eyes but one were classified as International Classification Groups C or D. Median patient weight at first IAC cycle was 9.2 kg (mean, 8.9 kg). Median diameter of the femoral artery at the catheterization site was 3.74 mm, measured by two independent observers. Median follow-up was 21.4 months (range 13.1-34.5 months). All eyes were salvaged. CONCLUSION: This study confirmed the safety and efficacy of IAC in infants under 10 kg. Ultrasound guidance enabled successful catheterization of femoral arteries as small as 2.7 mm in diameter. Patients in this study appeared to require fewer injections and lower total doses of chemotherapy compared with previously reported series of comparably advanced disease in larger infants.

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study.

BACKGROUND: Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. METHODS: This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the "appropriate anaesthesia zone" defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45-60 and systolic arterial pressure of 80-140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. RESULTS: Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0-40) vs 5 (0-116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2-20) vs 8 (2-60) days, P=0.017). CONCLUSIONS: SmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: NCT 02556658.

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

One year experience with computer-assisted propofol sedation for colonoscopy.

AIM: To report our one-year experience with computer assisted propofol sedation (CAPS) for colonoscopy as the first United States Medical Center to adopt CAPS technology for routine clinical use. METHODS: Between September 2014 and August 2015, 2677 patients underwent elective outpatient colonoscopy with CAPS at our center. All colonoscopies were performed by 1 of 17 gastroenterologists certified in the use of the CAPS system, with the assistance of a specially trained nurse. Procedural success rates, polyp detection rates, procedure times and recovery times were recorded and compared against corresponding historical measures from 2286 colonoscopies done with midazolam and fentanyl from September 2013 to August 2014. Adverse events in the CAPS group were recorded. RESULTS: The mean age of the CAPS cohort was 59.9 years (48.7% male); 31.3% were ASA I, 67.3% ASA II and 1.4% ASA III. 45.1% of the colonoscopies were for screening, 31.5% for surveillance, and 23.4% for symptoms. The mean propofol dose administered was 250.7 mg (range 16-1470 mg), with a mean fentanyl dose of 34.1 mcg (0-100 mcg). The colonoscopy completion and polyp detection rates were similar to that of historical measures. Recovery times were markedly shorter (31 min vs 45.6 min, P < 0.001). In CAPS patients, there were 20 (0.7%) cases of mild desaturation (< 90%) treated with a chin lift and reduction or temporary discontinuation of the propofol infusion, 21 (0.8%) cases of asymptomatic hypotension (< 90 systolic blood pressure) treated with a reduction in the propofol rate, 4 (0.1%) cases of marked agitation or discomfort due to undersedation, and 2 cases of pronounced transient desaturation requiring brief (< 1 min) mask ventilation. There were no sedation-related serious adverse events such as emergent intubation, unanticipated hospitalization or permanent injury. CONCLUSION: CAPS appears to be a safe, effective and efficient means of providing moderate sedation for colonoscopy in relatively healthy patients. Recovery times were much shorter than historical measures. There were few adverse events, and no serious adverse events, related to CAPS.

Computational fluid dynamics study of intra-arterial chemotherapy for oral cancer.

BACKGROUND: Intra-arterial chemotherapy (IAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, distribution of anticancer agent into several branches of the external carotid artery (ECA) in IAC has not demonstrated sufficient treatment efficacy. To improve the effectiveness of IAC, the flow distribution of anticancer agent into the branches of the ECA in several IAC methods was investigated using computational fluid dynamics (CFD). METHODS: Patient-specific three-dimensional vessel models were created from CT images of 2 patients with tongue cancer. Catheter models were combined with the vessel models. Thirty-two models were generated with varying vertical and horizontal positions of the catheter tip. With the use of a zero-dimensional resistance model of the peripheral vessel network, conventional IAC and superselective IAC were simulated in 30 and 2 models, respectively. The flow distribution of anticancer agent into the branches of the ECA was investigated in 32 models. Additionally, the blood streamline was traced from the inlet of the common carotid artery toward each outlet to examine the flow of anticancer agent in all models, and the wall shear stress of the vessel was calculated for some models. RESULTS: The CFD simulations could be conducted within a reasonable computational time. In several models, the anticancer agent flowed into the target artery only when the catheter tip was located below the bifurcation of the ECA and each target artery. Furthermore, the anticancer agent tended to flow into the target artery when the catheter tip was shifted toward the target artery. In all ECA branches that had flow of anticancer agent, the blood streamlines to the target arteries contacted the catheter tip. Anticancer agent flowed into only the target artery in patients' models for superselective IAC. However, high wall shear stress was observed at the target artery in one patient's model. CONCLUSIONS: This CFD study showed that location of the catheter tip was important in controlling the anticancer agent in conventional IAC. The distribution rate of anticancer agent into the tumor-feeding artery tended to increase when the catheter tip was placed below and toward the target artery. Although superselective IAC can reliably supply anticancer agent to the target artery, high wall shear stress at the target artery can occur, depending on vessel geometry of the patient, which may cause serious complications during the treatment.

Optimal strategy in chemotherapy for Malthusian model of cancer growth.

PURPOSE: The problem of optimal strategy in cancer chemotherapy is reconsidered. Two incompatible goals should be completed: the number of cancer cells in the patient's body should be reduced and the toxic effect of the therapy should be minimized. Such problem may be formulated in optimal control. The control function is the amount of the drug administered in the time unit. METHODS: The Malthusian model of cell population growth is employed where the rate of increase of the number of cancer cells is proportional to the number of cells in population and an intrinsic rate that usually is assumed to be constant. The performance index is the amount of the drug cumulated in the patient's body and it is minimized. A non-standard method of optimal control is used - method of Miele. RESULTS: The optimal solutions are obtained for three cases: constant intrinsic rate, monotonically increasing/decreasing intrinsic rate and for periodic intrinsic rate. The optimal control is ununique for the first case - the result is irrespective of the strategy. Such result has been known earlier. The optimal control is unique for other cases and it is of bang-bang type. CONCLUSIONS: The ununique solution for constant intrinsic rate is surprising, therefore a mechanical analogy is given. The optimal strategy is in accordance with clinical experience for decreasing intrinsic rate. The optimal control is a periodic function of time for the intrinsic rate of sin/cos type - the drug should be administered, as its value is relatively high.

The First US Clinical Experience With Computer-Assisted Propofol Sedation: A Retrospective Observational Comparative Study on Efficacy, Safety, Efficiency, and Endoscopist and Patient Satisfaction.

BACKGROUND: Computer-assisted propofol sedation (CAPS) is now approved for moderate sedation of American Society of Anesthesiologists (ASA) class I and II patients undergoing routine endoscopy. As the first US medical center to adopt CAPS for routine clinical use, we compared patient and endoscopist satisfaction with CAPS versus midazolam and fentanyl (MF) sedation. METHODS: Patients who underwent elective outpatient upper endoscopy and colonoscopy with CAPS were compared with concurrent patients sedated with MF. The primary end points were patient satisfaction (measured by the validated Patient Sedation Satisfaction Index [PSSI]), and endoscopist satisfaction (Clinician Sedation Satisfaction Index [CSSI]). Secondary end points included procedural success rates, polyp detection rates, adverse events, and procedure/recovery times. Multivariable regression was used for comparative analysis. RESULTS: CAPS was utilized to sedate 244 patients, of whom 55 underwent upper endoscopy, 173 colonoscopy, and 16 double procedures. During the same period, 75 upper endoscopies, 223 colonoscopies, and 30 doubles were performed with MF on similar patients. For upper endoscopy, the procedural success rate was 98.2% for CAPS versus 98.7% for MF (P = .96), whereas for colonoscopy, the success rate was 98.9% vs 98.8% (P = .59). Colonoscopic polyp detection rate was 54.5% for CAPS and 59.3% for MF (P = .67). Procedure times were similar between CAPS and MF. For CAPS, the mean recovery time was 26.4 vs 39.1 minutes for MF (P < .001). One CAPS patient required mask ventilation, 4 experienced asymptomatic hypotension or desaturation, and 5 experienced marked agitation resulting from undersedation. For MF, 5 patients had hypotension or desaturation, and 8 experienced undersedation. For colonoscopy, the CAPS group had higher PSSI scores for sedation adequacy, the recovery process and global satisfaction, and higher CSSI scores for ease of sedation administration, the recovery process and global satisfaction. For upper endoscopy and doubles, the CAPS CSSI score was higher for the recovery process only. All P values were adjusted for confounding by using regression analysis. CONCLUSIONS: In low-risk patients, CAPS appears to be effective and efficient. CAPS is associated with higher satisfaction than MF for colonoscopies and, to a lesser extent, upper endoscopies.

Realtime Tracking of the Photobleaching Trajectory During Photodynamic Therapy.

OBJECTIVE: Photodynamic therapy (PDT) is an alternative treatment for cancer, which involves the administration of a photosensitizing agent that is activated by light at a specific wavelength. This illumination causes after a sequence of photoreactions, the production of reactive oxygen species responsible for the death of the tumor cells but also the degradation of the photosensitizing agent, which then loose the fluorescence properties. The phenomenon is commonly known as the photobleaching process and can be considered as a therapy efficiency indicator. METHODS: This paper presents the design and validation of a real-time controller able to track a preset photobleaching trajectory by modulating the light impulses width during the treatment sessions. RESULTS: This innovative solution was validated by in vivo experiments that have shown a significantly improvement of reproducibility of the interindividual photobleaching kinetic. CONCLUSION: We believe that this approach could lead to personalized PDT modalities. SIGNIFICANCE: This work may open new perspectives in the control and optimization of photodynamic treatments.

CLINICAL ASPECTS OF GLYCEMIC MONITORING AND CONTOL IN PATIENTS IN THE EARLY POSTOPERATIVE PERIOD.

INTRODUCTION: At present, no doubt enhanced by the attention of clinicians to monitor blood glucose and methods of its correction in ICU patients. Evidence of the effect of the expressed glycemic balance disorders on the results of treatment of such patients determine of the problem. Attempts to create a computer algorithm to determine the rate of insulin. The aim of the study was to investigate the efficacy and safety of the module Space glycemic control (SGC, "BBraun Germany) with intravenous insulin therapy in patients with thoracoabdominal surgery. MATERIAL AND METHODS: Single-center prospective observational study was conducted in the ICU in 50 patients in the early period after operations on the abdominal and thoracic cavity, mediastinum. RESULTS: The average duration of the monitoring group with SGC was 57 hours (17 to 280 hours). The average length of the period during which the patients were recorded in the target range glycemia was 80.4% of the total time of SGC monitoring. The average value of glucose in capillary blood proved to 7,6?1,58 mmol/l. The incidence of severe hypoglycemia was 2% (1 patient). CONCLUSION: Application module SGC should expedient be used in patients after extensive thoracoabdiminal surgical procedures in which recorded postoperative hyperglycemia.

USE OF A COMPUTER-GUIDED GLUCOSE MANAGEMENT SYSTEM TO IMPROVE GLYCEMIC CONTROL AND ADDRESS NATIONAL QUALITY MEASURES: A 7-YEAR, RETROSPECTIVE OBSERVATIONAL STUDY AT A TERTIARY CARE TEACHING HOSPITAL.

OBJECTIVE: Inpatient hyperglycemia, hypoglycemia, and glucose variability are associated with increased mortality. The use of an electronic glucose management system (eGMS) to guide intravenous (IV) insulin infusion has been found to significantly improve blood glucose (BG) control. This retrospective observational study evaluated the 7-year (January 2009-December 2015) impact of the EndoTool® eGMS in intensive and intermediate units at Vidant Medical Center, a 900-bed tertiary teaching hospital. METHODS: Patients assigned to eGMS had indications for IV insulin infusion, including uncontrolled diabetes, stress hyperglycemia, and/or postoperative BG levels >140 mg/dL. This study evaluated time required to achieve BG control (<180 mg/dL; <140 mg/dL for cardiovascular surgery patients); hypoglycemia incidence (<70 and <40 mg/dL); glucose variability (assessed by SD and coefficient of variation percentage [CV%]); excursions (BG levels >180 mg/dL after control attained); and the impact of eGMS on hospital-acquired condition (HAC)-8 rates. RESULTS: Data were available for all treated patients (492,078 BG readings from 16,850 patients). With eGMS, BG levels were brought to target within 1.5 to 2.3 hours (4.5 to 4.8 hours for cardiovascular patients). Minimal hypoglycemia was observed (BG values <70 mg/dL, 0.93%; <40 mg/dL, 0.03%), and analysis of variance of BG values <70 mg/dL showed significant reductions over time in hypoglycemia frequency, from 1.04% in 2009 to 0.46% in 2015 (P<.0001). The CV% per patient visit was 26.5 (±12.9)%, and 4% of patients experienced glucose excursions (defined as BG levels >180 mg/dL once control was attained). HAC-8 rates were reduced from 0.083 per 1,000 patients (2008) to 0.032 per 1,000 patients (2011). CONCLUSION: The use of eGMS resulted in rapid, effective control of inpatient BG levels, including significantly reduced hypoglycemia rates. ABBREVIATIONS: BG = blood glucose CMS = Centers for Medicare and Medicaid Services CV = coefficient of variation CV% = coefficient of variation percentage eGMS = electronic glucose management system GV = glycemic variability HAC = Hospital-Acquired Condition ICU = intensive care unit IU = intermediate unit IV = intravenous LOS = length of stay VMC = Vidant Medical Center.