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Key Clinical Message Negative pressure wound therapy (NPWT) aided in the management of complex soft tissue injury in a 14‐year‐old girl by managing moisture, reducing oedema, and stimulating wound granulation less than 2 months after the accident and prepared the skin for skin grafting, thus successfully saving the limb. Abstract This case study describes the use of a tubular bandage encompassing the whole limb to deliver successful NPWT in the treatment and reconstruction of extensive soft tissue damage extending from the right lower extremity to the hip in a 14‐year‐old female.

ObjectivesEndothelial injury may promote declining lung function. We aimed to investigate in well-treated persons living with HIV (PLWH) whether elevated levels of thrombomodulin (TM) and syndecan-1 (SDC1) are associated with excess lung function decline and worsening dyspnea.MethodsA prospective cohort study comprising patients from the Copenhagen municipality. We included 698 PLWH with undetectable viral load. Biomarkers and demographics were measured at baseline, spirometry [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and dyspnea score both at baseline and 2-year follow-up.Both biomarkers were dichotomized at the 3rd quartile. Decline in lung function was estimated using a linear mixed model with patient-specific random effect. Increase in dyspnea score was estimated using a general mixed logistic regression model.ResultsWe did not find an association between elevated SDC1 or TM and an excess decline in neither FEV1: SDC1: 4.5 mL/year (95% CI: −3.9–12.9, p = 0.30), TM: 2.2 mL/year (95% CI: −6.0–10.4, p = 0.60) nor FVC: SDC1: 4.1 mL/year (95% CI: −6.0–14.2, p = 0.42), TM: 1.4 mL/year (95% CI: −8.3–11.1, p = 0.78). A subgroup analysis of never-smokers was consistent with the main analysis.Likewise, we did not find any association between elevated SDC1 and TM and increase in dyspnea score: SDC1: OR 1.43 (95% CI: 0.89–2.30, p = 0.14), TM: OR 1.05 (95% CI: 0.65–1.71, p = 0.26).ConclusionWe did not find a significant association between elevated biomarkers of endothelial injury and decline in lung function nor dyspnea.

The objective of this study was to evaluate a high-resolution deep-learning (DL)-based diffusion-weighted imaging (DWI) sequence for breast magnetic resonance imaging (MRI) in comparison to a standard DWI sequence (DWIStd) at 1.5 T. It is a prospective study of 38 breast cancer patients, who were scanned with DWIStd and DWIDL. Both DWI sequences were scored for image quality, sharpness, artifacts, contrast, noise, and diagnostic confidence with a Likert-scale from 1 (non-diagnostic) to 5 (excellent). The lesion diameter was evaluated on b 800 DWI, apparent diffusion coefficient (ADC), and the second subtraction (SUB) of the contrast-enhanced T1 VIBE. SNR was also calculated. Statistics included correlation analyses and paired t-tests. High-resolution DWIDL offered significantly superior image quality, sharpness, noise, contrast, and diagnostic confidence (each p < 0.02)). Artifacts were significantly higher in DWIDL by one reader (M = 4.62 vs. 4.36 Likert scale, p < 0.01) without affecting the diagnostic confidence. SNR was higher in DWIDL for b 50 and ADC maps (each p = 0.07). Acquisition time was reduced by 22% in DWIDL. The lesion diameters in DWI b 800DL and Std and ADCDL and Std were respectively 6% lower compared to the 2nd SUB. A DL-based diffusion sequence at 1.5 T in breast MRI offers a higher resolution and a faster acquisition, including only minimally more artefacts without affecting the diagnostic confidence.

Over 200 health journals call on the United Nations, political leaders, and health professionals to recognise that climate change and biodiversity loss are one indivisible crisis and must be tackled together to preserve health and avoid catastrophe. This overall environmental crisis is now so severe as to be a global health emergency.

No abstract available.

