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sharing appear as the most common recurring problems in mass casualty incidents (MCIs). Recent HEPEs, which allowed teams, interdisciplinary groups, and different agencies to practice responding to similar simulated incidents, were important and informed actions during the real response. Immediate and delayed psychosocial support should be in place for healthcare staff responding to MCIs.In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB-IV tumor-node-metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB-IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. SIGNIFICANCE Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis.See related commentary by Zitvogel and Kroemer, p. 224.This article is highlighted in the In This Issue feature, p. 211.

CSF loss in spontaneous intracranial hypotension disrupts a well-regulated equilibrium. We aimed to evaluate the volume shift between intracranial compartments in patients with spontaneous intracranial hypotension before and after surgical closure of the underlying spinal dural breach.

In total, 19 patients with spontaneous intracranial hypotension with a proved spinal CSF leak investigated at our institution between July 2014 and March 2017 (mean age, 41.8 years; 13 women) were included. Brain MR imaging-based volumetry at baseline and after surgery was performed with FreeSurfer. In addition, the spontaneous intracranial hypotension score, ranging from 0 to 9, with 0 indicating very low and 9 very high probability of spinal CSF loss, was calculated.

Total mean ventricular CSF volume significantly increased from baseline (15.3 mL) to posttreatment MR imaging (18.0 mL), resulting in a mean absolute and relative difference, +2.7 mL and +18.8% (95% CI, +1.2 to +3.9 mL;

< .001). The change was apparens the restoration of an equilibrium within the CSF compartment.

To explore stressors and support system for families with a neonate admitted with a systemic infection.

Qualitative study using in-depth interviews (IDIs), based on principles of grounded theory.

A busy level III neonatal unit of a tertiary care teaching hospital in coastal Karnataka, India, between May 2018 and January 2019.

Parents and accompanying attendants of neonates admitted to the neonatal unit with one or more systemic infections.

Using purposive sampling, semi-structured IDIs were audio recorded, transcribed verbatim and a thematic analysis was performed.

Thirty-eight participants were interviewed, lasting between 30 and 59 min. Babies' hospitalisation with sepsis was an unprecedented, sudden and overwhelming event. Stressors related to uncertainties due to the information gap inherent to the nature of illness, cultural rituals, financial constraints, barriers to bonding and others. Parents reported experiencing insomnia, gastric disturbances and fatigue. Support (emotional and/or financ who are particularly vulnerable to stress.

Idiopathic nephrotic syndrome is the most common glomerular disease in children. The majority of patients respond well to steroids. However, the relapse rate is high and many develop steroid dependency. Although other immunosuppressive medicines are successfully used as steroid-sparing agents, some children still have frequent relapsing episodes. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in treating difficult frequently relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). Data on the effectiveness and long-term treatment outcomes of repeated courses of RTX are, however, scarce.

Children and young people with FR/SDNS, aged 1-18 years, who received RTX at Great Ormond Street Hospital (GOSH) from 2006 to 2018 were reviewed.

During these 12 years, 103 children with FR/SDNS received RTX infusions at GOSH. Among these, 58 cases needed repeated courses of RTX 2, 3, 4, 5, 6 and 7 repeated courses were given to 21, 21, 7, 5, 1 and 3 patients, respectively. The overall median time to relapse post-RTX was 11 months (range 1-53 months). There was no change in relapse-free interval with subsequent courses of RTX. No difference was found between age groups, genders and ethnicities. No severe side effects were noted.

RTX seems to be safe even after several repeated courses. However, long-term follow-up and further studies are needed, with a focus on side-effects in particular.

RTX seems to be safe even after several repeated courses. However, long-term follow-up and further studies are needed, with a focus on side-effects in particular.Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH.Background COVID-19 presented significant challenges to healthcare organisations, which needed to rapidly remodel their services but were unable to allow staff to meet face to face to minimise infection risk. During this communication predicament, National Health Service (NHS) Digital announced the provision of Microsoft Teams, a digital communication and collaboration tool, which was implemented at Royal Free London NHS Foundation Trust within 2 weeks.Method Given the need to deploy at scale, rapidly and with minimal resource, an agile decentralised innovation management approach was used, empowering staff to be local implementors.Results Resulting use cases were highly original and varied, ranging from a COVID-19 Education Programme to coordination of oxygen demand. Analytics showed rapid and persistent adoption, surpassing 500 daily active users within 11 days. Usage continues to increase, consistent with a direct network effect.Conclusion These findings suggest a high demand for this format of communication and high willingness to adopt it. Further qualitative research into staff perceptions would be valuable to confirm this, and to assess the user experience.Overall, this has been a radical approach to digital implementation in healthcare, and has so far proved effective in delivering a cost minimal, rapid communication tool at scale in the midst of a global pandemic.Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. For instance, the majority of patients with sporadic amyotrophic lateral sclerosis (up to 97%) and a substantial proportion of patients with frontotemporal lobar degeneration (~45%) exhibit TDP-43 positive neuronal inclusions, suggesting a role for this protein in disease pathogenesis. In addition, TDP-43 inclusions are evident in familial ALS phenotypes linked to multiple gene mutations including the TDP-43 gene coding (TARDBP) and unrelated genes (eg, C9orf72). While TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism, determining the pathophysiological mechanisms through which TDP-43 mediates neurodegeneration appears complex, and unravelling these molecular processes seems critical for the development of effective therapies. This review highlights the key physiological functions of the TDP-43 protein, while considering an expanding spectrum of neurodegenerative diseases associated with pathogenic TDP-43 deposition, and dissecting key molecular pathways through which TDP-43 may mediate neurodegeneration.

To evaluate the association between pregravid use of a variety of contraceptive methods and subsequent fecundability.

Prospective cohort study.

Denmark and North America, 2007-19.

17 954 women who had tried to conceive for up to six menstrual cycles at study entry. At baseline, participants reported their contraceptive histories, and personal, medical, and lifestyle characteristics.

Pregnancy, determined by bimonthly follow-up questionnaires for up to 12 months.

Approximately 38% (n=6735) of participants had recently used oral contraceptives, 13% (n=2398) had used long acting reversible contraceptive methods, and 31% (n=5497) had used barrier methods. Women who had recently stopped using oral contraceptives, the contraceptive ring, and some long acting reversible contraceptive methods experienced short term delays in return of fertility compared with users of barrier methods. Use of injectable contraceptives was associated with decreased fecundability compared with use of barrier methods (fecundability ratio 0.65; 95% confidence interval 0.47 to 0.89). Users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), followed by users of patch contraceptives (four cycles), users of oral and ring contraceptives (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles). Lifetime length of use of hormonal contraceptive methods was not associated with fecundability.

Use of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on fecundability.

Use of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on fecundability.

Several studies have argued a causal relationship between diabetes and depression, while others have highlighted that their association is a result of common risk factors. Because Mexico is a country with a high prevalence of diabetes, and diabetes and depression are a frequent comorbidity, we chose this country to investigate the longitudinal relationship of these two conditions, focusing on the influence of demographic, health, and socioeconomic factors which could act as common risk factors for both conditions.

Using the harmonized Mexican Health and Aging Study, a nationally representative sample of adults older than 50 with a response rate of 93%, we analyzed the longitudinal relationship of diabetes and depressive symptoms using 'between-within' random-effects models, focusing on the effect of demographic, socioeconomic and health factors.

While older adults with diabetes reported a higher prevalence of depressive symptoms in the four waves of the study, there was no causal longitudinal association between them once controlling for demographic, socioeconomic and health factors (between-effect OR=0.