Incidence and Risk Factors of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients Having Undergone Autologous Stem Cell Transplantation

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy. Due to their long survival and subsequently high cumulative doses of bisphosphonates, multiple myeloma patients have the highest risk of developing BRONJ of all patients treated with bisphosphonates. The purpose of the present study was to evaluate the incidence and risk factors for BRONJ in multiple myeloma patients after high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients and Methods: We retrospectively analyzed the data of 120 multiple myeloma patients after high-dose chemotherapy and ASCT treated with bisphosphonates and assessed the incidence and risk factors of BRONJ. Results: Of the 120 patients, 23 (19%) developed BRONJ. 6 patients suffered several BRONJ events, resulting in a total incidence of 23%. The risk for BRONJ was significantly higher for patients with rheumatism and recent dental manipulations. Furthermore, the number of previous bisphosphonate rotations, the duration of bisphosphonate therapy, and the type and cumulative dose of bisphosphonate used were associated with the incidence of BRONJ. Conclusion: Our study is the first to determine the risk of BRONJ in a homogeneous group of multiple myeloma patients treated with high-dose chemotherapy and ASCT

Complete devil's staircase and crystal--superfluid transitions in a dipolar XXZ spin chain: A trapped ion quantum simulation

Systems with long-range interactions show a variety of intriguing properties: they typically accommodate many meta-stable states, they can give rise to spontaneous formation of supersolids, and they can lead to counterintuitive thermodynamic behavior. However, the increased complexity that comes with long-range interactions strongly hinders theoretical studies. This makes a quantum simulator for long-range models highly desirable. Here, we show that a chain of trapped ions can be used to quantum simulate a one-dimensional model of hard-core bosons with dipolar off-site interaction and tunneling, equivalent to a dipolar XXZ spin-1/2 chain. We explore the rich phase diagram of this model in detail, employing perturbative mean-field theory, exact diagonalization, and quasiexact numerical techniques (density-matrix renormalization group and infinite time evolving block decimation). We find that the complete devil's staircase -- an infinite sequence of crystal states existing at vanishing tunneling -- spreads to a succession of lobes similar to the Mott-lobes found in Bose--Hubbard models. Investigating the melting of these crystal states at increased tunneling, we do not find (contrary to similar two-dimensional models) clear indications of supersolid behavior in the region around the melting transition. However, we find that inside the insulating lobes there are quasi-long range (algebraic) correlations, opposed to models with nearest-neighbor tunneling which show exponential decay of correlations

Brain connectivity alterations in early psychosis: from clinical to neuroimaging staging.

Early in the course of psychosis, alterations in brain connectivity accompany the emergence of psychiatric symptoms and cognitive impairments, including processing speed. The clinical-staging model is a refined form of diagnosis that places the patient along a continuum of illness conditions, which allows stage-specific interventions with the potential of improving patient care and outcome. This cross-sectional study investigates brain connectivity features that characterize the clinical stages following a first psychotic episode. Structural brain networks were derived from diffusion-weighted MRI for 71 early-psychosis patients and 76 healthy controls. Patients were classified into stage II (first-episode), IIIa (incomplete remission), IIIb (one relapse), and IIIc (two or more relapses), according to the course of the illness until the time of scanning. Brain connectivity measures and diffusion parameters (fractional anisotropy, apparent diffusion coefficient) were investigated using general linear models and sparse linear discriminant analysis (sLDA), studying distinct subgroups of patients who were at specific stages of early psychosis. We found that brain connectivity impairments were more severe in clinical stages following the first-psychosis episode (stages IIIa, IIIb, IIIc) than in first-episode psychosis (stage II) patients. These alterations were spatially diffuse but converged on a set of vulnerable regions, whose inter-connectivity selectively correlated with processing speed in patients and controls. The sLDA suggested that relapsing-remitting (stages IIIb, IIIc) and non-remitting (stage IIIa) patients are characterized by distinct dysconnectivity profiles. Our results indicate that neuroimaging markers of brain dysconnectivity in early psychosis may reflect the heterogeneity of the illness and provide a connectomics signature of the clinical-staging model

Aplastic Crisis as Primary Manifestation of Systemic Lupus Erythematosus

Aplastic crisis is an unusual feature of systemic lupus erythematosus (SLE). We report the case of a 54-year-old woman presenting with both (extravascular) Coombs-positive hemolytic anemia and laboratory findings of bone marrow hyporegeneration with concomitant severe neutropenia. A bone marrow biopsy confirmed aplastic crisis. Diagnostic work-up revealed soaring titers of autoantibodies (anti-nuclear, anti-double-stranded DNA, anti-cardiolipin-IgM, and anti-beta 2-glykoprotein-IgM antibodies), indicating a connective tissue disease as the most plausible reason for bone marrow insufficiency. As the criteria for SLE were fulfilled, we initiated an immunosuppressive therapy by steroids, which led to a rapid complete hematologic and clinical remission in our patient. In this case, we could report on one of the rare cases of SLE-induced aplastic crisis showing that this condition can be entirely reversed by immunosuppressive treatment and that SLE-induced aplastic crisis yields a good prognosis. In conclusion, in a case of aplastic crisis, physicians should be aware that SLE can be a rare cause that is accessible to specific treatment

Urban remediation : a new recovery-oriented strategy to manage urban stress after first-episode psychosis

Urban living is a major risk factor for psychosis. Considering worldwide increasing rates of urbanization, new approaches are needed to enhance patients' wellbeing in cities. Recent data suggest that once psychosis has emerged, patients struggle to adapt to urban milieu and that they lose access to city centers, which contributes to isolation and reduced social contacts. While it is acknowledged that there are promising initiatives to improve mental health in cities, concrete therapeutic strategies to help patients with psychosis to better handle urban stress are lacking. We believe that we should no longer wait to develop and test new therapeutic approaches. In this review, we first focus on the role of urban planning, policies, and design, and second on possible novel therapeutic strategies at the individual level. We review how patients with psychosis may experience stress in the urban environment. We then review and describe a set of possible strategies, which could be proposed to patients with the first-episode psychosis. We propose to group these strategies under the umbrella term of 'urban remediation' and discuss how this novel approach could help patients to recover from their first psychotic episode. The concepts developed in this paper are speculative and a lot of work remains to be done before it can be usefully proposed to patients. However, considering the high prevalence of social withdrawal and its detrimental impact on the recovery process, we strongly believe that researchers should invest this new domain to help patients regain access to city centers

Partial‐volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial-volume-based over probabilistic-based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex-matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel-wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub-region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect

Validierung und Reliabilitätsprüfung des Nijmegen Cochlear Implant Questionnaire in deutscher Sprache

