Acute Lower Extremity Fracture Management in Chronic Spinal Cord Injury: 2022 Delphi Consensus Recommendations.

Our objective was to develop a clinical practice guideline (CPG) for the treatment of acute lower extremity fractures in persons with a chronic spinal cord injury (SCI). Methods: Information from a previous systematic review that addressed lower extremity fracture care in persons with an SCI as well as information from interviews of physical and occupational therapists, searches of the literature, and expert opinion were used to develop this CPG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to determine the quality of evidence and the strength of the recommendations. An overall GRADE quality rating was applied to the evidence. Conclusions: Individuals with a chronic SCI who sustain an acute lower extremity fracture should be provided with education regarding the risks and benefits of operative and nonoperative management, and shared decision-making for acute fracture management should be used. Nonoperative management historically has been the default preference; however, with the advent of greater patient independence, improved surgical techniques, and advanced therapeutics and rehabilitation, increased use of surgical management should be considered. Physical therapists, kinesiotherapists, and/or occupational therapists should assess equipment needs, skills training, and caregiver assistance due to changes in mobility resulting from a lower extremity fracture. Therapists should be involved in fracture management as soon as possible following fracture identification. Pressure injuries, compartment syndrome, heterotopic ossification, nonunion, malunion, thromboembolism, pain, and autonomic dysreflexia are fracture-related complications that clinicians caring for patients who have an SCI and a lower extremity fracture may encounter. Strategies for their treatment are discussed. The underlying goal is to return the patient as closely as possible to their pre-fracture functional level with operative or nonoperative management.

Long-term effects of bilateral pallidal deep brain stimulation in dystonia: a follow-up between 8 and 16 years.

OBJECTIVE: Observational study to evaluate the long-term motor and non-motor effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on medically refractory dystonia. BACKGROUND: Dystonia is a chronic disease affecting mainly young patients with a regular life expectancy and lifelong need for therapy. Pallidal DBS is an established treatment for severe isolated dystonia but long-term data are sparse. METHODS: We considered 36 consecutive patients with isolated generalized (n = 14) and cervical/segmental (n = 22) dystonia operated at Charité-University Hospital between 2000 and 2007 in a retrospective analysis for long-term outcome of pallidal DBS. In 19 of these patients, we could analyze dystonic symptoms and disability rated by the Burke-Fahn-Marsden Dystonia Rating scale (BFMDRS) at baseline, short-term (ST-FU, range 3-36 months) and long-term follow-up (LT-FU, range 93-197 months). Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires. RESULTS: Patients reached an improvement in motor symptoms of 63.8 ± 5.7% (mean ± SE) at ST-FU and 67.9 ± 6.1% at LT-FU. Moreover, a significant and stable reduction in disability was shown following DBS (54.2 ± 9.4% at ST-FU and 53.8 ± 9.2% at LT-FU). BDI and SF36 had improved by 40% and 23%, respectively, at LT-FU (n = 14). Stimulation-induced adverse events included swallowing difficulties, dysarthria, and bradykinesia. Pulse generator (n = 3) and electrodes (n = 5) were revised in seven patients due to infection. CONCLUSIONS: Pallidal DBS is a safe and efficacious long-term treatment for dystonia with sustained effects on motor impairment and disability, accompanied by a robust improvement in mood and quality of life.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

[Rehabilitation after Traumatic Fracture of Thoracic and Lumbar Spine]. / Rehabilitation nach traumatischen Frakturen der Brust- und Lendenwirbelsäule.

On the basis of the S2-k guideline "Rehabilitation after traumatic fractures of the thoracic und lumbar spine without neurologic disorder", this article gives an overview of target-oriented rehabilitation of patients with minor fractures or those with column stability and unstable spinal fractures which are stabilised by surgery. To obtain early social and job related reintegration, outpatient or inpatient rehabilitation has to start immediately after treatment in hospital. Rehabilitation must be orientated towards the biopsychosocial model of ICF and has to be adapted for the patient. The overall goal of rehabilitation is functional restoration of patient health to enable participation in society, life and job. Individual goals may change during rehabilitation, because of differential progress in therapy. Pain management must be orientated towards individual requirements and mental health has to be tested early, especially in polytrauma patients. Disorders have to be treated by psychotherapy, because psychic stress supports chronification of pain. Generally early exercise and physiotherapy are recommended in the guideline, with patient education for health-seeking behavior. Otherwise an orthesis device is not really necessary for treatment of a stable fracture. To improve the outcome of rehabilitation aftercare, treatment has to be arranged during rehabilitation, especially for employed patients.

