Endomyocardial biopsy is a valuable tool in cardiac diagnostics but is limited by low diagnostic yield and significant complication risks. Meanwhile, recent developments in transcriptomic and ...proteomic technologies promise a wealth of biological data from minimal tissue samples. To take advantage of the minimal tissue amount needed for molecular analyses, we have developed a sub-millimeter endovascular biopsy device, considerably smaller than current clinical equipment, and devised a low-input RNA-sequencing protocol for analyzing small tissue samples. In in vivo evaluation in swine, 81% of biopsy attempts (n = 157) were successful. High quality RNA-sequencing data was generated from 91% of the sequenced cardiac micro-biopsy samples (n = 32). Gene expression signatures of samples taken with the novel device were comparable with a conventional device. No major complications were detected either during procedures or during 7 days' follow-up, despite acquiring a relatively large number of biopsies (median 30) in each animal. In conclusion, the novel device coupled with RNA-sequencing provides a feasible method to obtain molecular data from the myocardium. The method is less traumatic and has a higher flexibility compared to conventional methods, enabling safer and more targeted sampling from different parts of the myocardium.
Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification ...and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.
OBJECTIVESThe aims of the present study were to describe the short-term rate of subjective memory worsening (SMW) and identify factors of importance for SMW in a large clinical sample treated for ...depression with electroconvulsive therapy (ECT).
METHODSThis register-based study included 1212 patients from the Swedish National Quality Register for ECT. Subjective memory worsening was defined as a 2-point worsening on the memory item of the Comprehensive Psychopathological Rating Scale from before to within 1 week after treatment. Associations between patient characteristics and treatment factors were examined using logistic regression.
RESULTSSubjective memory worsening was experienced in 26%. It was more common in women than in men (31% vs 18%; P < 0.001) and more common in patients aged 18 to 39 years than in patients 65 years or older (32% vs 22%; P = 0.008). Patients with less subjective memory disturbances before ECT had a greater risk of SMW. Patients in remission after ECT had a lower risk of SMW. A brief pulse width stimulus gave higher risk of SMW compared with ultrabrief pulse (odds ratio, 1.61; 95% confidence interval, 1.05–2.47).
CONCLUSIONSSubjective memory worsening is reported by a minority of patients. However, young women are at risk of experiencing SMW. Ultrabrief pulse width stimulus could be considered for patients treated with unilateral electrode placement who experience SMW. Each patient should be monitored with regard to symptoms and adverse effects, and treatment should be adjusted on an individual basis to maximize the clinical effect and with efforts to minimize the cognitive adverse effects.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Glioblastoma multiforme (GBM) is the most common and most severe form of malignant gliomas. The prognosis is poor with current combinations of pharmaceutical, radiotherapy, and surgical therapy. A ...continuous search for new treatments has therefore been ongoing for many years. Therapy with tumor-infiltrating lymphocytes (TILs) is a clinically promising strategy to treat various cancers, including GBM. An endovascular intraarterial injection of TILs as a method of delivery may, instead of intravenous infusion, result in better retention of effector cells within the tumor. Prior to clinical trials of intra-arterial injections with any cells, preclinical safety data with special emphasis on embolic–ischemic events are necessary to obtain. We used native rabbits as a model for intra-arterial injections with routine clinical catheter material and a clinical angiography suite. We selectively infused a total dose of 20 million activated T cells at a cell concentration of 4,000 cells/ml over 8 min of injection time. The rabbits were evaluated for ischemic lesions by 9.4 T magnetic resonance imaging (MRI) (n = 6), and for tracking of injected cells, single-photon emission computed tomography/computed tomography (SPECT/CT) was used (n = 2). In this study, we show that we can selectively infuse activated T cells to a CNS volume of 3.5 cm3 (estimated from the volumetric MRI) without catastrophic embolic– ischemic adverse events. We had one adverse event with a limited basal ganglia infarction, probably due to catheter-induced mechanical occlusion of one of the lateral lenticulostriatal arteries. The cells pass through the native brain without leaving SPECT signals. The cells then, over the first hours, end up in the liver to a large extent and to a lesser degree by the spleen, pancreas, and kidneys. Virtually no uptake could be detected in the lungs. This indicates a difference in biodistribution as opposed to other cell types when infused intravenously.
OBJECTIVESThe aim of this study was to compare the 0.5-millisecond pulse width with broader brief width stimulus and ultrabrief pulse width stimulus in respect to rates of subjective memory ...impairment and remission 6 months after completion of electroconvulsive therapy (ECT).
