Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV Cohort Study

BACKGROUND: We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996. METHODS: From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007). RESULTS: The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P = .007) but similar CD4+ T cell counts (60 vs. 71 cells/microL; P = .25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P < .001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/microL, 0.52; 95% CI, 0.32-0.85; P = .010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P = .006). CONCLUSIONS: cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependent on cART use and baseline CD4+ T cell count.

JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.

"Fact versus Fiction – How paratextual information shapes our reading processes"

Our life is full of stories: some of them depict real-life events and were reported, e.g. in the daily news or in autobiographies, whereas other stories, as often presented to us in movies and novels, are fictional. However, we have only little insights in the neurocognitive processes underlying the reading of factual as compared to fictional contents. We investigated the neurocognitive effects of reading short narratives, labeled to be either factual or fictional. Reading in a factual mode engaged an activation pattern suggesting an action-based reconstruction of the events depicted in a story. This process seems to be past-oriented and leads to shorter reaction times at the behavioral level. In contrast, the brain activation patterns corresponding to reading fiction seem to reflect a constructive simulation of what might have happened. This is in line with studies on imagination of possible past or future events.

Desmoplastic small round cell tumor: A rare cause of a progressive brachial plexopathy.

Introduction: Desmoplastic small round cell tumor (DSRCT) is an uncommon, embryonic-type neoplasm, typically presenting as an abdominal mass in young men. A single case of DSRCT arising in the peripheral nervous system has been reported. Methods: The clinical course, imaging, electrophysiological, intraoperative, histopathological, molecular findings, and postoperative follow-up are reported. Results: A 43-year-old man presented with slowly progressive right brachial plexopathy. Magnetic resonance imaging revealed an enlarged medial cord with heterogeneous contrast enhancement. Histology showed a "small round cell" neoplasm with a polyphenotypic immunoprofile, including epithelial and mesenchymal markers. A pathognomonic fusion of Ewing sarcoma breakpoint region 1 and Wilms tumor 1 genes (EWSR1/WT1) was present. Treatment involved gross total excision and local radiotherapy. Conclusion: Our findings confirm the occurrence of DSRCT as a primary peripheral nerve tumor. Despite its usually very aggressive clinical course, prolonged recurrence-free survival may be reached. Histomorphology and immunoprofile of DSRCT may lead to misdiagnosis as small cell carcinoma. © 2013 Wiley Periodicals, Inc.

Science & Fiction: Imagination und Realität des Weltraums

Der Kosmos ist seit Menschengedenken ein Gegenstand der forschenden Neugierde und der phantastischen Projektion. Wissenschaft und Kunst, science and fiction, Realität und Fiktion, sind sich nie so nah wie angesichts des Weltraums, jenes unerreichbaren Ganzen. Astronom / innen und Weltraumingenieur/innen beschäftigen space artists, und umgekehrt schöpfen Schriftsteller/innen und Filmemacher/innen aus den Entdeckungen der Physik und Weltraumtechnik. Der Leitgedanke der diesem Band zugrunde liegenden Ringvorlesung Science & ­Fiction: Imagination und Realität des Weltraums war, die Weltraumexploration im weitesten Sinne kulturgeschichtlich zu verstehen, um alle Wissenschaften in das Thema einzubeziehen. Es wurden daher sowohl Naturwissenschaftler/innen als auch ebenso viele Geisteswissenschaftler/innen eingeladen. Sie beleuchten in ihren Beiträgen die Geschichte der wissenschaftlichen, technischen und künstlerischen Visualisierungen des Weltraums und stellen Ergebnisse und Projekte der Weltraumforschung vor. Ein besonderes Interesse liegt dabei auf den vielfältigen Beziehungen zwischen den Bereichen der fiction – der Visualisierungen und Imaginationen des Weltraums – und der science – der Realitäten der naturwissenschaftlichen Erforschung des Weltraums.

Systemic light-chain amyloidosis revealed by progressive nail involvement, diffuse alopecia and sicca syndrome: report of an unusual case with a review of the literature.

Immunoglobulin light-chain (AL) amyloidosis is a form of systemic amyloidosis in which the fibrils are derived from monoclonal light chains. We report a case of a 66-year-old woman presenting with nail changes, parchment-like hand changes, progressive alopecia and sicca syndrome. Histopathological studies of biopsy specimens of the scalp, the nail, minor labial salivary glands and abdominal skin revealed deposits of AL κ-type amyloid. Urine protein electrophoresis exhibited a weak band of κ-type light chains. Based on this striking case, we here review the characteristic nail and hair manifestations associated with systemic amyloidosis. Knowledge of these signs is important for an early diagnosis of systemic amyloidosis, identification of the underlying disease and patient management.

Melodrama and Narrative Fiction: Towards a Typology

Recent research on melodrama has stressed its versatility and ubiquity by approaching it as a mode of expression rather than a theatrical genre. A variety of contexts in which melodrama is at work have been explored, but only little scholarly attention has been paid to the relationship between melodrama and novels, short stories and novellas. This article proposes a typology of melodrama in narrative prose fiction, examining four different categories: Melodrama and Sentimentalism, Depiction of Melodramatic Performances in Narrative Prose Fiction, Theatrical Antics and Aesthetics in Narrative Prose Fiction and Meta-Melodrama. Its aim is to clarify the ways in which melodrama, ever since its early days on the stages of late eighteenth-century Europe, has interacted with fictional prose narratives, thereby shaping the literary imagination in the Anglophone world.