Making strong polyelectrolyte brushes pH-sensitive by incorporation of gold nanoparticles.

Doping polymer brushes with gold nanoparticles (AuNPs) results in composite materials with colorimetric sensor properties. The present paper addresses the effect of electrostatic particle-particle interaction and the effect of the polymer brush type on particle assembly formation within the polymer matrix. The prospect for long-term use as colorimetric sensors is tested. Therefore, two different types of brushes of pH-insensitive polymers, non-ionic poly(N-isopropylacrylamide) (PNIPAM) and cationic poly-[2-(methacryloyloxy)ethyl] trimethylammonium chloride (PMETAC), are studied. After incubation of the non-ionic PNIPAM brush in an aqueous suspension of AuNPs with a pH-sensitive carboxylic acid capping, hydrogen binding led to attachment of the AuNPs, but they were easily detached at high pH due to loss of the hydrogen binding. In contrast, the anionic AuNPs adhere well to cationic PMETAC brushes even after post-treatment at low pH where the charge density of the AuNPs is strongly reduced. Therefore, the PMETAC/AuNP composites were further tested with respect to their stability against pH variations and their impact for colorimetric sensors. Although the neat PMETAC brush is not pH-sensitive, after embedding pH-sensitive AuNPs, the PMETAC/AuNP composite becomes pH-sensitive in a reversible manner. This is detectable by the reversible shift of the plasmon band and the reversible thickness change of the composites by exposing them to different pH.

Carcinoma adenoide quístico de cavidad nasal y senos paranasales: experiencia de 5 años en Clínica Las Condes de Santiago de Chile / Adenoid cystic carcinoma of nasal cavity and paranasal sinuses: 5 years experience in las Condes Clinic of Santiago of Chile

RESUMEN Introducción: El carcinoma adenoide quístico es una neoplasia originada en glándulas exocrinas de todo el cuerpo, principalmente en glándulas salivales mayores. En cavidad nasal y senos paranasales es poco frecuente y se caracteriza por presentar una alta frecuencia de recurrencia y de metástasis a distancia posterior a su remisión y a pesar de su tratamiento. Objetivo: Describir características de una serie de casos de pacientes con carcinoma adenoide quístico de cavidad nasal y senos paranasales operados. Material y método: Estudio descriptivo-retrospectivo. Período enero de 2012 y enero de 2017. La información se obtuvo a partir de las fichas electrónicas de la Clínica Las Condes. Se describen procedencia, edad y sexo, características clínicas, hallazgos anatomopatológicos, métodos diagnósticos, tratamiento, evolución. Resultados: Total de 5 pacientes operados, 3 mujeres y 2 hombres. La edad promedio fue de 63 años, con rango de 33 años a 90 años de edad. 100% de los casos sin factores asociados. La presentación clínica más frecuente fue la obstrucción nasal unilateral, seguida por el dolor facial. Dos pacientes se presentaron con diagnóstico inicial, dos por recurrencia y uno por persistencia. En tres casos el tumor se origina de seno maxilar y en dos en seno etmoidal. Todos presentaron enfermedad avanzada, etapa IV y III. Tres pacientes histológicamente fueron de bajo grado y dos de alto grado. En los cinco casos el tratamiento primario fue quirúrgico, en el 60% endoscópico, 20% abierto y 20% combinado. En cuatro casos se usó radioterapia posoperatoria y en tres de éstos, quimioterapia concomitante. Todos se encuentran sin signos de recidiva tumoral en último control. Conclusiones: El carcinoma adenoide quístico de cavidad nasal y senos paranasales es bastante infrecuente, su incidencia es menor a 1/100.000 casos por año. Es más frecuente en mujeres entre 40 y 50 años. Se identifica más con su origen en el seno maxilar (50%) y de patrón cribiforme. Clínicamente se presenta en estadíos avanzados ya que en etapa precoz es asintomático o presenta clínica inespecífica inflamatoria. El diagnóstico se realiza con biopsia complementada con imagenología. El tratamiento más utilizado es la cirugía endoscópica o abierta asociado a radioterapia posoperatoria, a pesar de la cual, se presentan con alta recurrencia a largo plazo.

ABSTRACT Introduction: Adenoid Cystic Carcinoma is a neoplasm originating in exocrine glands throughout the body, mainly in the major salivary glands. In the nasal cavity and paranasal sinuses is rare and characterized by a high frequency of recurrence and distant metastasis after remission and despite its treatment. Aim: To describe characteristics of a series of patients with operated adenoid cystic carcinoma of the nasal cavity and paranasal sinuses. Material and method: Descriptive-retrospective study. Period January 2012 and January 2017. The information was obtained from the electronic tabs of the Las Condes Clinic. It describes origin, age and sex, clinical characteristics, anatomopathological findings, diagnostic methods, treatment, evolution. Results: Total 5 patients operated, 3 women and 2 men. The average age was 63 years, ranging from 33 years to 90 years of age. 100% of the cases without associated factors. The most frequent clinical presentation was unilateral nasal obstruction, followed by facial pain. 2 patients presented with initial diagnosis, 2 due to recurrence and 1 due to persistence. In 3 cases the tumor originates from the maxillary sinus and in 2 in the ethmoidal sinus. All had advanced disease, stage IV and III. 3 patients were histologically low grade and 2 high grade. In all 5 cases, the primary treatment was surgical, 60% endoscopic, 20% open and 20% combined. In 4 cases, postoperative radiotherapy was used and in 3 of this concomitant chemotherapy. All are without signs of tumor recurrence in the last control. Conclusion: Adenoid Cystic Carcinoma of the nasal cavity and paranasal sinuses is quite infrequent; its incidence is less than 1/100,000 cases per year. It is more common in women between 40 and 50 years. It is identified more with its origin in the maxillary sinus (50%) and cribriform pattern. Clinically it presents in advanced stages since at an early stage, it is asymptomatic or it presents nonspecific inflammatory clinic. Diagnosis is performed with biopsy supplemented with imaging. The most commonly used treatment is endoscopic or open surgery associated with postoperative radiotherapy, despite which, they present with high recurrence in the long term.

The internal structure of PMETAC brush/gold nanoparticle composites: a neutron and X-ray reflectivity study.

This work addresses the pH-triggered distribution and relocation of charge-stabilized gold nanoparticles (AuNPs) incorporated into strong polyelectrolyte brushes. Brush/particle composite materials were investigated under aqueous conditions and at different humidities using neutron and X-ray reflectivity, respectively. X-ray reflectivity measurements complement neutron reflectivity measurements and reveal results that could not be observed by neutron reflectivity measurements. Both methods allow scanning the particle density profile, but due to different contrasts, they are sensitive to different regions within the brush. More specifically, 3-mercaptopropionic acid (MPA)-coated AuNPs were incorporated into poly-[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PMETAC) polyelectrolyte brushes at different pH values. The pH value triggers a change in the AuNP surface charge caused by the pH-sensitivity of the MPA ligands, while the charge of the PMETAC brush is not affected by pH variations. The particle number density as well as the particle distribution depend strongly on the pH value of the incubation medium: a rather non-homogeneous assembly (2D assembly) is found when the PMETAC brush is incubated in AuNP suspension at pH 4, while a more homogeneous assembly (3D assembly) is found when the PMETAC brush is incubated in AuNP suspension at pH 8. The main factor dominating the formation of 2D or 3D assembly is assigned to the particle-particle interaction and not to the particle-polymer interaction. No significant relocation of AuNPs within the brush can be found by changing the environmental conditions. The control of particle amount and distribution within the polymer brush has a strong impact on the optical properties of those composite materials, which is crucial for the fabrication of colorimetric sensors.

Estenosis de la apertura piriforme y síndrome de incisivo central único: casos clínicos / Piriform aperture stenosis and solitary median maxillary central incisor: clinical cases

El síndrome incisivo central único es un trastorno que involucra anomalías de la línea media. Se puede presentar con dificultad respiratoria poniendo en peligro la vida del recién nacido, debido a malformaciones nasales. Estas malformaciones incluyen atresia de coanas y la estenosis de la apertura del orificio piriforme. Debe pensarse en esta última en todo recién nacido con estridor y dificultad respiratoria de grado variable, asociado a la dificultad de pasar una sonda a través de la región anterior de las fosas nasales. El diagnóstico se confirma por tomografía computarizada del macizo craneofacial y el examen nasofibroscópico. La conducta terapéutica dependerá de la gravedad de los síntomas, pero en general si es que no hay compromiso respiratorio severo, se prefiere una conducta expectante, y esperar el crecimiento craneofacial del niño, para aumentar permeabilidad nasal. Presentamos dos casos clínicos.

Solitary median maxillary central incisor syndrome is a rare disorder involving midline abnormalities. It may present with life threatening respiratory distress in the neonate secondary to nasal malformations. These include choanal atresia and pyriform aperture stenosis. The last to be thought in any newborn with stridor and respiratory distress associated with the difficulty of passing a tube through the anterior region of the nostrils. The diagnosis is confirmed by craniofacial CT scan and nasolaryngoscope evaluation. The therapeutic approach depends on the severity of symptoms.

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM).

BACKGROUND: Data on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We seek to systematically evaluate the clinical outcome of paediatric patients undergoing DBS. METHODS: A German registry on paediatric DBS (GEPESTIM) was created to collect data of patients with dystonia undergoing DBS up to the age of 18 years. Patients were divided into three groups according to etiology (group 1 inherited, group 2 acquired, and group 3 idiopathic dystonia). RESULTS: Data of 44 patients with a mean age of 12.8 years at time of operation provided by 6 German centers could be documented in the registry so far (group 1 n = 18, group 2 n = 16, group 3 n = 10). Average absolute improvement after implantation was 15.5 ± 18.0 for 27 patients with pre- and postoperative Burke-Fahn-Marsden Dystonia Rating scale movement scores available (p < 0.001) (group 1: 19.6 ± 19.7, n = 12; group 2: 7.0 ± 8.9, n = 8; group 3: 19.2 ± 20.7, n = 7). Infection was the main reason for hardware removal (n = 6). 20 IPG replacements due to battery expiry were necessary in 15 patients at 3.7 ± 1.8 years after last implantation. DISCUSSION: Pre- and postoperative data on paediatric DBS are very heterogeneous and incomplete but corroborate the positive effects of DBS on inherited and acquired dystonia. Adverse events including relatively frequent IPG replacements due to battery expiry seem to be a prominent feature of children with dystonia undergoing DBS. The registry enables collaborative research on DBS treatment in the paediatric population and to create standardized management algorithms in the future.

Long-term results of deep brain stimulation in a cohort of eight children with isolated dystonia.

Pallidal deep brain stimulation (DBS) is an established treatment for patients with severe isolated dystonia. However, clinical evidence for the long-term use of DBS in children is limited and controlled trials have not yet been conducted. Here, we provide the long-term results of up to 13 years of pallidal DBS in eight pediatric patients with generalized idiopathic or hereditary isolated dystonia (five males, mean age at surgery 12.5 ± 3.5 years), as assessed by retrospective video rating. Video rating was performed at three time points: pre-operative, 1-year short-term follow-up (1y-FU) and long-term last FU (LT-FU, up to 13 years). Symptom severity and disability were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Disability scores were obtained from clinical charts and during the last FU. The mean improvement in BFMDRS motor score was 54.4 ± 8.9 % at 1y-FU and 42.9 ± 11.6 % at LT-FU; the disability scores improved by 59.8 ± 10.3 and 63.3 ± 7.8 %, respectively. Electrode dislocation was noted in one patient and implantable pulse generator dislocation in another, both requiring surgical intervention; no further serious adverse events occurred. Our study presents the first blinded video rating assessment of the short- and long-term effects of pallidal DBS in children with idiopathic or hereditary isolated dystonia. Results confirm that pallidal DBS is a safe and efficacious long-term treatment in children, with overall motor improvement similar to that described in controlled trials in adults.

