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Few patients scattered among centers complicate investigation of thrombotic thrombocytopenic purpura (TTP) and Evans syndrome (ES). Routinely collected Danish register data captures the total population and includes lifelong follow-up. We aimed to validate registered TTP and ES diagnoses and to explore clinical characteristics. We identified all patients in Denmark with diagnosis registrations indicative of TTP or ES in the Danish National Patient Registry 2000-2019, validated diagnoses through medical record review, and extracted and presented data on initial treatment and complications. Diagnoses for patients registered with TTP and ES were confirmed for 46% and 59%, respectively. Among validated TTP patients the most widespread complications at time of diagnosis were neurological symptoms or deficits, observed in 81% of cases. Other frequent types of complications in TTP patients were any organ failure (32%) and infection (25%). Initial management and complications did not change for patients diagnosed between 2000 and 2009 and 2010 and 2019, and survival remained constant (overall mortality 26%, median follow up of 8.4 years). Treatments and complications also remained unchanged for ES patients. Overall, diagnostic accuracy, complications and prognosis have remained relatively constant for patients over the study period. These now validated cohorts of Danish TTP and ES patients will be utilized in future studies to examine long-term health outcomes.

The nephrotoxic potential of aminoglycosides is primarily correlated to the duration of therapy. However, there are discrepancies between previous studies regarding the effect of short course treatment. The aim of this study was to compare renal function, renal recovery and mortality in a large cohort of patients with bacteraemia, who were empirically treated with regimens with and without a short course (≤ 3 days) of once daily dosing of gentamicin. This was a retrospective propensity score-matched cohort study based on all patients with bacteraemia in a Danish hospital in the period 2010–2013. We included 702 patients who received gentamicin, and 702 who did not receive gentamicin. To determine the impact of gentamicin on renal function, we used a modified version of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for acute kidney injury (AKI), and the resulting data were analyzed by logistic regression. We used Cox regression analysis to compare the adjusted mortality rates between the two groups. According to the KDIGO criteria, we found no significant difference in the occurrence of AKI between the two groups (odds ratio (OR) 0.90 (95% CI 0.68–1.20)). We found that recovery of renal function was similar in the two groups, OR 1.00 (95% CI 0.63–1.60). The hazard ratio for 90-day all-cause mortality was 1.02 (95% CI 0.84–1.25). Short-course empirical gentamicin treatment of patients with bacteraemia was not associated with an increased incidence of AKI nor all-cause mortality in this study, and we observed similar reversibility of renal function.

Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in the era of positron emission tomography (PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT.

Ant supercolonies (large networks of interconnected nests) represent the most extreme form of multi-queen breeding (polygyny) and have been found across ant lineages, usually in specific long-term stable populations. Many studies on the genetic population structure and demography of ant supercolonies have been done in recent decades, but they have lacked multicolonial control patches with separated colonies headed by a single or few queens so the origin of the supercolonial trait syndrome has remained enigmatic. Here, we set out to compare sympatric supercolonial and multicolonial patches in two natural Danish populations of the common red ant Myrmica rubra. We used DNA microsatellites to reconstruct genetic colony/population structure and obtained morphological and density measurements to estimate life history and ecology covariates. We found that supercolonies in both populations completely dominated their patches whereas colonies in multicolonial patches coexisted with other ant species. Supercolony patches had very low genetic differentiation between nests, negligible relatedness within nests, and lower inbreeding than multicolonial patches, but there were no significant morphological differences. One population also had nests that approached true outbred monogyny with larger workers and males but smaller queens than in the two other social nest types. Our results suggest that once smaller colonies start to adopt additional queens, they also gain the potential to ultimately become supercolonial when the habitat allows rapid expansion through nest budding. This is relevant for understanding obligate polygyny in ants and for appreciating how and why introduced North American populations of M. rubra have recently become invasive.

Cannabinoids reduce tremor associated with motor disorders induced by injuries and neurodegenerative disease. Here we show that this effect is mediated by cannabinoid receptors on astrocytes in the ventral horn of the spinal cord, where alternating limb movements are initiated. We first demonstrate that tremor is reduced in a mouse model of essential tremor after intrathecal injection of the cannabinoid analog WIN55,212-2. We investigate the underlying mechanism using electrophysiological recordings in spinal cord slices and show that endocannabinoids released from depolarized interneurons activate astrocytic cannabinoid receptors, causing an increase in intracellular Ca 2+ , subsequent release of purines and inhibition of excitatory neurotransmission. Finally, we show that the anti-tremor action of WIN55,212-2 in the spinal cords of mice is suppressed after knocking out CB 1 receptors in astrocytes. Our data suggest that cannabinoids reduce tremor via their action on spinal astrocytes. Astrocytes regulate synaptic transmission. Carlsen et al. report that spinal astrocytes activated by endocannabinoids inhibit excitatory synaptic transmission and, thereby, decrease tremor.

