Islet transplantation for brittle type 1 diabetes: the UIC protocol.

This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1-3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460 080 +/- 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537 495 +/- 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 +/- 0.6 at baseline to 5.6 +/- 0.5 after 2-3 Tx in Group 1 vs. 7.8 +/- 1.1 to 5.8 +/- 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets.

Use of low dose tacrolimus, mycophenolate mofetil and maintenance IL-2 receptor blockade in an islet transplant recipient.

The utilization of dual maintenance therapy with tacrolimus and sirolimus (the Edmonton protocol) has been widely adopted as standard immunosuppression for islet cell transplantation. This immunosuppression regimen has numerous toxicities including renal dysfunction, anemia, and recurrent aphthous ulcers. We present a case of a 63-yr-old Caucasian female who received an isolated islet transplant. Over the first six months post-transplant, the patient developed severe anemia, intractable aphthous ulcers, and renal dysfunction. Islet transplant function was excellent and the patient is insulin-independent since the end of the second month post-transplant. However, because of the above toxicities, a decision was made to change her immunosuppression regimen eight months post-transplant to low dose tacrolimus, mycophenolate mofetil, and a monthly maintenance infusion of daclizumab. Since then, her aphthous ulcers have disappeared, renal function has improved, and islet cell function remains stable.

Obstructive Uropathy because of a Large Rectus Sheath Haematoma: A Case Report of Combined Interventional Radiology and Surgical Approach.

INTRODUCTION: Rectus sheath haematomas associated with anticoagulation are often self limiting. When large, however, they can even extend into the pelvis and cause compression of adjacent organs such as the bladder. A combined endovascular and surgical approach can decrease the operative exposure necessary to treat this occurrence. REPORT: A 42 year old morbidly obese African American female on warfarin treatment for pulmonary embolism presented outside the hospital with pneumonia. During her hospitalisation, she developed a spontaneous right rectus abdominis haematoma below the level of the umbilicus with active bleeding in the extraperitoneal space causing mass compression of the bladder. She developed acute renal failure and became anuric. Following endovascular embolisation of the inferior epigastric artery, surgical exploration was successfully performed to remove the haematoma and relieve the urinary obstruction. Diuresis resumed and renal function normalised without any further evidence of bleeding. DISCUSSION: A large rectus sheath haematoma that extends into the bladder causing renal obstruction can be treated by endovascular embolisation and surgical exploration to limit operative risks and exposure in morbidly obese patients.

Robotic approach to hepatobiliary surgery.

Robot-assisted hepatobiliary surgery has been steadily growing in recent years. It represents an alternative to the open and laparoscopic approaches in selected patients. Endowristed instruments and enhanced visualization provide important advantages in terms of selective bleeding control, microsuturing, and dissection. Cholecystectomies and minor hepatectomies are being performed with comparable results to open and laparoscopic surgery. Even complex procedures, such as major and extended hepatectomies, can have excellent outcomes, in expert hands. The addition of indocyanine green fluorescence provides an additional advantage for recognition of the vascular and biliary anatomy. Future innovations will allow for expanding its use and indications. Robotic surgery has become a very important component of modern minimally invasive surgery and the development of new robotic technology will facilitate a broader adoption of this technique.

Could ICG-aided robotic cholecystectomy reduce the rate of open conversion reported with laparoscopic approach? A head to head comparison of the largest single institution studies.

