Differences in hip bone mineral density may explain the hip fracture pattern in osteoarthritic hips

Introduction In patients with osteoarthritis of the hip (OAH), trochanteric fractures are much more common than femoral neck fractures. One reason may be altered bone composition in the proximal femurs. OAH often leads to a fixed external rotation of the hip, leading to difficulties in positioning during DXA measurements. We compared BMD in OAH-affected legs and healthy legs

Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium

Purpose: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. Materials and methods: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. Results: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). Conclusion: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors

Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case– control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk

Sorting Signals, N-Terminal Modifications and Abundance of the Chloroplast Proteome

Characterization of the chloroplast proteome is needed to understand the essential contribution of the chloroplast to plant growth and development. Here we present a large scale analysis by nanoLC-Q-TOF and nanoLC-LTQ-Orbitrap mass spectrometry (MS) of ten independent chloroplast preparations from Arabidopsis thaliana which unambiguously identified 1325 proteins. Novel proteins include various kinases and putative nucleotide binding proteins. Based on repeated and independent MS based protein identifications requiring multiple matched peptide sequences, as well as literature, 916 nuclear-encoded proteins were assigned with high confidence to the plastid, of which 86% had a predicted chloroplast transit peptide (cTP). The protein abundance of soluble stromal proteins was calculated from normalized spectral counts from LTQ-Obitrap analysis and was found to cover four orders of magnitude. Comparison to gel-based quantification demonstrates that ‘spectral counting’ can provide large scale protein quantification for Arabidopsis. This quantitative information was used to determine possible biases for protein targeting prediction by TargetP and also to understand the significance of protein contaminants. The abundance data for 550 stromal proteins was used to understand abundance of metabolic pathways and chloroplast processes. We highlight the abundance of 48 stromal proteins involved in post-translational proteome homeostasis (including aminopeptidases, proteases, deformylases, chaperones, protein sorting components) and discuss the biological implications. N-terminal modifications were identified for a subset of nuclear- and chloroplast-encoded proteins and a novel N-terminal acetylation motif was discovered. Analysis of cTPs and their cleavage sites of Arabidopsis chloroplast proteins, as well as their predicted rice homologues, identified new species-dependent features, which will facilitate improved subcellular localization prediction. No evidence was found for suggested targeting via the secretory system. This study provides the most comprehensive chloroplast proteome analysis to date and an expanded Plant Proteome Database (PPDB) in which all MS data are projected on identified gene models

Implementation of the measure of case discussion complexity to guide selection of prostate cancer patients for multidisciplinary team meetings

Background: Multidisciplinary team meetings (MDTMs) provide an integrated team approach to ensure individualized and evidence-based treatment recommendations and best expert advice in cancer care. A growing number of patients and more complex treatment options challenge MDTM resources and evoke needs for case prioritization. In this process, decision aids could provide streamlining and standardize evaluation of case complexity. We applied the recently developed Measure of Case Discussion Complexity, MeDiC, instrument with the aim to validate its performance in another healthcare setting and diagnostic area as a means to provide cases for full MDTM discussions. Methods: The 26-item MeDiC instrument evaluates case complexity and was applied to 364 men with newly diagnosed prostate cancer in Sweden. MeDiC scores were generated from individual-level health data and were correlated with clinicopathological parameters, healthcare setting, and the observed clinical case selection for MDTMs. Results: Application of the MeDiC instrument was feasible with rapid scoring based on available clinical data. Patients with high-risk prostate cancers had significantly higher MeDiC scores than patients with low or intermediate-risk cancers. In the total study, population affected lymph nodes and metastatic disease significantly influenced MDTM referral, whereas comorbidities and age did not predict MDTM referral. When individual patient MeDiC scores were compared to the clinical MDTM case selection, advanced stage, T3/T4 tumors, involved lymph nodes, presence of metastases and significant physical comorbidity were identified as key MDTM predictive factors. Conclusions: Application of the MeDiC instrument in prostate cancer may be used to streamline case selection for MDTMs in cancer care and may complement clinical case selection