Abstract Background An early appropriate response is the cornerstone of treatment for invasive meningococcal disease. Little evidence exists on how cases with invasive meningococcal disease present at first contact to emergency medical services. Methods Retrospective observational study of cases presenting with invasive meningococcal disease from January 1st of 2016 to December 31st of 2020 in the Capital Region of Denmark with a catchment area population of 1,800,000. A single medical emergency center provides services to the region. Data was collected from emergency medical services’ call audio files, data from the call receiver registrations, registrations from ambulance personal and electronic health record data from the hospitalization. Results Of 1527 cases suspected of meningitis, 38 had invasive meningococcal disease and had been in contact with the emergency service. Most contacts were to the medical helpline rather than the emergency call center at initial contact to emergency medical services. All were hospitalized within 12 h. At initial contact, fever was present in 28 (74%) of 38 cases, while specific symptoms such as headache (n=12 (32%)), a rash or petechiae (n=9 (23%)) and stiffness of the neck (n=4 (11%)) varied and were infrequent. Cases younger than 18 years of age were more often male and more often presented with fever and rash/petechiae. Only 4 (11%) received prehospital antibiotic treatment. Conclusions Cases with invasive meningococcal disease presented with fever and unspecific symptoms. Although few were acutely ill at their initial contact, all were admitted within 12 h. We suggest that all feverish cases should be systematically asked about specific symptoms and should be wary of symptom progression to optimize the early management if cases with invasive meningococcal disease.

La publicación de este artículo es una iniciativa organizada por la Alianza Global por el Clima y la Salud (GCHA, por sus siglas en inglés) a través de la Alianza de Salud del Reino Unido sobre el Cambio Climático (UKHACC, por sus siglas en inglés) y los miembros del Grupo de Trabajo Latinoamericano sobre Cambio Climático y Salud. La convocatoria tiene un doble objetivo: que los líderes mundiales acuerden los cambios necesarios para mantener el aumento de la temperatura global por debajo de 1,5°C y que los profesionales de la salud adquieran una mayor relevancia en el debate global sobre la crisis climática y la pérdida de la biodiversidad. La convocatoria se desarrolla en el contexto de la próxima celebración de la Asamblea General de Naciones Unidas que se iniciará el 14 de septiembre de 2021, así como también de la celebración de la conferencia climática COP26 que este año se realizará en Glasgow. Este artículo, cuya autoría pertenece principalmente a editores de 18 prestigiosas revistas científicas ampliamente representativas de los continentes y disciplinas de la salud del mundo, ya ha sido publicada simultáneamente en más de 200 revistas científicas internacionales (https://www.bmj.com/content/full-list-authors-and-signatories-climate-emergency-editorial-september-2021). En esta ocasión, la Revista Argentina de Salud Pública se suma a esta iniciativa conjunta a través de la publicación del artículo en español, con el fin de promover su difusión en los países de la Región. El editorial expresa también la necesidad de restablecer la diversidad biológica y proteger la salud, y de que los países de altos ingresos hagan mayores recortes en sus emisiones de carbono y transfieran fondos a los países de ingresos bajos y medianos. Además, exhorta a la intervención de los gobiernos en el rediseño de los sistemas de transporte, las ciudades, la producción y distribución de alimentos, los mercados para las inversiones financieras, los sistemas de salud, entre otros aspectos, lo que redundaría en amplios beneficios para la salud.

Summary: Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

This study investigated the image quality and choice of ultra-high b-value of two DWI breast-MRI research applications. The study cohort comprised 40 patients (20 malignant lesions). In addition to s-DWI with two m-b-values (b50 and b800) and three e-b-values (e-b1500, e-b2000, and e-b2500), z-DWI and IR m-b1500 DWI were applied. z-DWI was acquired with the same measured b-values and e-b-values as the standard sequence. For IR m-b1500 DWI, b50 and b1500 were measured, and e-b2000 and e-b2500 were mathematically extrapolated. Three readers used Likert scales to independently analyze all ultra-high b-values (b1500–b2500) for each DWI with regards to scan preference and image quality. ADC values were measured in all 20 lesions. z-DWI was the most preferred (54%), followed by IR m-b1500 DWI (46%). b1500 was significantly preferred over b2000 for z-DWI and IR m-b1500 DWI (p = 0.001 and p = 0.002, respectively). Lesion detection was not significantly different among sequences or b-values (p = 0.174). There were no significant differences in measured ADC values within lesions between s-DWI (ADC: 0.97 [±0.09] × 10−3 mm2/s) and z-DWI (ADC: 0.99 [±0.11] × 10−3 mm2/s; p = 1.000). However, there was a trend toward lower values in IR m-b1500 DWI (ADC: 0.80 [±0.06] × 10−3 mm2/s) than in s-DWI (p = 0.090) and z-DWI (p = 0.110). Overall, image quality was superior and there were fewer image artifacts when using the advanced sequences (z-DWI + IR m-b1500 DWI) compared with s-DWI. Considering scan preferences, we found that the optimal combination was z-DWI with a calculated b1500, especially regarding examination time.

ABSTRACT: Background: COVID-19 morbidity and mortality remains high and the need for safe and effective drugs continues despite vaccines. Methods: Double-blind, placebo-controlled, multi-centre, randomised, parallel group phase 2 trial to evaluate safety and efficacy of oral angiotensin II type 2 receptor agonist C21 in hospitalized patients with COVID-19 and CRP ≥ 50-150 mg/L conducted at eight sites in India (NCT04452435). Patients were randomly assigned 100 mg C21 bid or placebo for 7 days in addition to standard of care. Primary endpoint: reduction in CRP. The study period was 21 July to 13 October 2020. Findings: 106 patients were randomised and included in the analysis (51 C21, 55 placebo). There was no significant group difference in reduction of CRP, 81% and 78% in the C21 and placebo groups, respectively, with a treatment effect ratio of 0.85 [90% CI 0.57, 1.26]. In a secondary analysis in patients requiring supplemental oxygen at randomisation, CRP was reduced in the C21 group compared to placebo. At the end of the 7-day treatment, 37 (72.5%) and 30 (54.5%) of the patients did not require supplemental oxygen in the C21 and placebo group, respectively (OR 2.20 [90% CI 1.12, 4.41]). A post hoc analysis showed that at day 14, the proportion of patients not requiring supplemental oxygen was 98% and 80% in the C21 group compared to placebo (OR 12.5 [90% CI 2.9, 126]). Fewer patients required mechanical ventilation (one C21 patient; four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one vs three in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated. Interpretation: Among hospitalised patients with COVID-19 receiving C21 for 7 days there was no reduction in CRP compared to placebo. However, a post-hoc analysis indicated a marked reduction of requirement for oxygen at day 14. The day 14 results from this study justify further evaluation in a Phase 3 study and such a trial is currently underway. Funding: Vicore Pharma AB and LifeArc, UK.

En septiembre del 2021, la Asamblea General de las Naciones Unidas reunirá a los países en un momento crucial para organizar la acción colectiva con el propósito de hacer frente a la crisis medioambiental mundial. Se reunirán una vez más en la Conferencia de las Naciones Unidas sobre la Diversidad Biológica, en Kunming (China) y en la Conferencia de las Naciones Unidas sobre el Cambio Climático (CP26), en Glasgow (Escocia). Antes de la celebración de estas reuniones trascendentales, nosotros —los editores de revistas sobre salud de todo el mundo— exigimos medidas urgentes para mantener los aumentos promedio de la temperatura a nivel mundial por debajo de 1,5 °C, detener la destrucción de la naturaleza y proteger la salud.

No abstract available.

Joint editorial calling for emergency action to limit global temperature increases, restore biodiversity, and protect health.

Abstract Objectives: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism. The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. Hypothesis: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. Trial design: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. Participants: The trial will recruit 1,500 HCW at Danish hospitals. To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week. A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. Main outcomes: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation. Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation. Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1. Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference. The physicians administering the treatment are not blinded. Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group. Trial Status: Current protocol version 5.1, from July 6, 2020. Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. Trial registration: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. Keywords: COVID-19, Randomised controlled trial, Protocol, BCG vaccine, NSEs/Non-specific effects of vaccines, Heterologous effects of vaccines, Health care workers, Pandemic, Immune training.

Background: To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI). Methods: A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18–70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥102 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014–001321-32. Findings: 180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895). Interpretations: A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI. Primary funding source: The Danish Regions [no. 14/217]. Keywords: Cystitis, AUC, UTI, Amdinocillin pivoxil, Pivmecillinam, RCT

Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline.

Summary: Background: Menstrual tampons are widely used in western countries. Indirect evidence suggests that tampon misuse could be associated with an increased risk of menstrual toxic shock syndrome (MTSS). The aim of this study was to determine what characteristics of tampon use are associated with increased risk of menstrual toxic shock syndrome (MTSS). Methods: A nationwide, case-control study in France, was conducted with women that use tampons with MTSS diagnoses according to the CDC diagnostic criteria (n = 55, from January 2011, to December 2017) and a control group of women with no MTSS history (n = 126, from February to December 2017). Information regarding tampon use during a 6-month period was collected. Associations between tampon use and MTSS were assessed using logistic regression models stratified by residential area. Findings: Compared to controls, women diagnosed with MTSS more frequently reported maximum tampon wear of >6 h (62% vs. 41%; P = 0.02), overnight tampon use (77% vs. 54%; P = 0.006), and neither read nor followed tampon instructions in case of reading (65% vs. 42%; P = 0.006). In univariate analysis, MTSS risk was two-fold higher with tampon use for >6 consecutive hours (odds ratio, 2.3 [95% CI, 1.2–4.5]), and three-fold higher with tampon use during sleep for >8 h (odds ratio, 3.2 [95% CI, 1.4–7.7]). In multivariate logistic regression analysis, only maximum tampon use for >6 h (odds ratio, 2.03 [95% CI, 1.04–3.98]), and neither read nor followed the tampon instructions in case of reading (odds ratio, 2.25 [95% CI, 1.15–4.39]) were independently associated with MTSS. Interpretation: Our study suggests that the risk of MTSS was associated with using tampons for more than 6 h, overnight tampon use during sleep, and neither read nor followed tampon insertion instructions in case of reading. Funding: LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon within the programme “Investissements d'Avenir” (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR). Keywords: Staphylococcus aureus, Menstrual toxic shock syndrome, Tampons, Tampon use, Case-control study

This prospective study aimed to investigate the ability of spiral ultrashort echo time (UTE) and compressed sensing volumetric interpolated breath-hold examination (CS-VIBE) sequences in magnetic resonance imaging (MRI) compared to conventional VIBE and chest computed tomography (CT) in terms of image quality and small nodule detection. Patients with small lung nodules scheduled for video-assisted thoracoscopic surgery (VATS) for lung wedge resection were prospectively enrolled. Each patient underwent non-contrast chest CT and non-contrast MRI on the same day prior to thoracic surgery. The chest CT was performed to obtain a standard reference for nodule size, location, and morphology. The chest MRI included breath-hold conventional VIBE and CS-VIBE with scanning durations of 11 and 13 s, respectively, and free-breathing spiral UTE for 3.5–5 min. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and normal structure visualizations were measured to evaluate MRI quality. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. Inter-reader and inter-modality reliability analyses were performed using the Cohen κ statistic and the nodule size comparison was performed using Bland–Altman plots. Among 96 pulmonary nodules requiring surgery, the average nodule diameter was 7.7 ± 3.9 mm (range: 4–20 mm); of the 73 resected nodules, most were invasive cancer (74%) or pre-invasive carcinoma in situ (15%). Both spiral UTE and CS-VIBE images achieved significantly higher overall image quality scores, SNRs, and CNRs than conventional VIBE. Spiral UTE (81%) and CS-VIBE (83%) achieved a higher lung nodule detection rate than conventional VIBE (53%). Specifically, the nodule detection rate for spiral UTE and CS-VIBE reached 95% and 100% for nodules >8 and >10 mm, respectively. A 90% detection rate was achieved for nodules of all sizes with a part-solid or solid morphology. Spiral UTE and CS-VIBE under-estimated the nodule size by 0.2 ± 1.4 mm with 95% limits of agreement from −2.6 to 2.9 mm and by 0.2 ± 1.7 mm with 95% limits of agreement from −3.3 to 3.5 mm, respectively, compared to the reference CT. In conclusion, chest CT remains the gold standard for lung nodule detection due to its high image resolutions. Both spiral UTE and CS-VIBE MRI could detect small lung nodules requiring surgery and could be considered a potential alternative to chest CT; however, their clinical application requires further investigation.

Proper specimen collection is the most important step to ensure accurate testing for the coronavirus disease 2019 (COVID-19) and other infectious diseases. Assessment of healthcare workers’ upper respiratory tract specimen collection skills is needed to ensure samples of high-quality clinical specimens for COVID-19 testing. This study explored the validity evidence for a theoretical MCQ-test and checklists developed for nasopharyngeal (NPS) and oropharyngeal (OPS) specimen collection skills assessment. We found good inter-item reliability (Cronbach’s alpha = 0.76) for the items of the MCQ-test and high inter-rater reliability using the checklist for the assessment of OPS and NPS skills on 0.86 and 0.87, respectively. The MCQ scores were significantly different between experts (mean 98%) and novices (mean 66%), p < 0.001, and a pass/fail score of 91% was established. We found a significant discrimination between checklist scores of experts (mean 95% score for OPS and 89% for NPS) and novices (mean 50% score for OPS and 36% for NPS), p < 0.001, and a pass/fail score was established of 76% for OPS and 61% for NPS. Further, the results also demonstrated that a group of non-healthcare educated workers can perform upper respiratory tract specimen collection comparably to experts after a short and focused simulation-based training session. This study, therefore, provides validity evidence for the use of a theoretical and practical test for upper respiratory specimens’ collection skills that can be used for competency-based training of the workers in the COVID-19 test centers.

Background: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). Methods: Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and IMD, mortality and pneumococcal serotypes was investigated. Results: 372 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were included. We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672 controls. The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20–2.36), but not bacteremia (aOR 1.08; 95% CI: 0.86–1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. Conclusions: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis.

Abstract Mitochondrial dysfunction and alterations in energy metabolism have been implicated in a variety of human diseases. Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin‐2 (PHB2) at the mitochondrial inner membrane. Here, we provide a link between PHB2 deficiency and hyperactive insulin/IGF‐1 signaling. Deletion of PHB2 in podocytes of mice, terminally differentiated cells at the kidney filtration barrier, caused progressive proteinuria, kidney failure, and death of the animals and resulted in hyperphosphorylation of S6 ribosomal protein (S6RP), a known mediator of the mTOR signaling pathway. Inhibition of the insulin/IGF‐1 signaling system through genetic deletion of the insulin receptor alone or in combination with the IGF‐1 receptor or treatment with rapamycin prevented hyperphosphorylation of S6RP without affecting the mitochondrial structural defect, alleviated renal disease, and delayed the onset of kidney failure in PHB2‐deficient animals. Evidently, perturbation of insulin/IGF‐1 receptor signaling contributes to tissue damage in mitochondrial disease, which may allow therapeutic intervention against a wide spectrum of diseases.

Abstract This training session involves a didactic session and hands-on training sessions in the evaluation and management of intrapartum fetal heart rate patterns on a high-fidelity mannequin. The most common prelude to most obstetric emergencies is fetal intolerance of labor, typically demonstrated by changes in the fetal heart rate. For a newly starting OB-GYN resident this can be among the most stressful early experiences on the labor and delivery ward. Proper interpretation and management of the fetal heart rate tracing (FHT) is a critical skill for the obstetric provider that is traditionally acquired through exposure to static images of FHTs and hands-on clinical experience on the labor and delivery ward. The advent of high-fidelity simulators, in particular the Noelle pregnant mannequin, allows for the lifelike simulation of intrapartum fetal heart rate patterns of multiple etiologies. This didactic curriculum uniformly educates obstetric providers in the evaluation and management of intrapartum fetal heart rate patterns and the Noelle high-fidelity pregnancy and delivery simulator, which will allow those providers to do this in a realistic fashion and setting.

Abstract Shoulder dystocia is an obstetric emergency complicating 0.3%-1% of all deliveries. It can lead to permanent disability or death of the neonate and, on occasion, serious morbidity of the mother. Though frequently associated with higher birth weights, 50% of shoulder dystocias occur in normally grown neonates, making prediction of shoulder dystocia difficult. Shoulder dystocia occurs when descent of the neonate's anterior shoulder is obstructed by the mother's pubic symphysis and on occasions when the posterior shoulder is obstructed by the sacral promontory. Because this emergency can occur unpredictably with any pregnancy, all delivery attendants must have an understanding and a management plan for it. This resource is designed to give obstetric care providers an opportunity to train and practice the hand movements required to manage a shoulder dystocia. As severe shoulder dystocia is an uncommon event, a provider may go years without a real-life experience. Safe delivery of an infant suffering a shoulder dystocia requires several crucial steps. Learners in this course appropriately identify shoulder dystocia, call needed backup support, communicate the situation to the mother, perform the steps to relieve the shoulder dystocia, and accurately document the event. One of the great challenges to simulation training is demonstrating the effort put toward simulating clinical care results in a measurable improvement in patient care. Shoulder dystocia simulation is one of the few models that has overcome this challenge. Simulation of shoulder dystocia reduces delivery time, improves timeliness of interventions, and improves performance of the necessary maneuvers. Clinically, this results in a reduction of perinatal asphyxia and neonatal ischemic encephalopathy. The model itself is low tech and reusable, making it ideal for training programs. The significance of our work is that few, if any, research papers studying simulation training provide adequate information about the intervention for educators interested in applying the technology to their training program. Our curriculum provides didactic materials, including video examples on the simulator, and guidelines for administration of a simulated shoulder dystocia event as well as the necessary evaluation forms and documentation.