Comparative studies between robotic and laparoscopic cholecystectomy (LC) focus heavily on economic considerations under the assumption of comparable clinical outcomes. Advancement of the robotic technique and the further widespread use of this approach suggest a need for newer comparison studies. 676 ICG-aided robotic cholecystectomies (ICG-aided RC) performed at the University of Illinois at Chicago (UIC) Division of General, Minimally Invasive and Robotic Surgery were compiled retrospectively. Additionally, 289 LC were similarly obtained. Data were compared to the largest single institution LC data sets from within the US and abroad. Statistically significant variations were found between UIC-RC and UIC-LC in minor biliary injuries (p = 0.049), overall open conversion (p ≤ 0.001), open conversion in the acute setting (p = 0.002), and mean blood loss (p < 0.001). UIC-RC open conversions were also significantly lower than Greenville Health System LC (p ≤ 0.001). Additionally, UIC ICG-RC resulted in the lowest percentages of major biliary injuries (0 %) and highest percentage of biliary anomalies identified (2.07 %). ICG-aided cholangiography and the technical advantages associated with the robotic platform may significantly decrease the rate of open conversion in both the acute and non-acute setting. The sample size discrepancy and the non-randomized nature of our study do not allow for drawing definitive conclusions.

Clinical guidelines as plans--an ontological theory.

OBJECTIVE: Clinical guidelines are special types of plans realized by collective agents. We provide an ontological theory of such plans that is designed to support the construction of a framework in which guideline-based information systems can be employed in the management of workflow in health care organizations. METHOD: The framework we propose allows us to represent, in formal terms, how clinical guidelines are realized through the actions of individuals or ganized into teams. We provide various levels of implementation representing different levels of conformity on the part of health care organizations. RESULT: Implementations built in conformity with our framework are marked by two dimensions of flexibility that are designed to make them more likely to be accepted by health care professionals than standard guideline-based management systems. They do justice to the fact 1) that responsibilities within a health care organization are widely shared, and 2) that health care professionals may on different occasions be non-compliant with guidelines for a variety of well justified reasons. CONCLUSION: The advantage of the framework lies in its built-in flexibility, its sensitivity to clinical context, and its ability to use inference tools based on a robust ontology. One disadvantage lies in its complicated implementation.

[Robotic approach to hepatobiliary surgery. German version]. / Roboterassistierte hepatobiliäre Chirurgie.

Robot-assisted hepatobiliary surgery has been steadily growing in recent years. It represents an alternative to the open and laparoscopic approaches in selected patients. Endowristed instruments and enhanced visualization provide important advantages in terms of selective bleeding control, microsuturing, and dissection. Cholecystectomies and minor hepatectomies are being performed with comparable results to open and laparoscopic surgery. Even complex procedures, such as major and extended hepatectomies, can have excellent outcomes, in expert hands. The addition of indocyanine green fluorescence provides an additional advantage for recognition of the vascular and biliary anatomy. Future innovations will allow for expanding its use and indications. Robotic surgery has become a very important component of modern minimally invasive surgery and the development of new robotic technology will facilitate a broader adoption of this technique.

Neuroendoscopic management of hydrocephalus secondary to midline and pineal lesions.

AIM: In patients with space-occupying lesions of the pineal region, increased intracranial pressure is due to direct compression of the sylvian aqueduct. Based on results of the recent literature, neuroendoscopic management of obstructive hydrocephalus, secondary to tumors of the pineal gland, has gained a preeminent role respect to shunting procedures. METHODS: In 14 select cases, hydrocephalus was secondary to midline and pineal lesions. The patient's age ranged from 1 to 56 years (mean 47.3+/-12.5), with a follow-up ranged from 3 months to 5 years after discharge. In 9 cases the endoscopic procedure represented the only surgical treatment. In 5 cases, microsurgical removal of the lesions and/or ventriculo-peritoneal shunts placement were performed, as additional treatment, while adjuvant radiotherapy was utilized in 4 cases; high dose chemotherapy followed by bone marrow transplantation was performed in 3 cases. RESULTS: In our series, obstructive hydrocephalus secondary to midline and pineal lesions, was successful treated by neuroendoscopic approach alone in 9 cases, with an unremarkable course and good outcome, except in 1 case. CONCLUSIONS: Neuroendoscopic approach affords a minimally invasive way to obtain 4 objectives by one-step surgical approach, such as resolution of obstructive hydrocephalus by endoscopic third ventriculostomy (ETV), cerebrospinal fluid sample to detect tumor markers and to perform cytological analysis, biopsy specimens and tissue diagnosis, associated to absence of shunt-related complications. Therefore, in experienced hands, ETV should be the treatment of first choice, in cases of hydrocephalus secondary to lesions of the pineal gland.

Semantic standards for the representation of medical records.

Physicians developed their sublanguage (a system to represent medical concepts and their relations) to store and transmit general medical knowledge and patient-related information. Adequate formalisms are needed to obtain a standard representation of semantics of medical expressions for computer use. Comparison of the semantic contents of two expressions is possible only if a unique canonical form is defined; the transmission of medical facts or patient-related information is really meaningful only by defining a set of primitives (semantic categories and links) and the domains of values (concepts). These primitives must be harmonized to yield a "common core subset" of semantic categories and links. This subset provides a common basis; a procedure to register extension sets of primitives must also be defined, to comply with specific representation needs of specialties and classes of application software.

High-dose heparin plus warfarin administration in non-traumatic dural sinuses thrombosis. A clinical and neuroradiological study.

BACKGROUND: The management of intracranial dural sinuses thrombosis is still controversial and uncertain. The authors report the cases of 7 patients with non-traumatic thrombosis of the dural sinuses and describe the most important radiographic findings, the indication, effectiveness of antithrombotic therapy, and outcome. METHODS: A retrospective review was conducted of 7 cases of dural sinus thrombosis admitted, between 1994 and 1996, to our division. All patients underwent full anticoagulation therapy. Heparin was administered, using a dose of 25,000 units/day for two weeks; warfarin was given using a dose of 5 mg twice daily. Treatment course was followed by maintenance treatment with a single administration of 5 mg/day of warfarin. All patients were submitted to close titration and coagulation profile monitoring. RESULTS: In 4 cases Magnetic Resonance Imaging-Angiography (Angio-MRI) was performed for following up the recanalization of the sinuses, resulting a persistent no patency of the dural sinuses. Three patients underwent contrast-enhanced CT scan, demonstrated an "empty delta sign" in the sagittal sinus, confirming no recanalization. Nevertheless, six patients had have a good quality recovery, and one patient a moderate disability. DISCUSSION: Cerebral venous sinus thrombosis is an uncommon cause of cerebral infarction, and may be mistaken, unless specifically sought. The natural history of the disease is highly variable, with a mortality rates range from 10% to 20%. At present, in our opinion, the venous phase of Angio-MRI is the definitive examination, and a gold standard for diagnosis of dural sinus thrombosis. In our cases, antithrombotic therapy has been found to be a safe and effective treatment, despite contrast-CT scans and Angio-MRI showed no recanalization of the sinuses, in all patients.

Operational intelligence and school problems measured by Piagetian tasks and Rhode Island Pupil Identification Scale.

To explore the relations between operational intelligence rated on several Piagetian tasks and school learning problems identified by the Rhode Island Pupil Identification Scale by Novack, Bonaventura, and Merenda we assumed that Piagetian performances would allow predicting learning problems of first graders. 38 pupils were evaluated by three teachers, who were asked to complete the Rhode Island scale. Then the same children were individually given 8 Piagetian tests (including conservation and logical tasks) by an examiner who had no information about the pupils' other scores. Analysis showed that successful Piagetian performances were associated with ratings of successful schoolwork. Analysis of variance confirmed that difficulties in operational reasoning predict occurrence of learning problems. We concluded that operational intelligence and school learning in children are closely related.

[Spinal cord infarction during haemodialysis]. / Infarto del midollo spinale in un paziente con insufficienza renale cronica in emodialisi con estese calcificazioni cardiovascolari.

A 26-year-old patient with chronic renal failure presented a spinal cord infarction during haemodialysis. This is the first case of a patient with chronic renal failure maintained on chronic haemodialysis described in literature. In this case, the severity of vascular lesions documented by widespread vascular calcifications were particularly striking.

Improved outcomes in islet isolation and transplantation by the use of a novel hemoglobin-based O2 carrier.

During isolation, islets are exposed to warm ischemia. In this study, intraductal administration of oxygenated polymerized, stroma-free hemoglobin-pyridoxalated (Poly SFH-P) was performed to improve O2 delivery. Rat pancreata subjected to 30-min warm ischemia were perfused intraductally with collagenase in oxygenated Poly SFH-P/RPMI or RPMI (control). PO2 was increased by Poly SFH-P (381.7 +/- 35.3 mmHg vs. 202.3 +/- 28.2, p = 0.01) and pH maintained within physiological range (7.4-7.2 vs. 7.1-6.6, p = 0.009). Islet viability (77% +/- 4.6 vs. 63% +/- 4.7, p = 0.04) was improved and apoptosis lower with Poly SFH-P (caspase-3: 34,714 +/- 2167 vs. 45,985 +/- 1382, respectively, p = 0.01). Poly SFH-P improved islet responsiveness to glucose as determined by increased intracellular Ca2+ levels and improved insulin secretion (SI 5.4 +/- 0.1 vs. 3.1 +/- 0.2, p = 0.03). Mitochondrial integrity was improved in Poly SFH-P-treated islets, which showed higher percentage change in membrane potential after glucose stimulation (14.7% +/- 1.8 vs. 9.8 +/- 1.4, respectively, p < 0.05). O2 delivery by Poly SFH-P did not increase oxidative stress (GSH 7.1 +/- 2.9 nm/mg protein for Poly SFH-P vs. 6.8 +/- 2.4 control, p = 0.9) or oxidative injury (MDA 1.8 +/- 0.9 nmol/mg protein vs. 6.2 +/- 2.4, p = 0.19). Time to reach normoglycemia in transplanted diabetic nude mice was shorter (1.8 +/- 0.4 vs. 7 +/- 2.5 days, p = 0.02), and glucose tolerance improved in the Poly SFH-P group (AUC 8106 +/- 590 vs. 10,863 +/- 946, p = 0.03). Oxygenated Poly SFH-P improves islet isolation and transplantation outcomes by preserving mitochondrial integrity.

Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation.

Oxidative stress during islet isolation induces a cascade of events injuring islets and hampering islet engraftment. This study evaluated islet isolation and transplantation outcomes after intra-ductal glutamine administration. Human pancreata deemed unsuitable for pancreas or islet transplantation were treated with either a 5 mM solution of l-glutamine (n = 6) or collagenase enzyme alone (n = 6) through the main pancreatic duct. Islet yield, viability, in vitro function; markers of oxidative stress [malondialdehyde (MDA) and Glutathione (GSH)] and apoptosis were assessed. Islet yields were significantly increased in the glutamine group compared to controls (318, 559 +/- 25, 800 vs. 165, 582 +/- 39, 944 mean +/- SEM, p < 0.01). The amount of apoptotic cells per islet was smaller in the glutamine group than the control. The percentage of nude mice rendered normoglycemic with glutamine-treated islets was higher than the controls (83% n = 10/12 vs. 26% n = 6/23; p < 0.01), and the time to reach normoglycemia was decreased in the glutamine group (1.83 +/- 0.4 vs. 7.3 +/- 3 days; p < 0.01). Glutamine administration increased GSH levels (7.6 +/- 1.7 nmol/mg protein vs. 4.03 +/- 0.5 in control, p < 0.05) and reduced lipid-peroxidation (MDA 2.45 +/- 0.7 nmol/mg of protein vs. 6.54 +/- 1.7 in control; p < 0.05). We conclude that intra-ductal administration of glutamine reduces oxidative injury and apoptosis and improves islet yield and islet graft function after transplantation.

Cognitive design for sharing medical knowledge models.

By building a medical conceptual model inside the galen project, a methodology has been defined to deal with both operative goals and deep and unsolved problems about knowledge. This knowledge sharing oriented approach exploits existing medical coding systems such as knowledge sources and enables us to represent their concepts in a wider cognitive context referring to ontological theories. The tasks of cognitive ergonomy, quasi-naturalness of language, versatility, and flexibility seem to be supported through some functions, such as viewpoint, context, and sign, which act as spin-off points to knowledge or information which is not modeled.

