Should We Reintroduce Previous Venous Thromboembolism Into Decision-Making for Anticoagulation in Atrial Fibrillation?

BackgroundWe aimed to investigate whether history of venous thromboembolism should be considered a prognostic factor for future thromboembolic events in patients with atrial fibrillation.MethodsThis was a nationwide cohort study of patients with incident atrial fibrillation from 2000-2017, defined and characterized using Danish health registries. Cox regression analyses were used to calculate hazard ratios and 95% confidence intervals for the outcomes ischemic stroke or systemic embolism, and ischemic stroke, systemic embolism, or venous thromboembolism, according to history of venous thromboembolism. Analyses were adjusted for components of the CHA₂DS₂-VASc score and time-varying use of oral anticoagulation.ResultsThe study included 246,313 patients with incident atrial fibrillation, of which 6,516 (2.6%) had previous venous thromboembolism. Patients with previous venous thromboembolism carried an overall similar adjusted risk of ischemic stroke or systemic embolism compared with patients without previous venous thromboembolism (reference; hazard ratio 0.99; 95% confidence interval, 0.90-1.09). When analyzing a composite thromboembolic outcome of ischemic stroke, systemic embolism, or venous thromboembolism, patients with previous venous thromboembolism were at high-risk (hazard ratio 1.76; 95% confidence interval, 1.64-1.90). Similar conclusions were drawn when stratifying by venous thromboembolism subtype, and when restricting to patients with low CHA₂DS₂-VASc scores or the non-anticoagulated subset of the study population.ConclusionPatients with atrial fibrillation and previous venous thromboembolism carried similar risk of ischemic stroke or systemic embolism compared with patients with atrial fibrillation without previous venous thromboembolism. Nonetheless, patients with previous venous thromboembolism remain a high-risk population due to an excess risk of future venous thromboembolism. Patients and physicians should keep this excess thromboembolic risk in mind when weighing the expected risks and benefits of oral anticoagulation in patients with atrial fibrillation.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

The Use and Intended Outcomes of Presence: A Focus Group Study

PURPOSE

To explore and understand the use and intended outcomes of presence from the perspective of and as experienced by nurses.

METHODS

Twenty‐seven nurses participated in one of four focus groups. Data were analyzed using Giorgi's phenomenological method.

FINDINGS

Four themes emerged: (1) therapeutic communication; (2) nurse well‐being; (3) dimensions of presence; and (4) intention to improve client outcomes.

CONCLUSIONS

Presence was described as a multidimensional intervention that required therapeutic communication and nurse well‐being with the intention of improving client outcomes. Study findings provide evidence of the significance of presence in the face of human interaction that is shifting to virtual, impersonal communication.     

Ein neuer Fall von schwerem Faktor XIII-Mangel

Zusammenfassung Bei einem SÄugling mit angeborenem homozygoten Faktor XIII-Mangel traten in den ersten Lebensmonaten eine schwere retroperitoneale und eine intracerebrale Blutung mit Ausbildung eines posthÄmorrhagischen Hydrocephalus auf. Mit der Transglutaminationsreaktion und dem Antiserum-Hemmtest war keine Faktor XIII-AktivitÄt me\bar. In der quantitativen Immunelektrophorese nach Laurell war die eigentlich wirksame Untereinheit A nicht nachweisbar, wÄhrend die Konzentration der Untereinheit S auf 47 % der Norm vermindert war. Nach Substitution mit 250 E. Faktor XIII-Konzentrat wurde enzymatisch eine Faktor XIII-AktivitÄt von 23 % gemessen. Die immunologisch bestimmte Konzentration der Untereinheit A entsprach dem Anstieg der Faktor XIII-AktivitÄt, die Konzentration der Untereinheit S nahm um 20 % zu. Im Alter von 8 Monaten wurde durch wiederholte Bestimmungen der Faktor XIII-AktivitÄt über einen Zeitraum von 39 Tagen nach Substitution der Turnover des Fibrinstabilisierenden Faktors durch eingehende Gerinnungsanalysen bestimmt. Die Halbwertszeit berechnete sich auf 4,7 Tage. Unter einer Dauersubstitutionstherapie mit 250 E. Faktor XIII im Abstand von 6 Wochen blieb das Kind blutungsfrei und entwickelte sich normal.     

Microbiology of parapharyngeal abscesses in adults: in search of the significant pathogens

European Journal of Clinical Microbiology & Infectious Diseases - We aimed to describe the microbiology of parapharyngeal abscess (PPA) and point out the likely pathogens using the following...     

Relationship Between Minor Myocardial Damage and Inflammatory Acute-Phase Reaction in Acute Coronary Syndromes

Background: In severe acute coronary syndromes (ACS) elevation of markers of inflammation and acute phase reaction (APR) like C-reactive protein (CRP) as well as a release of troponin have been reported.Using a high sensitivity troponin T (TnT) test we investigated whether an APR occurs in ACS only in the presence of ischemic myocardial damage. Methods: In 85 patients with ACS C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, thrombin antithrombin III complexes (TAT) and kallikrein were determined vs. high sensitive TnT (0.02 ng/ml) initially and 2 d later vs. 45 patients with stable angina pectoris and 42 controls. Results: In stable angina pectoris, markers of inflammation and coagulation were slightly elevated (p < 0.05). Initially in ACS elevations of CRP to 1.2 ± 0.3 mg/dl, SAA to 4.8 ± 2.6 mg/dl and fibrinogen to 448 ± 21 mg/dl (all p < 0.01 vs. controls) were found followed by a significant APR (p < 0.01).In the subgroup of TnT positive ACS patients, an APR with increased CRP (4.1 ± 1.3 mg/dl), SAA (20.4 ± 8.3 mg/dl), and fibrinogen (641 ± 45 mg/dl) was detectable (all p < 0.05 vs. TnT negative patients). In contrast, patients without TnT release showed APR markers comparable to patients with stable angina pectoris. Conclusion: Our findings demonstrate an association between myocardial injury in ACS and acute phase reaction as evidenced by several molecular markers. A highly sensitive TnT-test identified myocardial inury in about all patients with APR while a standard TnT cut-off (0.1 ng/ml) missed 32% of these patients. Thus, the APR in patients with ACS is strongly associated with at least minor ischemic myocardial damage and prior findings of an APR independent from myocardial injury are probably based on less sensitive troponin tests.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis [published erratum appears in Blood 1994 Aug 1;84(3):995]

Two B-cell lines, 2F7 and 10C9, were established by single cell cloning from biopsies obtained from two acquired immune deficiency syndrome patients with Burkitt's lymphoma. Representation of the original tumors was verified by demonstration of (1) identical biallelic rearrangement of Ig genes for 2F7 and (2) shared idiotype for 10C9. Both cell lines displayed cell-surface Ig and secreted Ig (IgM lambda for 2F7, IgM kappa for 10C9). IgMs from both cell lines immunoprecipitated actin; in addition, 2F7 IgM lambda immunoprecipitated recombinant human immunodeficiency virus type 1 (HIV-1) gp 160. 2F7 IgM lambda did not react with other autoantigens (double-stranded and single-stranded DNA, actin, bovine serum albumin, IgG), whereas 10C9 IgM kappa reacted with human IgG. The 2F7 IgM heavy-chain variable region (VH) showed a 95% nucleotide homology with a previously sequenced VHIII germline gene, hv3019b9, whereas the 10C9 IgM VH showed a 95% homology with a previously sequenced VHIV germline gene, VH4.21. Use of minimally modified VH genes and demonstration of reactivity with chronically present antigens (ie, actin, HIV-1 gp 160, or human IgG) suggests that B cells in HIV-1-infected individuals proliferating in response to chronic antigenic stimulation may be at increased risk for lymphomagenesis.     

Recombinant human GHRH(1-44)NH2: clinical utility and therapeutic development program

Growth hormone (GH) secretagogues are becoming increasingly attractive alternatives to GH or insulin-like growth factor-I (IGF-I) for the treatment of conditions that may benefit from activation of the GH/IGF-I axis. This stems from the realization that (1) GH secretagogues stimulate the pulsatile release of endogenous GH; (2) feedback control of endogenous GH and IGF-I is preserved, guarding against imbalances between GH and IGF-I levels; and (3) GH treatment is associated with adverse effects in the elderly. Of the GH secretagogues, growth hormone-releasing hormone (GHRH) remains the best characterized, in terms of identity of the ligand-receptor pair and its exclusive somatotropic activity at the level of the pituitary. Full-length natural GHRH (1-44) amide can now be produced by recombinant technologly on a commercially viable scale, and is currently being evaluated in early phase clinical trials. The purpose of these studies is to evaluate the efficacy and tolerability of chronic subcutaneous administration of GHRH over a range of doses in elderly subjects. Therapeutic areas that are being investigated in the elderly include congestive heart failure, osteoporosis, and improvements in body composition and function in the frail elderly.