Hintergrund: Der Nijmegen Cochlear Implant Questionnaire (NCIQ) ist ein krankheitsspezifischer Fragebogen zur Erhebung der gesundheitsbezogenen Lebensqualität von Patienten vor und nach Cochleaimplantation. Ziel der Arbeit: Validierung und Reliabilitätsprüfung der deutschen Übersetzung des NCIQ. Material und Methoden: Es wurde eine prospektive Studie an 100 postlingual ertaubten oder hochgradig schwerhörigen Patienten durchgeführt, welche präoperativ sowie 3 und 6 Monate nach einer Cochleaimplantation mittels NCIQ, Abbreviated Profile of Hearing Aid Benefit (APHAB) und Hearing Participation Scale (HPS) untersucht wurden. Als Kontrolle fungierte ein postlingual ertaubtes oder hochgradig schwerhöriges, unbehandeltes Patientenkollektiv (n = 54). Cronbach‑α und Test-Retest-Reliabilität dienten der Reliabilitätsüberprüfung. Es wurde auf Inhalts‑, Übereinstimmungs- und auf diskriminative Validität getestet. Die Konstruktvaliditätsprüfung basiert auf kürzlich veröffentlichen Daten. Als Gütekriterien wurden die Sensitivität und eine ROC("Receiver Operating Characteristic")-Analyse, inklusive AUC("Area Under the ROC Curve")-Betrachtung, eingesetzt. Ergebnisse: Das Test-Retesting ergab nach 3 und 6 Monaten postoperativ stabile NCIQ-Werte. Die Cronbach-α-Werte wiesen auf eine gute interne Konsistenz hin. Der NCIQ diskriminierte valide zwischen behandelten und unbehandelten Patientengruppen. Es ergaben sich statistisch signifikante, wenn auch schwache, Korrelationen zwischen dem NCIQ und dem APHAB (r = -0,22; p = 0,04) und dem HPS (r = 0,30; p = 0,01). Sensitivitäts- und ROC-Analysen zeigten eine gute Messqualität des deutschsprachigen NCIQ. Schlussfolgerung: Die deutsche Übersetzung des NCIQ misst zuverlässig und valide die Lebensqualität vor und nach Cochleaimplantation und kann zur klinischen Erfolgskontrolle nach Cochleaimplantationen verwendet werden.Background: The Nijmegen Cochlear Implant Questionnaire (NCIQ) is a disease-specific questionnaire to determine the health-related quality of life (HRQoL) of patients before and after cochlear implantation. Objective: This study aimed to assess the validity and reliability of the German translation of the NCIQ. Materials and methods: A prospective study was performed in 100 postlingually deaf or severely hearing-impaired patients. HRQoL was assessed using the NCIQ, the Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Hearing Participation Scale (HPS) before as well as 3 and 6 months after cochlear implantation. An untreated group of postlingually deaf or severely hearing-impaired patients (n = 54) served as a control. Cronbach's α and test–retest reliability were measured. The content, discrimination, and agreement validity were tested. The evaluation of construct validity was based on recently published data. Sensitivity and receiver operating curve (ROC) analysis, including consideration of the area under the curve (AUC), were used as quality criteria. Results: The test-retest analysis showed stable NCIQ values 3 and 6 months postoperatively. The Cronbach’s α values indicated good internal consistency. The NCIQ validly discriminated between treated and untreated patient groups. There were statistically significant albeit weak correlations between the NCIQ and the APHAB (r = -0.22; p = 0.04) and the HPS (r = 0.30; p = 0.01). Sensitivity and ROC analyses showed good measurement quality of the German-speaking NCIQ. Conclusion: The German translation of the NCIQ reliably and validly measures HRQoL before and after cochlear implantation and can be used for clinical monitoring after treatment with cochlear implants

N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial

Mechanism-based treatments for schizophrenia are needed, and increasing evidence suggests that oxidative stress may be a target. Previous research has shown that N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor almost devoid of side effects, improved negative symptoms, decreased the side effects of antipsychotics, and improved mismatch negativity and local neural synchronization in chronic schizophrenia. In a recent double-blind randomized placebo-controlled trial by Conus et al., early psychosis patients received NAC add-on therapy (2700 mg/day) for 6 months. Compared with placebo-treated controls, NAC patients showed significant improvements in neurocognition (processing speed) and a reduction of positive symptoms among patients with high peripheral oxidative status. NAC also led to a 23% increase in GSH levels in the medial prefrontal cortex (GSHmPFC) as measured by (1)H magnetic resonance spectroscopy. A subgroup of the patients in this study were also scanned with multimodal MR imaging (spectroscopy, diffusion, and structural) at baseline (prior to NAC/placebo) and after 6 months of add-on treatment. Based on prior translational research, we hypothesized that NAC would protect white matter integrity in the fornix. A group x time interaction indicated a difference in the 6-month evolution of white matter integrity (as measured by generalized fractional anisotropy, gFA) in favor of the NAC group, which showed an 11% increase. The increase in gFA correlated with an increase in GSHmPFC over the same 6-month period. In this secondary study, we suggest that NAC add-on treatment may be a safe and effective way to protect white matter integrity in early psychosis patients

Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex

Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial