Interprofessional education on complex patients in nursing homes: a focus group study.

BACKGROUND: An ageing population leads up to increasing multi-morbidity and polypharmacy. This demands a comprehensive and interprofessional approach in meeting patients' complex needs. This study describes graduate students' experiences of working practice based in interprofessional teams with complex patients' care needs in nursing homes. METHOD: Students from advanced geriatric nursing, clinical nutrition, dentistry, medicine and pharmacy at the University of Oslo in Norway were assigned to groups to examine and develop a care plan for a nursing home patient during a course. Focus groups were used, 21 graduate students participating in four groups. Data were collected during spring 2018, were inductively analysed according to a thematic analysis method (Systematic Text Condensation). An analytical framework of co-ordination practices was applied to get an in-depth understanding of the data. RESULTS: Three themes were identified: 1) Complex patients as learning opportunities- an eye-opener for future interprofessional collaboration 2) A cobweb of relations, and 3) Structural facilitators for new collective knowledge. Graduate university students experienced interprofessional education (IPE) on complex patients in nursing homes as a comprehensive learning arena. Overall, different co-ordination practices for work organization among the students were identified. CONCLUSIONS: IPE in nursing homes facilitated the students' scope from a fragmented approach of the patients towards a relational and collaborative practice that can improve patient care and strengthen understanding of IPE. The study also demonstrated the need for preparatory teamwork training to gain maximum benefit from the experience. Something that can be organized by the education institutions in the form of a stepwise learning module and as an online pre-training course in interprofessional teamwork. Further, focusing on the need for well thought through processes of the activity by the institutions and the timing the practice component in students' curricula. This could ensure that IPE is experienced more efficient by the students.

Donor Smoking and Older Age Increases Morbidity and Mortality After Lung Transplantation.

BACKGROUND: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free of chronic lung allograft dysfunction (CLAD) as morbidity variables. METHODS: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking status; these were further divided into three age groups: group A: 0 to 39 years; group B: 40 to 54 years; and group C: ≥55 years. RESULTS: One hundred fifty-one donors were former or actual smokers, 175 were nonsmokers, and 128 had unknown smoking histories. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from a smoking donor. CLAD-free survival was identical in all smoking groups, and overall survival was better both for lungs from nonsmoking donors and donors with unknown smoking status compared to lungs from smoking donors. One hundred sixty-nine donors were in age group A, 203 in B, and 82 in C. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from donors older than 55 years. Overall survival as well as CLAD-free survival was significantly lower with donors ≥55 years. CONCLUSIONS: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking waiting list mortality into account.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics.

Experimental pain impairs recognition memory irrespective of pain predictability.

BACKGROUND: Pain is hardwired to signal threat and tissue damage and therefore automatically attracts attention to initiate withdrawal or defensive behaviour. This well-known interruptive function of pain interferes with cognitive functioning and is modulated by bottom-up and top-down variables. Here, we applied predictable or unpredictable painful heat stimuli simultaneously to the presentation of neutral images to investigate (I) whether the predictability of pain modulated its effect on the encoding of images (episodic memory) and (II) whether subjects remember that certain images have been previously presented with pain (source memory). METHODS: Twenty-four healthy subjects performed a categorization task in which 80 images had to be categorized into living or non-living objects. We compared the processing and encoding of these images during cued and non-cued pain trials as well as cued and non-cued pain-free trials. Effects on recognition performance and source memory for pain were immediately tested using a surprise recognition task. RESULTS: Painful thermal stimulation impaired recognition accuracy (d', recollection, familiarity). This negative effect of pain was positively correlated with the individual expectation of pain interference and the attentional avoidance of pain-related words. However, the interruptive effect of pain was not modulated by the predictability of pain. Source memory for painful stimulation was at chance level, indicating that subjects did not explicitly remember that images had been paired with pain. CONCLUSIONS: Targeting negative expectations and a maladaptive attentional bias for pain-related material might help reducing frequently reported pain-induced cognitive impairments.

Generation and evaluation of a monoclonal antibody, designated MAdL, as a new specific marker for adenocarcinomas of the lung.

