A strategy based on integer programming for optimal dosing and timing of preventive hypoglycemic treatments in type 1 diabetes management.

BACKGROUND AND OBJECTIVES: One of the major problems related to type 1 diabetes (T1D) management is hypoglycemia, a condition characterized by low blood glucose levels and responsible for reduced quality of life and increased mortality. Fast-acting carbohydrates, also known as hypoglycemic treatments (HT), can counteract this event. In the literature, dosage and timing of HT are usually based on heuristic rules. In the present work, we propose an algorithm for mitigating hypoglycemia by suggesting preventive HT consumption, with dosages and timing determined by solving an optimization problem. METHODS: By leveraging integer programming and linear inequality constraints, the algorithm can bind the amount of suggested carbohydrates to standardized quantities (i.e., those available in "off-the-shelf" HT) and the minimal distance between consecutive suggestions (to reduce the nuisance for patients). RESULTS: The proposed method was tested in silico and compared with competitor algorithms using the UVa/Padova T1D simulator. At the cost of a slight increase of HT consumed per day, the proposed algorithm produces the lowest median and interquartile range of the time spent in hypoglycemia, with a statistically significant improvement over most competitor algorithms. Also, the average number of hypoglycemic events per day is reduced to 0 in median. CONCLUSIONS: Thanks to its positive performances and reduced computational burden, the proposed algorithm could be a candidate tool for integration in a DSS aimed at improving T1D management.

Nonlinear Machine Learning Models for Insulin Bolus Estimation in Type 1 Diabetes Therapy.

Type 1 diabetes (T1D) therapy requires multiple daily insulin injections to compensate the lack of endogenous insulin production due to ß-cells destruction. An empirical standard formula (SF) is commonly used for such a task. Unfortunately, SF does not include information on glucose dynamics, e.g. the glucose rate-of-change (ROC) provided by continuous glucose monitoring (CGM) sensor. Hence, SF can sometimes lead to under/overestimations that can cause critical hypo/hyperglycemic episodes during/after the meal. Recently, to overcome this limitation, we proposed new linear regression models, integrating ROC information and personalized features. Despite the first encouraging results, the nonlinear nature of the problem calls for the application of nonlinear models. In this work, random forest (RF) and gradient boosting tree (GBT), nonlinear machine learning methodologies, were investigated. A dataset of 100 virtual subjects, opportunely divided into training and testing sets, was used. For each individual, a single-meal scenario with different meal conditions (preprandial ROC, BG and meal amounts) was simulated. The assessment was performed both in terms of accuracy in estimating the optimal bolus and glycemic control. Results were compared to the best performing linear model previously developed. The two tree-based models proposed lead to a statistically significant improvement of glycemic control compared to the linear approach, reducing the time spent in hypoglycemia (from 32.49% to 27.57-25.20% for RF and GBT, respectively). These results represent a preliminary step to prove that nonlinear machine learning techniques can improve the estimation of insulin bolus in T1D therapy. Particularly, RF and GBT were shown to outperform the previously linear models proposed.Clinical Relevance- Insulin bolus estimation with nonlinear machine learning techniques reduces the risk of adverse events in T1D therapy.

Small bowel occlusion after trans-abdominal preperitoneal hernia approach caused by barbed suture: case report and review of literature.

BACKGROUND: Groin hernioplasty is the most performed intervention in the adults worldwide. Small bowel occlusion after hernioplasty with anterior approach is an unusual complication because the peritoneum is not opened during this procedure. However during TAPP the closure of the peritoneal flap is mandatory. In literature some cases of small bowel occlusion related to the barbed suture for the closure the peritoneum are reported. METHODS: Here we describe a case of a 64-year old male with small bowel obstruction after TAPP caused by the barbed suture used for peritoneal closure. RESULTS: Intrabdominal use of self-anchoring suture is controversial. Some studies reported good results by using this device, while others from gynecologists describe bowel occlusion and volvulus caused by barbed suture. CONCLUSIONS: Self-anchoring device is innovative and reduces operation time. It is most important to know the correct use of this device to reduce some possible troubles.

Hybrid minimally invasive esophagectomy for cancer: impact on postoperative inflammatory and nutritional status.

The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit.

Liver autotransplantation for the treatment of unresectable hepatic metastasis: an uncommon indication-a case report.