Uso del láser CO2 en la cirugía de la disfagia cricofaríngea: caso clínico / CO2 Laser use in the surgery of the cricopharyngeal muscle dysfunction: case report

La miotomía cricofaríngea es una técnica quirúrgica introducida hace años para el tratamiento de la disfagia asociada a disfunción del músculo cricofaríngeo con o sin divertículo de Zenker, mostrando resultados exitosos que revierten la sintomatologta y mejoran la calidad de vida del paciente. Con los avances científicos surge la cirugía láser endoscópica que permite ser una alternativa quirúrgica segura, viable y efectiva respecto a la miotomía clásica abierta, según diferentes series publicadas, mostrando disminuir los tiempos de anestesia, quirúrgico y de recuperación. En este artículo describimos un caso clínico, la técnica quirúrgica utilizada y los resultados en un paciente con disfagia por disfunción cricofaríngea con buen resultado posoperatorio.

Cricopharyngeal myotomy is a surgical technique introduced years ago for the treatment of dysphagia associated with cricopharyngeal muscle dysfunction with or without Zenker’s diverticulum, showing successful results that reverse the symptoms and improve the quality of life of patients. With scientific advances endoscopic laser surgery allows to be an open safe, feasible and effective for classical surgical myotomy alternative, according to various published series showing decreasing times anesthesia, surgical and recovery emerges. In this article we describe a case, the surgical technique used and results in a patient with dysphagia by cricopharyngeal dysfunction with good postoperative outcome.

Long-term effect on dystonia after pallidal deep brain stimulation (DBS) in three members of a family with a THAP1 mutation.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment in patients with severe dystonia. However, factors predicting outcome are largely unknown and motor improvement in DYT6 patients after DBS has been reported to be poorer as compared to, e.g., DYT1 patients. Here, we report the course of clinical improvement for up to 11 years of pallidal DBS in three male patients belonging to the same family with early-onset generalized or segmental dystonia due to a heterozygous THAP1 gene mutation (DYT6). All patients showed an initial effective response to pallidal DBS with a mean of 56.9 ± 11.7% improvement in the Burke-Fahn-Marsden Dystonia motor and 45.5 ± 22.4% in the disability score at 1-year follow-up. The long-term outcome of pallidal DBS was favorable in two patients (39, 67% motor improvement, respectively). Our findings demonstrate that motor improvement is variable and may depend on disease severity, disease duration, and clinical presentation. Overall, our observation supports pallidal DBS as an important treatment option in patients with DYT6 dystonia.

Borrelia miyamotoi infection in nature and in humans.

Borrelia miyamotoi is a relapsing fever Borrelia group spirochete that is transmitted by the same hard-bodied (ixodid) tick species that transmit the agents of Lyme disease. It was discovered in 1994 in Ixodes persulcatus ticks in Japan. B. miyamotoi species phylogenetically cluster with the relapsing fever group spirochetes, which usually are transmitted by soft-bodied (argasid) ticks or lice. B. miyamotoi infects at least six Ixodes tick species in North America and Eurasia that transmit Lyme disease group spirochetes and may use small rodents and birds as reservoirs. Human cases of B. miyamotoi infection were first reported in 2011 in Russia and subsequently in the United States, Europe and Japan. These reports document the public health importance of B. miyamotoi, as human B. miyamotoi infection appears to be comparable in frequency to babesiosis or human granulocytic anaplasmosis in some areas and may cause severe disease, including meningoencephalitis. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Symptoms of B. miyamotoi infection generally resolve within a week of the start of antibiotic therapy. B. miyamotoi infection should be considered in patients with acute febrile illness who have been exposed to Ixodes ticks in a region where Lyme disease occurs. Because clinical manifestations are nonspecific, etiologic diagnosis requires confirmation by blood smear examination, PCR, antibody assay, in vitro cultivation, and/or isolation by animal inoculation. Antibiotics that have been used effectively include doxycycline for uncomplicated B. miyamotoi infection in adults and ceftriaxone or penicillin G for meningoencephalitis.