BACKGROUND: Different therapy regimens in non-small-cell lung cancer (NSCLC) are of rising clinical importance, and therefore a clear-cut subdifferentiation is mandatory. The common immunohistochemical markers available today are well applicable for subdifferentiation, but a fraction of indistinct cases still remains, demanding upgrades of the panel by new markers. METHODS: We report here the generation and evaluation of a new monoclonal antibody carrying the MAdL designation, which was raised against primary isolated human alveolar epithelial cells type 2. RESULTS: Upon screening, one clone (MAdL) was identified as a marker for alveolar epithelial cell type II, alveolar macrophages and adenocarcinomas of the lung. In a large-scale study, this antibody, with an optimised staining procedure for formalin-fixed tissues, was then evaluated together with the established markers thyroid transcription factor-1, surfactant protein-A, pro-surfactant protein-B and napsin A in a series of 362 lung cancer specimens. The MAdL displays a high specificity (>99%) for adenocarcinomas of the lung, together with a sensitivity of 76.5%, and is capable of delivering independent additional diagnostic information to the established markers. CONCLUSION: We conclude that MAdL is a new specific marker for adenocarcinomas of the lung, which helps to clarify subdifferentiation in a considerable portion of NSCLCs.

[Non-small-cell carcinoma of the lung with invasive Aspergillus infection after chemotherapy]. / Sepsis und Aspergillose bei einer Patientin mit nicht-kleinzelligem Lungenkarzinom.

HISTORY: A 56-year-old woman had two years previously undergone a neck dissection and subsequent adjuvant radiotherapy for an adenocarcinoma at the base of the tongue (pT2NOMOG2) when a percutaneous endoscopic gastrostomy (PEG) catheter had been placed. She was now admitted for chemotherapy, recent onset of severe pain in the left hip and knee having been caused by metastasis of a non-small-cell lung carcinoma (NSCLC). She was cachectic and in a reduced general condition (Karnofsky index 80), but had recently only occasionally used the PEG catheter. There were no inflammatory changes of the skin at the site of the PEG. TREATMENT, COURSE AND OUTCOME: The first chemotherapy cycle was initially without complication, but after a week the patient's general condition deteriorated and she developed nausea, fever and pain around the markedly inflamed site of the PEG catheter insertion. Laboratory tests indicated severe neutropenia. Intensive antibiotic and antimycotic treatment at first brought about some improvement, but she died 11 days after admission. Necropsy revealed invasive aspergillosis, with the PEG as the portal of entry and spreading to the stomach and intestines, where numerous hyphae were identified. There had also been a disseminated intravascular coagulopathy. CONCLUSION: Bacterial infections (and occasionally, but difficult to diagnose, fungal infection) are quite common as a result of neutropenia during chemotherapy of solid tumors. Various risk factors, including reduced general condition and weight loss, must be individually assessed in the prevention or treatment of associated infectious complications in such cases.

Tumors in the lung--morphologic features and the challenge of integrating biomarker signatures into diagnostics.

In the last decade, pathologic approaches concerning diagnosis and treatment of lung carcinomas have increasingly moved towards the implementation of molecular methods into the process of decision. In this study, an overview is given referring to the variety of tumors in the lung including common primary lung neoplasms and secondary tumors, and a modus operandi is presented which integrates immunology as well as molecular pathology within the process of finding correct diagnoses. Besides the conventional and approved methods and techniques leading to appropriate treatment including so-called targeted therapies, pathologist's work meanwhile depends on both histologic and molecular results. Since molecular techniques have increasingly entered the field of routine diagnostics, challenges and possibilities have changed and are still rapidly developing. The proceeding integration of molecular-biologic investigations into the process of diagnosing has changed the nature of diagnostics and will continuously grow in the near future. Only by obtaining a proper diagnosis, the optimal treatment of a patient can be assured, whereupon the knowledge of gene mutations and/or altered protein expression is crucial. By identifying those novel molecular target structures, the therapeutic spectrum is tremendously enlarged and will finally improve the patient's prognosis by personalized targeted therapies.

Expression analysis of EML4 in normal lung tissue and non-small cell lung cancer (NSCLC) in the absence and presence of chemotherapeutics.

Despite considerable progress in the development of individualized targeted therapies of tumor diseases, identification of additional reliable target molecules is still mandatory. One of the most recent targets is microtubule-associated human EML4 generating a fusion-type oncogene with ALK demonstrating marked transforming activity in lung cancer. Since EML4 is a poorly characterized protein with regard to expression, function and regulation in human tissue, specimens of human tumor and tumor-free tissues obtained from patients with NSCLC were analyzed to determine the cellular localization. All tissue samples have been previously fixed with the novel HOPE-technique and paraffin embedded. Determination of both gene expression and protein levels of EML4 were performed using RT-PCR, in situ hybridization as well as immunohistochemistry, respectively. In human NSCLC tissue samples, possible regulation of EML4 transcription upon chemotherapy with combinations of most established cytotoxic drugs for NSCLC treatment was also studied employing the recently established ex vivo tissue culture model STST. In normal lung, both marked mRNA and protein levels of EML4 were localized in alveolar macrophages. In contrast, lung tumor tissues always showed consistent transcriptional expression in situ and by RT-PCR. Stimulation of NSCLC tissues with chemotherapeutics revealed heterogeneous effects on EML4 mRNA levels. Based on its expression patterns in both tumor-free lung and NSCLC tissues, human EML4 is likely to be closely associated with processes involved in local inflammation of the lung as well as with tumor behavior. Thus, our results suggest that EML4 may have the potential as a therapeutic target molecule in NSCLC chemotherapy.