Ex situ ex vivo liver surgery represents a method to expand the surgical indications to treat otherwise unresectable liver tumors. We report the case of a 38-year old woman with hepatic metastasis from a pancreatoblastoma that was judged to be unresectable due to the involvement of the three hepatic veins. To treat the primary tumor, she underwent a pancreaticoduodenectomy, adjuvant chemotherapy, and thermal ablation of a liver metastasis. After appropriate preoperative study and with the permission of the ethics committee, she underwent ex situ ex vivo liver resection. The hepatectomy was performed by removing the whole liver en bloc with the retrohepatic vena cava. The inferior vena cava was reconstructed by interposition of a prosthetic graft. The ex situ ex vivo hepatic resection, a left hepatic lobectomy included the lesion in segments 1-5-7-8. The two hepatic veins were reconstructed using patches of saphenous vein. The organ was preserved continuously for 6 hours using hypothermic perfusion with 4°C Celsior solution. The liver was then reimplanted performing an anastomosis between the reconstructed hepatic veins and the caval prostheses. The patient was discharged at postoperative day 22 and is currently disease-free at 8 months after surgery and 44 months after the initial diagnosis. Ex situ, ex vivo liver surgery offers an additional option for patients with both primary and secondary liver tumors considered to be unresectable using traditional surgical approaches.

Subnormothermic machine perfusion for non-heart-beating donor liver grafts preservation in a Swine model: a new strategy to increase the donor pool?

We previously reported that subnormothermic machine perfusion (sMP; 20°C) is able to improve the preservation of livers obtained from non-heart-beating donors (NHBDs) in rats. We have compared sMP and standard cold storage (CS) to preserve pig livers after 60 minutes of cardiac arrest. In the sMP group livers were perfused for 6 hours with Celsior at 20°C. In the CS group they were stored in Celsior at 4°C for 6 hours as usual. To simulate liver transplantation, both sMP- and CS-preserved livers were reperfused using a mechanical continuous perfusion system with autologus blood for 2 hours at 37°C. At 120 min after reperfusion aspartate aminotransferase levels in sMP versus CS were 499 ± 198 versus 7648 ± 2806 U/L (P < .01); lactate dehydrogenase 1685 ± 418 versus 12998 ± 3039 U/L (P < .01); and lactic acid 4.78 ± 3.02 versus 10.46 ± 1.79 mmol/L (P < .01) respectively. The sMP group showed better histopathologic results with significantly less hepatic damage. This study confirmed that sMP was able to resuscitate liver grafts from large NHBD animals.

Liver transplantation for massive hepatomegaly due to polycystic liver disease: an extreme case.

BACKGROUND: Polycystic liver disease (PLD) is due to a genetic disorder and frequently coexists with polycystic kidney disease (PKD). If the cysts produce symptomatology owing to their number and size, many palliative treatments are available. When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT). CASE REPORT: A 49-year old woman, diagnosed with PLD and PKD, was listed in January 2008 for combined LT and kidney transplantation (KT). A compatible organ became available 8 months later. Despite preserved liver function, the patient's clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites. At LT, which took 9 hours and was performed using the classic technique, the liver was hard, massive in size (15.5 kg), and not dissociable from the vena cava. The postoperative course was complicated by many septic episodes, the last one being fatal for the patient at 4 months after transplantation. DISCUSSION: LT for PLD in many series shows a high mortality rate. The Model for End-Stage Liver Disease (MELD) score does not stage patients properly, because liver function is usually preserved. The liver can achieve a massive size causing many symptoms, especially malnutrition and ascites; in this setting LT is the only possible treatment. Patients with a low MELD score undergo LT with severe malnutrition that predisposes them to greater susceptibility to sepsis. To identify predictor factors, beyond MELD criteria that relate to the increased liver volume before development of late symptoms is essential to expeditiously treat patients with the poorest prognosis to improve their outcomes.

Microwave thermal ablation for hepatocarcinoma: six liver transplantation cases.

Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has been demonstrated to increase overall survival; however, the majority of patients are not suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for radical treatment of small HCC (<3 cm). It improves 5-year survival compared with standard chemotherapy and chemical ablation, allowing down-staging of unresectable hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was recently introduced in the United States of America and Europe with excellent results, especially with regard to large unresectable HCC. Our single-center experience between May 2009 and October 2010 included application of MWA to 154 patients of median age ± standard deviation of 63.5 ± 8.5 years, 6 males, and 1 female, of mean Model for End-Stage Liver Disease (MELD) score (10.1 ± 3.8). The HCC included, hepatitis C virus (HCV)-related (n=70; 45.5%); alcool (ETOH)-related (n=42; 27%), hepatitis B virus (HBV)-related (n=16; 10.5%); and cryptogenic cases (n=26; 17%). The cases were performed for radical treatment down-staging for multifocal pathology or bridging liver transplantation to orthotopic (OLT) in selected patients with single nodules. A computed tomography (CT) scan was performed at 1 month after the surgical procedure to evalue responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%) showed disease-free survival at one-year follow-up. The radical treatment achieved no intraoperative evidence of tumor spread or of pathological signs of active HCC among the explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to treat HCC and could serve as a "bridge" to OLT and down-staging for patients with HCC.