Big Data Usage Patterns in the Health Care Domain: A Use Case Driven Approach Applied to the Assessment of Vaccination Benefits and Risks. Contribution of the IMIA Primary Healthcare Working Group.

BACKGROUND: Generally benefits and risks of vaccines can be determined from studies carried out as part of regulatory compliance, followed by surveillance of routine data; however there are some rarer and more long term events that require new methods. Big data generated by increasingly affordable personalised computing, and from pervasive computing devices is rapidly growing and low cost, high volume, cloud computing makes the processing of these data inexpensive. OBJECTIVE: To describe how big data and related analytical methods might be applied to assess the benefits and risks of vaccines. METHOD: We reviewed the literature on the use of big data to improve health, applied to generic vaccine use cases, that illustrate benefits and risks of vaccination. We defined a use case as the interaction between a user and an information system to achieve a goal. We used flu vaccination and pre-school childhood immunisation as exemplars. RESULTS: We reviewed three big data use cases relevant to assessing vaccine benefits and risks: (i) Big data processing using crowdsourcing, distributed big data processing, and predictive analytics, (ii) Data integration from heterogeneous big data sources, e.g. the increasing range of devices in the "internet of things", and (iii) Real-time monitoring for the direct monitoring of epidemics as well as vaccine effects via social media and other data sources. CONCLUSIONS: Big data raises new ethical dilemmas, though its analysis methods can bring complementary real-time capabilities for monitoring epidemics and assessing vaccine benefit-risk balance.

Increased growth of colorectal liver metastasis following partial hepatectomy.

Nearly 50 % of colorectal cancer (CRC) patients develop liver metastases with liver resection being the only option to cure patients. Residual micrometastases or circulating tumor cells are considered a cause of tumor relapse. This work investigates the influence of partial hepatectomy (PH) on the growth and molecular composition of CRC liver metastasis in a syngeneic rat model. One million CC531 colorectal tumor cells were implanted via the portal vein in WAG/Rij rats followed by a 30 % PH a day later. Control groups either received tumor cells followed by a sham-operation or were injected with a buffer solution followed by PH. Animals were examined with magnetic resonance imaging (MRI) and liver tissues were processed for immunolabeling and PCR analysis. One-third PH was associated with an almost threefold increase in relative tumor mass (MRI volumetry: 2.8-fold and transcript levels of CD44: 2.3-fold). Expression of molecular markers for invasiveness and aggressiveness (CD49f, CXCR4, Axin2 and c-met) was increased following PH, however with no significant differences when referring to the relative expression levels (relating to tumor mass). Liver metastases demonstrated a significantly higher proliferation rate (Ki67) 2 weeks following PH and cell divisions also increased in the surrounding liver tissue. Following PH, the stimulated growth of metastases clearly exceeded the compensation in liver volume with long-lasting proliferative effects. However, the distinct tumor composition was not influenced by liver regeneration. Future investigations should focus on the inhibition of cell cycle (i.e. systemic therapy strategies, irradiation) to hinder liver regeneration and therefore restrain tumor growth.

Business Process Modelling is an Essential Part of a Requirements Analysis. Contribution of EFMI Primary Care Working Group.

OBJECTIVES: To perform a requirements analysis of the barriers to conducting research linking of primary care, genetic and cancer data. METHODS: We extended our initial data-centric approach to include socio-cultural and business requirements. We created reference models of core data requirements common to most studies using unified modelling language (UML), dataflow diagrams (DFD) and business process modelling notation (BPMN). We conducted a stakeholder analysis and constructed DFD and UML diagrams for use cases based on simulated research studies. We used research output as a sensitivity analysis. RESULTS: Differences between the reference model and use cases identified study specific data requirements. The stakeholder analysis identified: tensions, changes in specification, some indifference from data providers and enthusiastic informaticians urging inclusion of socio-cultural context. We identified requirements to collect information at three levels: micro- data items, which need to be semantically interoperable, meso- the medical record and data extraction, and macro- the health system and socio-cultural issues. BPMN clarified complex business requirements among data providers and vendors; and additional geographical requirements for patients to be represented in both linked datasets. High quality research output was the norm for most repositories. CONCLUSIONS: Reference models provide high-level schemata of the core data requirements. However, business requirements' modelling identifies stakeholder issues and identifies what needs to be addressed to enable participation.

Use of a novel virus detection assay to identify coronavirus HKU1 in the lungs of a hematopoietic stem cell transplant recipient with fatal pneumonia.

A 38-year-old female patient with systemic lupus erythematosus presented with pulmonary infiltrates and hypoxemia for several months following immunodepleting autologous hematopoietic stem cell transplantation. She was treated for influenza, which was isolated repeatedly from oropharynx and bronchoalveolar lavage (BAL) fluids, and later empirically for lupus pneumonitis, but died 6 months after transplant. Autopsy findings failed to show influenza in the lungs or lupus pneumonitis. A novel generic polymerase chain reaction (PCR)-based assay using degenerate primers identified human coronavirus (CoV) HKU1 RNA in BAL fluid at autopsy. CoV was confirmed by virus-specific PCRs of lung tissue at autopsy. Electron microscopy showed viral particles consistent with CoV HKU1 in lung tissue both at autopsy and from a previous biopsy. Although human CoV HKU1 infection is not usually severe, in highly immunocompromised patients, it can be associated with fatal pneumonia.

Key concepts to assess the readiness of data for international research: data quality, lineage and provenance, extraction and processing errors, traceability, and curation. Contribution of the IMIA Primary Health Care Informatics Working Group.

OBJECTIVE: To define the key concepts which inform whether a system for collecting, aggregating and processing routine clinical data for research is fit for purpose. METHODS: Literature review and shared experiential learning from research using routinely collected data. We excluded socio-cultural issues, and privacy and security issues as our focus was to explore linking clinical data. RESULTS: Six key concepts describe data: (1) DATA QUALITY: the core Overarching concept - Are these data fit for purpose? (2) Data provenance: defined as how data came to be; incorporating the concepts of lineage and pedigree. Mapping this process requires metadata. New variables derived during data analysis have their own provenance. (3) Data extraction errors and (4) Data processing errors, which are the responsibility of the investigator extracting the data but need quantifying. (5) Traceability: the capability to identify the origins of any data cell within the final analysis table essential for good governance, and almost impossible without a formal system of metadata; and (6) Curation: storing data and look-up tables in a way that allows future researchers to carry out further research or review earlier findings. CONCLUSION: There are common distinct steps in processing data; the quality of any metadata may be predictive of the quality of the process. Outputs based on routine data should include a review of the process from data origin to curation and publish information about their data provenance and processing method.

Regional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation.

Hepatocyte transplantation is regarded as a promising option to correct hereditary metabolic liver disease. This study describes a novel method involving regional transient portal ischemia (RTPI) in combination with hepatic irradiation (IR) as a preparative regimen for hepatocyte transplantation. The right lobules of rat livers (45% of liver mass) were subjected to RTPI of 30-120 min. Liver specimens and serum samples were analyzed for transaminase levels, DNA damage, apoptosis, and proliferation. Repopulation experiments involved livers of dipeptidylpeptidase IV (DPPIV)-deficient rats preconditioned with RTPI (60-90 min) either with or without prior partial hepatic IR (25 Gy). After reperfusion intervals of 1 and 24 h, 12 million wild-type (DPPIV positive) hepatocytes were transplanted into recipient livers via the spleen. RTPI of 60-90 min caused limited hepatic injury through necrosis and induced a distinct regenerative response in the host liver. Twelve weeks following transplantation, small clusters of donor hepatocytes were detected within the portal areas. Quantitative analysis revealed limited engraftment of 0.79% to 2.95%, whereas control animals (sham OP) exhibited 4.16% (determined as relative activity of DPPIV when compared to wild-type liver). Repopulation was significantly enhanced (21.43%) when IR was performed prior to RTPI, optimum preconditioning settings being 90 min of ischemia and 1 h of reperfusion before transplantation. We demonstrate that RTPI alone is disadvantageous to donor cell engraftment, whereas the combination of IR with RTPI comprises an effective preparative regimen for liver repopulation. The method described clearly has potential for clinical application.