[Diagnostics for fungal infections of the lungs]. / Diagnostik von Pilzinfektionen der Lunge.

Recognition of and therapy for fungal infections of the lungs still presents problems even for the experienced clinician. The distinction between invasive mycoses of the lungs and fungal colonisations that do not require therapy is cinically difficult and can often not be made satisfactorily even with advanced microbiological diagnostics. One must differentiate between a primary, often locally limited, endemic pulmonary mycosis and a pulmonary mycosis against the background of a locally or systemically compromised immune system. Patients at risk include those with advanced HIV infections, patients under long-term antibiotic therapy as well as oncological and multimorbid patients. The pulmonary manifestation of a mycosis may not only be the starting point for a systemic dissemination but can also arise in the course of hematogenous spread of the infection. The latter can appear, for example, as an invasive pulmonary aspergillosis in immunesuppressed patients. Thus, early clinical, radiological and biological confirmation of the diagnosis is essential in order to avoid the possible complications of pulmonary mycosis.

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

BACKGROUND: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). METHODS: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). RESULTS: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). CONCLUSIONS: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

[Favorable response of pulmonary rheumatoid nodule to Rituximab]. / Gutes Ansprechen eines pulmonalen Rheumaknoten auf Rituximab.

Pulmonary rheumatoid nodules can be found in over 4% of patients with rheumatoid arthritis. Diagnostically they have to be differentiated from malignant and infectious processes. The present article describes a case of pulmonary rheumatoid nodule which responded well to Rituximab therapy.

Paniculitis mesentérica: infrecuente entidad clinicopatológica / Mesenteric panniculitis: a rare clinicopathological entity

Mesenteric panniculitis is an rare clinicopathological entity, presenting with a variety of manifestations, ranging from asymptomatic cases identified by image findings to retractile lesions that involve mesentery adjacent organs, such as bowel loops or encasement of the mesenteric vessels, producing ischemia and symptoms. A differential diagnosis should be established with other disorders, such as neoplasia, specially lymphoma when lymphnodesare present on the images. In general, it has a benign course, occasionally a biopsy sample is necessary to confirm the diagnosis. In symptomatic cases, improvement after use of steroids and immunomodulators has been observed. Surgery is an alternative treatment if a progressive course or a, lack of response to therapy are observed or when the diagnosis is uncertain.

La paniculitis mesentérica aparece como una entidad clinicopatológica infrecuente, con un abanico de manifestaciones, desde cuadros asintomáticos como hallazgos de estudio de imágenes, hasta lesiones retráctiles que comprometen órganos vecinos al mesenterio, como asas intestinales o engloban vasos mesentéricos produciendo isquemia y síntomas. Su presencia obliga a plantear el diagnóstico diferencial con otras entidades como los procesos neoplásicos entre ellos el linfoma, especialmente cuando se demuestran adenopatías en las imágenes. En general su evolución es benigna, en ocasiones es indispensable obtener biopsias para confirmar el diagnóstico. En casos sintomáticos el uso de corticoides e inmunomoduladores han sido de utilidad. La cirugía es una alternativa en casos de compromiso progresivo, falta de respuesta al tratamiento o duda diagnóstica.

Herida penetrante cardíaca / Cardiac penetrating wound

Las primeras descripciones de una lesión cardiaca se remontan al papiro de Edwin Smith alrededor del 3000 AC. Hasta el siglo IX, las heridas penetrantes cardiacas eran consideradas intratables y mortales. Fue en 1896, cuando se reportó la primera reparación cardiaca exitosa. Aunque la mortalidad ha disminuido con el paso del tiempo, una herida penetrante al corazón sigue teniendo un grave pronóstico y es causa importante de morbilidad y mortalidad en pacientes de trauma. En la actualidad, cada vez se ven con más frecuencia las heridas penetrantes cardiacas por arma de fuego, lo que indudablemente ensombrece aún más el pronóstico de estas lesiones, por lo que se torna de vital importancia para el cirujano que trabaja en una Unidad de Emergencia, conocer con exactitud los mecanismos fisiopatológicos que se ven involucrados en este tipo de situaciones, además de todas las complicaciones que pueden ocurrir al intentar reparar una herida penetrante cardiaca. Este artículo pretende dar una visión precisa, clara y actual del manejo de un paciente con una herida penetrante cardiaca.

The HOPE technique opens up a multitude of new possibilities in pathology.

Fixation of tissues with formalin results in well-preserved morphology but to a high degree leads to degradation of nucleic acids, which substantially constricts the spectrum of applicable molecular techniques. The novel HOPE-fixative with subsequent paraffin embedding, as an alternative to formalin, has been shown to result in a morphological preservation comparable to formalin-fixed, paraffin-embedded specimens. Due to a similar workflow like in formalin-fixation and paraffin embedding, the HOPE technique can be successfully established within any pathological institute. We have shown that DNA, RNA and proteins are protected in HOPE-fixed, paraffin-embedded tissues for at least eight years. Moreover, we described procedures which permit successful application of all common molecular techniques such as in situ hybridization targeting either DNA or RNA, immunohistochemistry without antigen retrieval and for formalin-refractory antigens, PCR, RT-PCR, Western blot, Northern blot, and transcription microarrays to HOPE-fixed, paraffin-embedded tissues. Furthermore, HOPE-fixed tissues can be used for the construction of tissue microarrays for enhanced high-throughput analyses on the molecular level. Using the HOPE technique as its crucial methodological base, ex vivo model systems could be established, e.g. for the simulation of early events in human infections and detection of chemotherapy resistances in human cancer. In addition to tissues, cell-culture preparations have been prepared utilizing the HOPE technique, which were then successfully applied to in situ hybridization targeting mRNA or immunocytochemistry with excellent preservation of morphological details. Taken together, the HOPE technique to date represents an alternative fixation that is, in contrary to other procedures, scientifically broadly analyzed. Therefore new possibilities are opened up especially within the rapidly growing field of molecular pathology.

[Automated quality control of ultrasonic B-mode scanners by applying an TMM 3D cyst phantom]. / Automatisierte Qualitätskontrolle von Ultraschall-B-Mode-Scanner in Kliniken und Praxen mithilfe von gewebeäquivalentem 3D-Zystenphantom.

Our goal was to apply an advanced and automated process to determine image quality of ultrasonic B-Mode scanner, quantitatively and precisely, with the help of a 3D artificial cylinder cyst phantom. (Artificial cysts are comparable to blood vessels). The detectability of cysts and lesions in defined sizes is an essential indicator of the imaging quality. A periodical test of the ultrasonic scanner in use is mandatory, because slowly-evolving defects of ultrasound probes can cause a continuous deterioration of imaging quality and lead to incorrect diagnosis which is falsely blamed on the apparatus.

Association study of Wegener granulomatosis and the functionally relevant A645G polymorphism in the bactericidal/permeability increasing protein (BPI) gene.

In antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV), bactericidal/permeability increasing protein (BPI) ANCAs are detected. Recent observations suggest that BPI-ANCAs can potentially contribute to a proinflammatory setting in the absence of proteinase 3 (PRTN3) ANCAs during the development of a pulmonary relapse by impeding the elimination of Gram-negative bacteria (GNB). However, it is as yet not clear whether the genetic background contributes to the generation of BPI-ANCAs in Wegener granulomatosis (WG) or if BPI polymorphisms are associated with WG. In this study we genotyped the functionally relevant single nucleotide polymorphism (SNP) A645 (Glu216Lys) of the BPI gene in 201 WG patients and 608 healthy controls. To investigate whether further SNPs might be associated with WG, we also examined an intragenic microsatellite marker. No significant differences were found between patients and controls. Thus BPI polymorphisms do not appear to contribute to genetic predisposition to WG. Moreover, our data do not suggest a genetic background for the generation of BPI-ANCAs in WG.

Stress-induced birefringence in large-mode-area micro-structured optical fibers.

We report on detailed numerical investigation of stress-induced birefringence in micro-structured solid-core optical fibers. The stress is induced either by external forces or stress applying parts inside the fiber. Both methods lead to different stress distributions where screening as well as enhancement effects due to the air-hole micro-structuring could be observed. Furthermore, we discuss the potential of the realization of polarization-maintaining low-nonlinearity micro-structured fibers that are suitable for applications in ultrafast optics.