Suspicion and treatment of severe sepsis. An overview of the prehospital chain of care

Sepsis is a life-threatening condition where the risk of death has been reported to be even higher than that associated with the major complications of atherosclerosis, i.e. myocardial infarction and stroke. In all three conditions, early treatment could limit organ dysfunction and thereby improve the prognosis

p53 is associated with high-risk and pinpointsTP53missense mutations in mantle cell lymphoma

Survival for patients diagnosed with mantle cell lymphoma (MCL) has improved drastically in recent years. However, patients carrying mutations in tumour protein p53 (TP53) do not benefit from modern chemotherapy-based treatments and have poor prognosis. Thus, there is a clinical need to identify missense mutations through routine analysis to enable patient stratification. Sequencing is not widely implemented in clinical practice for MCL, and immunohistochemistry (IHC) is a feasible alternative to identify high-risk patients. The aim of the present study was to investigate the accuracy of p53 as a tool to identify patients withTP53missense mutations and the prognostic impact of overexpression and mutations in a Swedish population-based cohort. In total, 317 cases were investigated using IHC and 255 cases were sequenced, enabling analysis of p53 andTP53status among 137 cases divided over the two-cohort investigated. The accuracy of predicting missense mutations from protein expression was 82%, with sensitivity at 82% and specificity at 100% in paired samples. We further show the impact of p53 expression andTP53mutations on survival (hazard ratio of 3 center dot 1 in univariate analysis for both), and the association to risk factors, such as high MCL International Prognostic Index, blastoid morphology and proliferation, in a population-based setting.Peer reviewe

B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1*07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA’-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL

Rationale for a Swedish cohort consortium

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.Peer reviewe

miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator

Recent studies show that mantle cell lymphoma (MCL) express aberrant miRNA profiles, however, the clinical effect of miRNA expression has not previously been examined and validated in prospective, large, homogenously treated cohorts. We analyzed diagnostic MCL samples from the Nordic MCL2 and MCL3 clinical trials, in which all patients had received Rituximab-high-dose cytarabin alternating with Rituximab-maxiCHOP, followed by BEAM and autologous stem cell support. We performed genome-wide miRNA microarray profiling of 74 diagnostic MCL samples from the MCL2 trial (screening cohort). Differentially expressed miRNAs were re-analyzed by qRT-PCR. Prognostic miRNAs were validated by qRT-PCR in diagnostic MCL samples from 94 patients of the independent MCL3 trial (validation cohort). Three miRNAs (miR-18b, miR-92a, miR-378d) were significantly differentially expressed in patients who died from MCL in both the screening- and the validation cohort. MiR-18b was superior to miR-92a and miR-378d in predicting high risk. Thus, we generated a new MIPI-B-miR prognosticator, combining expression-levels of miR-18b with MIPI-B data. This prognosticator improved identification of high risk patients compared to MIPI-B with regard to cause-specific survival (P=0.015), overall survival (P=0.006) and progression-free survival (P<0.001). Transfection of two MCL cell lines with miR-18b decreased their proliferation rate without inducing apoptosis, suggesting miR-18b may render MCL cells resistant to chemotherapy by decelerating cell proliferation. Thus, we conclude that overexpression of miR-18b identifies patients with poor prognosis in two large prospective MCL cohorts and adds prognostic information to MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance

DNA repair genes are selectively mutated in diffuse large B cell lymphomas

DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis

Оценка эффективности комплекса методов медицинской реабилитации пациентов с двигательной дисфункцией кисти вследствие острых нарушений мозгового кровообращения

МЕДИЦИНСКАЯ РЕАБИЛИТАЦИЯКИСТЬ РУКИКИСТЬПСИХОМОТОРНАЯ АКТИВНОСТЬДВИГАТЕЛЬНЫХ НАВЫКОВ РАССТРОЙСТВА /РЕАБИЛРЕАБИЛИТАЦИЯ /МЕТОДЫМОЗГОВОГО КРОВООБРАЩЕНИЯ РАССТРОЙСТВА /ОСЛ /РЕАБИЛЛЕЧЕБНАЯ ГИМНАСТИКАМЕЛКАЯ МОТОРИКАЦелью исследования являлось изучение эффективности комплекса медицинской реабилитации, разработанного на основе зеркальной визуальной обратной связи, элементов двигательной терапии индуцированным ограничением, метода тренировки двигательных навыков кисти с использованием латексных резинок и авторского метода тренировки мелких моторных навыков у пациентов с двигательной дисфункцией кисти вследствие острого нарушения мозгового кровообращения различной степени выраженности. В исследовании приняли участие 62 пациента, разделенные на 2 группы сравнения, сопоставимые по полу, возрасту, реабилитационному периоду и потенциалу. Для анализа результатов использовались методы оценки эффективности медицинской реабилитации пациентов с двигательной дисфункцией кисти, утвержденные министерством здравоохранения Республики Беларусь. По результатам исследования было выявлено межгрупповое различие в восстановлении мелкой моторики, показателей кистевой динамометрии, уровне самооценки пациентом утраты функции верхней конечности, степени выраженности тревожной и депрессивной симптоматики, проявляющееся в более качественном результате у пациентов клинической группы. Также выявлено преобладание увеличений показателей и при оценке качества жизни у респондентов, проходящих предложенный комплекс методов медицинской реабилитации над пациентами контрольной группы. Разработанный комплекс, в условиях применения в соответствии с алгоритмом, позволяет более качественно по сравнению с пациентами, проходящими стандартный курс медицинской реабилитации, восстановить двигательный навык, утраченный вследствие острого нарушения мозгового кровообращения, улучшить степень самообслуживания, качества жизни и приводит к снижению выраженности тревожно-депрессивной симптоматики.Objectives. To study the efficacy of the medical rehabilitation complex developed on the basis of mirror visual feedback, elements of constraint induced movement therapy, the method of hand motor skills’ training with the use of latex rubber bands and the author’s own method of fine motor skills training in patients with motor dysfunction of the hand caused by acute cerebral circulation of different severity degree. Material and methods. The study involved 62 patients, divided into 2 comparison groups, matched by sex, age, rehabilitation period, and potential. To analyze the results we used methods for assessing the effectiveness of medical rehabilitation of patients with motor dysfunction of the hand, which were approved by the Ministry of Health of the Republic of Belarus. Results. The study revealed an intergroup difference in restoring fine motor skills, hand dynamometry indices, the patient’s self-assessment of the upper limb function loss, the severity of anxiety and depression symptoms, which manifests itself in a better result in patients of the clinical group. The prevalence of the increased indicators was also revealed when assessing the life quality of respondents undergoing the proposed complex of medical rehabilitation methods over patients of the control group. Conclusions. The developed complex, in terms of application in accordance with the algorithm, allows more qualitatively compared with patients undergoing a standard course of medical rehabilitation, to restore the motor skill lost because of acute cerebral circulation disturbance, to improve the degree of self-care, quality of life and leads to a decrease in anxiety-depression symptoms

Supply Chain Management, Just-In-Time och inköp i ett fusionsperspektiv : En fallstudie på Colorama AB

Så länge som människor strövat omkring på jorden har det bytts och handlats med varor och tjänster. Det är i människans natur att göra affärer. Logistik och inköp har därför naturligt blivit stycken i den mänskliga handelshistorien, samhället men främst företag påverkas och påverkar denna nutidshistorias utveckling. Då konkurrens har blivit ett stort inslag för att lyckas i ett företag så har företag försökt hitta nya metoder för att hävda sig på den globaliseringen marknaden. De verktygen kan skilja sig från företag till företag beroende av vilka lösningar företag vill lösa men exempel på det kan vara Supply Chain Management som kommer att behandlas i denna uppsats. De andra teorier som kommer beröras är fusion, Just-in-Time och inköp. Dessa kommer att utifrån ämnet att appliceras på studieobjektet så att skillnader framkommer. Fallstudien som uppsatsen baseras på färgkedjan Colorama AB, där intervjun skedde med butiksägaren och ledamoten i styrelsen, Patrik Graff. För att även få en extern synvinkel på temat som denna uppsats behandlar har även en intervju med en seniorkonsult på managementföretaget Establish gjorts. Detta för att kunna se dessa två vinklar mor teorin och därefter kunna dra en slutsats. Syftet var att undersöka om Colorama efter sammanslagningen börjat styra sina leverantörer mer än innan men även se om de har ändrat i sitt logistiska tänkande då kedjan blev mycket större än den var innan sammanslagningen. När teorin jämförs med empirin framkommer ett klart samband att studieobjektet ligger närmare det klassiska synsättet när det gäller inköp av varor och relationer gentemot leverantörer. Colorama är i utvecklingsfasen då de endast funnits sedan i början av 2007 och mycket kan hända men det som har analyserats utav intervjun är att de kommer allt längre från sina leverantörer.As long as humans have roamed the Earth, goods and services have been traded. It is in our nature to do business. Logistics and purchase have thanks to those facts become a part of the human trading history, its society but rather companies that have to changes to keep up with the changes of this era. But it’s also those companies and societies that alter this history era due to their business decisions and decisions to adept theories. Due to competitions companies have to come across new methods to struggle better on their globalized market. The method that are needed are different in all companies, one tool that can be adapted is Supply Chain Management. Other theories that will be mentioned in this essay are Just-In-Time, fusion and purchase. These theories will work as a map how to rule a modern company in aspects of logistics and purchase, our map will be applied on Colorama AB to see the differences between a reality and theory. To get a better grip of how reality looks like beside our case study, an interview was done with a senior consult of a management company that work with logistics. The main purpose of this essay was to examine if Colorama, after the fusion, have started to organize their deliverers more and if they had change their logistic thinking due to the new company size. The examination showed that Coloramas point of view were quite different from theory contains and Establish point of view, Colorama would rather be classified as a user of the classic theories rather than the ones mention above. Colorama are still a young company in their development phase and much will happened over time, but analyses shows that they drifting apart from their supplier

Patients with autoimmune diseases have an altered activity of the PD-1 pathway and proportions of Epstein-Barr virus infected cells in benign lymphadenopathies

Patients with autoimmune diseases (AD) have an increased risk to develop benign lymphadenopathies compared to patients without AD. The aim with this study was to determine the role of the PD-1 pathway and the number of cells harboring Epstein-Barr virus (EBV) in benign lymphadenopathies in patients with AD (cases) compared to patients without AD (controls). Pathology registries were screened to identify patients with biopsies diagnosed as benign lymphadenopathy and medical journals were reviewed for information on AD. Immunohistochemical stainings (PD-1 and PD-L1) and EBER in situ hybridization for EBV were applied on lymph node biopsies in patients with AD (n = 22) and patients without AD (n = 57). The case group was compared with the control group with Wilcoxon-signed rank, chi-square and Fischers exact test. There was a statistically significantly higher proportion of PD-1+ cells and a tendency for a lower prevalence of PD-L1+ and EBV+ cells in cases compared to controls. Apparently, patients with AD have an altered immune response as revealed in benign lymphadenopathies compared to patients without AD. If this association might be a piece of the puzzle for the increased risk of development of lymphomas in patients with AD remains to be determined