The aim of the study was to evaluate the ability to detect extra-cardiac foci by means of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with definite endocarditis (IE) according to the modified Duke criteria and investigate the clinical impact of the findings. From January 2011 to December 2015 we included 178 patients (mean age 66 ± 14 years, 25% female) with IE in this multicentre study. FDG-PET/CT was part of the work-up for extra-cardiac foci in the including hospitals and was performed at a median of 9 days (IQR 10) after IE was diagnosed. In 114 patients FDG-PET/CT identified 166 lesions: 52 (31%) infectious lesions, 21 (13%) cases of cancer, 7 (4%) cases of embolism, 60 (36%) reactive findings, and 26 (16%) other types of lesions. A total of 74 new extra-cardiac findings, not previously discovered by other modalities, were identified in 62 patients and resulted in additional investigations in 29 patients and a change in treatment in 18 patients (10%). The most frequent diagnoses discovered by FDG-PET/CT were colon polyps, cancer, and spondylodiscitis. There was a higher rate of findings leading to a change in treatment in patients above 67 years of age infected with other bacterial aetiologies than streptococci. FDG-PET/CT was useful to detect extra-cardiac foci. FDG-PET/CT findings may lead to unnecessary investigations. One out of 10 the patients with definite endocarditis had underwent a change in treatment regimen based on the FDG-PET/CT findings.

Abstract Rationale The tobacco harm reduction literature is replete with vague language, far-reaching claims, and unwarranted certainty. The American Thoracic Society has increasingly recognized the need for a framework for reliably making such claims. Evidence-based standards improving the scientific value and transparency of harm reduction claims are expected to improve their trustworthiness, clarity, and consistency. Methods Experts from relevant American Thoracic Society committees identified key topic areas for discussion. Literature search strategy included English language articles across Medline, Google Scholar, and the Cochrane Collaborative databases, with expanded search terms including tobacco, addiction, smoking, cigarettes, nicotine, and harm reduction. Workgroup members synthesized their evidentiary summaries into a list of candidate topics suitable for inclusion in the final report. Breakout groups developed detailed content maps of each topic area, including points to be considered for suggested recommendations. Successive draft recommendations were modified using an iterative consensus process until unanimous approval was achieved. Patient representatives ensured the document’s relevance to the lay public. Results Fifteen recommendations were identified, organized into four framework elements dealing with: estimating harm reduction among individuals, making claims on the basis of population impact, appropriately careful use of language, and ethical considerations in harm reduction. Discussion This statement clarifies important principles guiding valid direct and inferential harm reduction claims. Ideals for effective communication with the lay public and attention to unique ethical concerns are also delineated. The authors call for formal systems of grading harm reduction evidence and regulatory assurances of longitudinal surveillance systems to document the impact of harm reduction policies.

The sodium iodide symporter (NIS) as well-characterized theranostic gene represents an outstanding tool to target different cancer types allowing noninvasive imaging of functional NIS expression and therapeutic radioiodide application. Based on its overexpression on the surface of most cancer types, the cMET/hepatocyte growth factor receptor serves as ideal target for tumor-selective gene delivery. Sequence-defined polymers as nonviral gene delivery vehicles comprising polyethylene glycol (PEG) and cationic (oligoethanoamino) amide cores coupled with a cMET-binding peptide (cMBP2) were complexed with NIS-DNA and tested for receptor-specificity, transduction efficiency, and therapeutic efficacy in hepatocellular cancer cells HuH7. In vitro iodide uptake studies demonstrated high transduction efficiency and cMET-specificity of NIS-encoding polyplexes (cMBP2-PEG-Stp/NIS) compared to polyplexes without targeting ligand (Ala-PEG-Stp/NIS) and without coding DNA (cMBP2-PEG-Stp/Antisense-NIS). Tumor recruitment and vector biodistribution were investigated in vivo in a subcutaneous xenograft mouse model showing high tumor-selective iodide accumulation in cMBP2-PEG-Stp/NIS-treated mice (6.6 ± 1.6% ID/g 123I, biological half-life 3 hours) by 123I-scintigraphy. Therapy studies with three cycles of polyplexes and 131I application resulted in significant delay in tumor growth and prolonged survival. These data demonstrate the enormous potential of cMET-targeted sequence-defined polymers combined with the unique theranostic function of NIS allowing for optimized transfection efficiency while eliminating toxicity.

Cities are vital for achieving the Sustainable Development Goals (SDG), but different local strategies to advance on the same SDG may cause different ‘spillovers’ elsewhere. Research efforts that support governance of such spillovers are urgently needed to empower ambitious cities to ‘account globally’ when acting locally on SDG implementation strategies.