METHODSThis study used data from the Swedish National Quality Register for ECT. Inclusion criteria were bipolar or unipolar depression with or without psychosis, ECT with unilateral electrode placement, and data on the Montgomery-Åsberg Depression Rating Scale—Self-Assessment and the memory item of the Comprehensive Psychopathological Rating Scale (CPRS-M) before and 6 months after ECT. The primary outcomes were the distributions of patients with a maximum of 10 on the Montgomery-Åsberg Depression Rating Scale—Self-Assessment (remission) and a minimum of 2-step worsening in CPRS-M score according to the ECT pulse widths of <0.5, 0.5, and >0.5 millisecond.
RESULTThis study included 312 patients. The distributions of patients with remission or a minimum of 2-step worsening on the CPRS-M 6 months after completion of ECT showed no significant differences between the 3 pulse width groups. Older age was associated with a significantly higher rate of remission 6 months after ECT.
CONCLUSIONSIn this cohort of patients, no support was found for the previous research finding of lower rates of subjective memory disturbances 6 months after ultrabrief pulse width ECT in comparison with brief pulse width ECT. Older age was associated with higher remission rate 6 months after ECT. Large randomized studies are required to exclude the possibility of long-term differential effects between pulse widths.
Aim
The aim of the study was to test: (i) if D2/D3 binding in three functional subsections of striatum is different in patients with severe major depressive episodes than in controls; and (ii) if ...this difference is normalized after electroconvulsive therapy (ECT).
Methods
Nine inpatients were examined with positron emission tomography (PET) and the radioligand 11Craclopride before and after an average of 8.4 ECT sessions. Treatment response was assessed using the Montgomery–Åsberg Depression Rating Scale. Nine age‐ and sex‐matched controls were examined twice with PET and 11Craclopride.
Results
11Craclopride binding was significantly lower in all three subsections of striatum in patients compared to controls (Cohen's dz, 1.14–1.68; P = 0.003–0.027). Montgomery–Åsberg Depression Ratings decreased significantly after ECT (P < 0.001; Cohen's dz, 2.9). ECT had no statistically significant effect on 11Craclopride binding, although post‐ECT binding estimates were more similar to those obtained in controls in all subsections of striatum.
Conclusion
Using PET and 11Craclopride, we found support for the notion that severe major depressive episodes are associated with significantly lower dopamine D2/D3 binding in all three subsections of striatum compared to controls. We noted no significant effect on D2/D3 binding in the patient group after response to ECT.
There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and ...indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients.
A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire.
A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3.
Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Selective administration of mesenchymal stromal cells to the mesenteric arteries is a potential technique to overcome pulmonary trapping and increase the density of transplanted cells in extensive ...mural inflammation of the intestine, such as in inflammatory bowel disease and graft-versus-host disease. We injected 5 × 106 111In-oxine-labeled human decidual stromal cells (DSCs) to the rabbit superior mesenteric artery (SMA) using clinical routine catheters guided by an angiographical system under sterile conditions. We used longitudinal single-photon emission tomography at 6 h and at 1, 2, and 5 days to assess trafficking and distribution of DSCs. We used digital subtraction angiography, computed tomography, and hematoxylin and eosin stainings to determine biodistribution of cells and to assess safety end points. We found that selective injection of human DSCs to the rabbit SMA does not result in acute embolic complications. Furthermore, we found that IV administration resulted in extensive retention of the radiolabeled DSCs in the lungs, corroborating previous studies on pulmonary trapping. In sharp contrast, selective injections to the SMA resulted in uptake distributed in the intestine supplied by the SMA and in the liver, indicating that this approach could significantly increase the fraction of injected DSCs reaching the target tissue.
Does academic research affect local growth? Empirical evidence based on Swedish data. Regional Studies. The hypothesis that research activities do not merely affect the growth rate within the ...municipality hosting the university or university college but spill over to neighbouring municipalities is tested using data covering the Swedish municipalities between 1990 and 2010. Research activities are measured as the number of dissertations and the number of papers published in academic journals with peer-review system. The results suggest academic institutions by their presence and 'production' of human capital and new knowledge through research affect the regional growth pattern in both the municipality where the academic institution is located and the growth pattern of neighbouring municipalities.
In Ref. (GAMBIT Collaboration: Athron et. al., Eur. Phys. J. C. arXiv:1705.07908, 2017) we introduced the global-fitting framework GAMBIT. In this addendum, we describe a new minor version increment ...of this package. GAMBIT1.1 includes full support for Mathematica backends, which we describe in some detail here. As an example, we backend SUSYHD (Vega and Villadoro, JHEP 07:159, 2015), which calculates the mass of the Higgs boson in the MSSM from effective field theory. We also describe updated likelihoods in PrecisionBit and DarkBit, and updated decay data included in DecayBit.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK