Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes. METHODS: We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters. RESULTS: We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores. CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.     

Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria

A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone-usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by approximately 90% in laboratory and clinical E. coli strains. The structure of the pilicide bound to the P pilus chaperone PapD revealed that the pilicide bound to the surface of the chaperone known to interact with the usher, the outer-membrane assembly platform where pili are assembled. Point mutations in the pilicide-binding site dramatically reduced pilus formation but did not block the ability of PapD to bind subunits and mediate their folding. Surface plasmon resonance experiments confirmed that the pilicide interfered with the binding of chaperone-subunit complexes to the usher. These pilicides thus target key virulence factors in pathogenic bacteria and represent a promising proof of concept for developing drugs that function by targeting virulence factors.     

Prevalence and sensitivity of MET-criteria in a Scandinavian University Hospital

OBJECTIVE: To make a preliminary estimation of the workload for a medical emergency team (MET) in a Scandinavian University Hospital by recording prevalent physiological data on all adult patients and to see if the patients with deviating physiology (i.e. fulfilling the study criteria, in essence a set of simplified MET-criteria) had an elevated mortality. We also tested sensitivity and specificity by altering the cut-off levels of the calling criteria. DESIGN: Cross sectional prevalence study. SETTING: University hospital in the capital of Sweden. PATIENTS: Adult patients treated in the general wards of the hospital. Patients from psychiatric wards and intensive care units were excluded from the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 4.5% of the scored patients fulfilled the study criteria. These patients had a 30-day mortality of 25% (confidence interval 12.7-41.2) as compared to 3.5% (2.4-5) for the patients not fulfilling the study criteria. Extended criteria revealed 18 deaths within 30 days, 8 more deaths than the original study criteria. However, 123 patients - equalling 13.8% of the cohort (CI 11.6-16.2) - fulfilled these criteria as compared to the 40 patients fulfilling the original study criteria. Thus, the 30-day mortality of the patients with positive extended criteria totalled 14.6% (CI 8.9-22.1). Restricted criteria showed a mere 20 patients (2.2%; CI 1.4-3.5) and only 4 deaths, making 30-day mortality 20% (CI 5.7-43.7); thus, sensitivity was actually lower using restricted criteria. CONCLUSIONS: Even these modified - and simplified - MET-criteria proved to be able to single out patients with elevated mortality as compared to the rest of the hospital population. Extending the criteria significantly lowered sensitivity and would extend the MET-workload enormously. Restricting the criteria led to missed mortalities where intervention could be beneficial. The results suggest that a routine use of simple physiological tests can be of help in the identification of patients at risk.     

Review of organizational effects on the outcome of mental health treatments

Objective: As there are theoretical, clinical, and “common sense” reasons to expect a relationship between organizational factors and outcome in clinics providing psychotherapy and other mental health treatments, a review of empirical research in this area was undertaken with the aim of finding empirical evidence for organizational effects. Methods: A structured search for studies on organizational differences in patient mental health outcomes was performed using EBSCO host, Cochrane Library Database, and the Health Systems Evidence database at McMasters University. Finished studies published in English were included if they presented data from more than one mental health service and used change in symptom, level of functioning, or quality of life as outcome. Results: The search yielded not more than 19 studies fulfilling inclusion criteria. All studies showed some evidence for organization effects, and there was some evidence for organizational climate and culture explaining differences in outcome. Conclusion: Given that mental health treatments are likely to be especially susceptive to organizational effects, it is remarkable that not more research has been devoted to this. Clearly, more research is needed to study the consequences of work organization for the outcome of psychotherapy. Methodological issues in organizational studies are discussed.     

Alliance ruptures and repairs in psychotherapy in primary care

Objective: The association between alliance level and outcome in psychotherapy has been extensively studied. One way to expand this knowledge is to study alliance patterns. The main aims of this study were to examine how frequent alliance patterns with ruptures or rupture-repair episodes were in a naturalistic sample of psychotherapies in primary care, and if three alliance patterns (a Rupture pattern, a Repair pattern, and a No Rupture pattern) were differentially associated with treatment outcome. Method: The psychotherapies (N?=?605) included a wide range of different treatment orientations and patient diagnoses. Alliance patterns were studied at session-to-session level, using patient-rated alliance scores. Outcome data were analyzed using longitudinal multilevel modeling with a slopes-as-outcomes model. Results: The Repair pattern accounted for 14.7% (n?=?89) of the treatments, 10.7% (n?=?65) exhibited a Rupture pattern, and 74.5% (n?=?451) contained no ruptures. The Rupture pattern was associated with inferior treatment outcomes. The Repair pattern was, in longer treatments, associated with better outcomes than the No Rupture pattern. Conclusions: The results support theory about the importance of ruptures in the therapeutic alliance and suggest that identification of alliance ruptures is important in alliance-outcome research, for feedback purposes in clinical practice, and in training of therapists.     

Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

Background

The time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute Myocardial Perfusion Single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week.

Results

The time to reach 50% MI of the MaR (T₅₀) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T₅₀ when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 ± 23 min vs 310 ± 22 min, T₅₀ ± standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R² = 0.56, p < 0.001).

Conclusion

This is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.