An ontological analysis of the UMLS Metathesaurus.

Paper-based terminology systems cannot satisfy anymore the new desiderata of healthcare information systems: the demand for re-use and sharing of patient data, their transmission and the need of semantic-based criteria for purposive statistical aggregation. The unambiguous communication of complex and detailed medical concepts is now a crucial feature of medical information systems. Ontologies can support a more effective data and knowledge sharing in medicine. In this paper we briefly survey our ontological analysis and integration of various top-levels of terminologies and we report the main results of the ontological analysis of the UMLS Metathesaurus.

Toward a standard for guideline representation: an ontological approach.

Guidelines for clinical practice are being introduced in an extensive way in more and more different fields of medicine They have the potentialities of improving the quality and cost-efficiency of care in an increasingly complex health care delivery environment. Computerization may increase the effectiveness of both the information retrieval of guidelines and the management of guideline-based care. The scenario is evolving from stand-alone workstations to telematics applications that enable guidelines development and dissemination. However, such a knowledge sharing requires the definition of formal models for guidelines representation. The models should have a clear semantics in order to avoid ambiguities. The role of ontologies is that of making explicit the conceptualizations behind a model. In this paper we present our library of ontologies and point out its role for integrating existing guideline models and defining standard representations.

WWW-available conceptual integration of medical terminologies: the ONIONS experience.

We present the most applicable aspects of our research in the conceptual integration of terminologies. From past experience, we claim that the conceptualizations provided for terminological ontologies need to be philosophically and linguistically grounded. We developed ONIONS, a methodology for integrating domain terminologies by exploiting a library of generic ontologies. Our current focus is on flexible and cooperative modelling of terminological ontologies. We adopt modular and negotiable architectures of ontologies and some WWW-oriented tools, such as Ontolingua and Ontosaurus.

Understanding systematic conceptual structures in polysemous medical terms.

Polysemy is a bottleneck for the demanding needs of semantic data management. We suggest the importance of a well-founded conceptual analysis for understanding some systematic structures underlying polysemy in the medical lexicon. We present some cases studies, which exploit the methods (ontological integration and general theories) and tools (description logics and ontology libraries) of the ONIONS methodology defined elsewhere by the authors. This paper addresses an aspect (systematic metomymies) of the project we are involved in, which investigates the feasibility of building a large-scale ontology library of medicine that integrates the most important medical terminology banks.

Role of transarterial chemoembolization before liver resection for hepatocarcinoma.

The aim of this study was to clarify whether chemoembolization (TACE) before liver resection (LR) can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve disease-free and overall survival. Eighty-nine patients with tumor-stage (TNM) I-II HCC were evaluated for LR. Patients were prospectively allocated to LR alone or TACE plus LR based on their place of residence. Twenty nonlocal patients (24%) were selected for LR, while 69 (77.5%) local patients were selected for TACE plus LR. Following TACE, the tumor stage could be confirmed in only 20 patients (29%) who then underwent LR. Operative mortality was 0%, but in the TACE-LR group, 3 patients died of liver failure between 2 and 5 months after surgery. Early recurrence (<24 months) was 59% for LR versus 20% for TACE plus LR (P <.05). Late recurrence was 18% for LR versus 10% for TACE plus LR (P = not significant [NS]). The overall recurrence rate was 76% for LR versus 30% for TACE plus LR (P <.02). Death due to HCC recurrence was 70% for LR versus 15% for TACE plus LR (P <.05). The overall 1- and 5-year survival rates did not differ significantly (71% to 38% for LR v 85% to 43% for TACE + LR; P = NS), whereas the difference in 1- and 5-year disease-free survival was highly significant (64% to 21% for LR v 82% to 57% for TACE + LR; P <.02). TACE was able to improve the HCC staging process and significantly reduce the incidence of early and overall HCC recurrence and related death after LR; it improved the disease-free interval, but not the overall survival, due to an increase in liver failure in the first 5 months.