Beta 2-agonists administered by a dry powder inhaler can be used in acute asthma

Patients with acute asthma attending the emergency room were included in a double-blind, double-dummy and parallel group study to investigate whether a dry powder inhaler (Turbuhaler) can be used in acute asthma. If so, the aim was to establish the potency relationship between a beta 2-agonist (salbutamol) administered by the dry powder inhaler and the pressurized metered-dose inhaler (pMDI). Eighty-six patients with a mean age of 38 years and forced expiratory volume in 1 s (FEV1) of 37% of predicted normal value were randomized at Siriraj Hospital in Bangkok to either Turbuhaler (50 micrograms dose -1) or pMDI (100 micrograms dose -1) with spacer (Volumatic). Doses of 100 + 300 + 300 + 300 micrograms salbutamol were given at 0, 15, 30 and 45 min via Turbuhaler and repeated at 90, 105, 120 and 135 min (total dose 2000 micrograms). The same inhalation schedule with identical number of doses was used for the pMDI with spacer but in double doses (total 4000 micrograms), assuming a dose-potency ratio of salbutamol administered via Turbuhaler compared with the pMDI of 2:1. At 85 min after the first dose, 60 mg prednisolone was given orally. FEV1 was measured 10 min after each dosing. Peak inspiratory flow (PIF) through Turbuhaler was measured on each dosing occasion. Plasma (P)-salbutamol, serum (S)-potassium concentrations, pulse rate, blood pressure and adverse events were recorded. No statistically significant differences were observed in the increase in FEV1 between the groups: 55 min (165 min) after the first dose, the increase was 0.47 l and 47% (0.64 l and 63%) in the Turbuhaler group, and 0.46 l and 42% (0.68 l and 65%) in the pMDI group. Mean PIF though Turbuhaler was 49 l min -1 (range 26-68) at first inhalation and increased to 60 l min -1 (range 38-86). There was no correlation between the initial PIF through Turbuhaler and the initial FEV1 response. P-salbutamol and S-potassium values correlated well. A larger decrease in S-potassium was noticed after 75 min in the pMDI group (0.38 mmol l -1) compared with the Turbuhaler group (0.23 mmol l -1) (P = 0.02). In conclusion, the use of a dry powder inhaler, Turbuhaler, was investigated in the emergency room treatment of acute asthma, and was as effective as a pMDI with spacer. Half the dose of salbutamol administered via Turbuhaler was as effective as the full dose given via a pMDI with spacer

Scientific Committee on Emerging and Newly Identified Health Risks SCENIHR Risk Assessment of Products of Nanotechnologies

Three independent non-food Scientific Committees provide the Commission with the scientific advice it needs when preparing policy and proposals relating to consumer safety, public health and the environment. The Committees also draw the Commission's attention to the new or emerging problems which may pose an actual or potential threat. They are: the Scientific Committee on Consumer Products (SCCP), the Scientific Committee on Health and Environmental Risks (SCHER) and the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) and are made up of external experts. In addition, the Commission relies upon the work of the European Food Safety Authority (EFSA), the European Medicines Evaluation Agency (EMEA), the European Centre for Disease prevention and Control (ECDC) and the European Chemicals Agency (ECHA). SCENIHR Questions concerning emerging or newly-identified risks and on broad, complex or multidisciplinary issues requiring a comprehensive assessment of risks to consumer safety or public health and related issues not covered by other Community risk-assessment bodies. In particular, the Committee addresses questions related to potential risks associated with interaction of risk factors, synergic effects, cumulative effects, antimicrobial resistance, new technologies such as nanotechnologies, medical devices, tissue engineering, blood products, fertility reduction, cancer of endocrine organs, physical hazards such as noise and electromagnetic fields and methodologies for assessing new risks. Scientific Committee member

Risk and mortality of testicular cancer in patients with neurodevelopmental or other psychiatric disorders

BackgroundBoth testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT.MethodThis is a nested case-control study including 6166 TGCT patients diagnosed during 1992-2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death.ResultsHistory of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09-2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death.ConclusionsWe report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders