Tag: pubmed

Sci Transl Med. 2021 Aug 24:eabh2624. doi: 10.1126/scitranslmed.abh2624. Online ahead of print.

ABSTRACT

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN-specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non-COVID-19 controls revealed a lack of type I IFN-stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN-specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN-specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

PMID:34429372 | DOI:10.1126/scitranslmed.abh2624

BMJ Open. 2021 Aug 24;11(8):e051099. doi: 10.1136/bmjopen-2021-051099.

ABSTRACT

INTRODUCTION: Although several authors have been interested in the well-being and social participation of teleworkers in the context of the COVID-19 pandemic, it appears that most of the recommendations issued are based on literature reviews or expert opinions; yet few authors have documented the perspectives of the workers. The aim of this study is to explore workers’ perspectives of teleworking in the context of the COVID-19 pandemic regarding the effects on their well-being and social participation.

METHODS AND ANALYSIS: Using a participatory study protocol involving the collaboration of a community organisation defending workers’ rights, the first step will be to conduct focus groups to qualitatively describe workers’ perspectives of their teleworking conditions. Then, an online questionnaire will be administered to a large pool or workers to quantitatively explore the influence of individual, organisational and environmental variables on the well-being and social participation of workers. The thematic and statistical analyses of the data collected will indicate successful practices to be adopted by workers and organisations. These successful practices will be validated by workers through a Technique for Research of Information by Animation of a Group of Experts group and will serve as concrete tools to better support workers’ participation in teleworking.

ETHICS AND DISSEMINATION: The approval of the research ethics board of the Centre intégré universitaire de santé et de services sociaux de la Capitale Nationale has been obtained. Findings will be shared with various stakeholders including workers, employers, insurers and unions. Findings will be disseminated in webinars, peer-reviewed journals and lectures.

PMID:34429318 | DOI:10.1136/bmjopen-2021-051099

Arch Dis Child. 2021 Aug 24:archdischild-2021-322012. doi: 10.1136/archdischild-2021-322012. Online ahead of print.

ABSTRACT

BACKGROUND: Lead damages most body organs and its effects are most profound in children. In a study in Beirut in 2003, before banning the leaded gasoline, 79% of the participants showed blood lead levels (BLLs) higher than 5 µg/dL. The prevalence of lead exposure in Lebanon after the ban on leaded gasoline has not been studied. This study assessed the BLL in Lebanese children aged 1-6 years.

METHODS: This cross-sectional study was conducted in three hospitals in Beirut. The children’s BLLs were tested, and their caregiver completed a questionnaire to identify subgroups at risk of exposure. Participants were provided with a WHO brochure highlighting the risks of lead.

RESULTS: Ninety children with a mean age of 3.5±1.5 years were enrolled in the study and had a mean BLL of 1.1±0.7 µg/dL, with all values being below 5.0 µg/dL, showing a marked decrease in BLL compared with the mean BLL before the ban on leaded gasoline in 2002. Having a father or a mother with a college degree (p=0.01 and p=0.035, respectively) and having a monthly household income greater than $1000 (p=0.021) were associated with significantly lower BLL. Having more rooms at home and residing close to construction sites were associated with a significantly lower BLL (p=0.001 and p=0.026, respectively). Residing in a house aged >40 years and receiving traditional remedies were associated with a significantly higher BLL (p=0.009 and p<0.0001, respectively).

CONCLUSION: BLLs have declined among Lebanese children and this could be attributed to multiple factors including the ban of leaded gasoline. It would be beneficial to conduct a larger study with a nationally representative sample to better characterise the BLL.

PMID:34429329 | DOI:10.1136/archdischild-2021-322012

BMJ Open. 2021 Aug 24;11(8):e047396. doi: 10.1136/bmjopen-2020-047396.

ABSTRACT

INTRODUCTION: Phosphodiesterase-type 5 inhibitors (PDE5i) are the recommended first-line treatment for erectile dysfunction. Previous systematic reviews and meta-analyses suggest that they are a safe and effective option in many patient groups. Similarly, PDE5i may be effective as part of combination therapy in non-responders to PDE5i. We will generate an overview of systematic reviews, meta-analyses and network meta-analyses aiming to summarise the available knowledge regarding the efficacy and safety of PDE5i in the general population and in multiple subgroups of patients.

METHODS AND ANALYSIS: This overview was designed in accordance with the PRIO-harms and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and its protocol was registered at PROSPERO. We will systematically search PubMed, Web of Science, Cochrane Library and Scopus databases from inception to November 2020 without any language restrictions. We will include systematic reviews or meta-analyses: (1) comparing the efficacy and safety of any dose of PDE5i with each other, with placebo or with other effective treatments for the management of erectile function; (2) exploring the use of any PDE5i alone or in combination with other treatment modalities in the general male population or in specific subgroups and (3) conducted with systematic procedures. Our overview will employ the AMSTAR 2 tool to evaluate the quality of the included studies and the Grading of Recommendations Assessment, Development and Evaluation approach to assess the strength of evidence for all outcomes. We will construct forest plots of risk estimates with the corresponding CI for all outcomes.

ETHICS AND DISSEMINATION: In this overview, we will undertake an extensive literature search in an attempt to evaluate the potential benefits and risks of treatment with one PDE5i versus another or versus placebo and provide recommendations for clinicians and policy-makers. No ethical approval is required.

PROSPERO REGISTRATION NUMBER: CRD42020216754.

PMID:34429310 | DOI:10.1136/bmjopen-2020-047396

Eur Urol Focus. 2021 Aug 21:S2405-4569(21)00217-0. doi: 10.1016/j.euf.2021.08.002. Online ahead of print.

ABSTRACT

BACKGROUND: Three-dimensional (3D) models improve the comprehension of renal anatomy.

OBJECTIVE: To evaluate the impact of novel 3D-derived parameters, to predict surgical outcomes after robot-assisted partial nephrectomy (RAPN).

DESIGN, SETTING, AND PARTICIPANTS: Sixty-nine patients with cT1-T2 renal mass scheduled for RAPN were included. Three-dimensional virtual modeling was achieved from computed tomography. The following volumetric and morphological 3D parameters were calculated: V_T (volume of the tumor); V_T/V_K (ratio between tumor volume and kidney volume); CSA_3D (ie, contact surface area); UCS_3D (contact to the urinary collecting system); Tumor-Artery_3D: tumor’s blood supply by tertiary segmental arteries (score = 1), secondary segmental artery (score = 2), or primary segmental/main renal artery (scoren = 3); S_T (tumor’s sphericity); Conv_T (tumor’s convexity); and Endophyticity_3D (ratio between the CSA_3D and the global tumor surface).

INTERVENTION: RAPN with a 3D model.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three-dimensional parameters were compared between patients with and without complications. Univariate logistic regression was used to predict overall complications and type of clamping; linear regression was used to predict operative time, warm ischemia time, and estimated blood loss.

RESULTS AND LIMITATIONS: Overall, 11 (15%) individuals experienced overall complications (7.2% had Clavien ≥3 complications). Patients with urinary collecting system (UCS) involvement at 3D model (UCS_3D = 2), tumor with blood supply by primary or secondary segmentary arteries (Tumor-Artery_3D = 1 and 2), and high Endophyticity_3D values had significantly higher rates of overall complications (all p ≤ 0.03). At univariate analysis, UCS_3D, Tumor-Artery_3D, and Endophyticity_3D are significantly associated with overall complications; CSA_3D and Endophyticity_3D were associated with warm ischemia time; and CSA_3D was associated with selective clamping (all p ≤ 0.03). Sample size and the lack of interobserver variability are the main limits.

CONCLUSIONS: Three-dimensional modeling provides novel volumetric and morphological parameters to predict surgical outcomes after RAPN.

PATIENT SUMMARY: Novel morphological and volumetric parameters can be derived from a three-dimensional model to describe surgical complexity of renal mass and to predict surgical outcomes after robot-assisted partial nephrectomy.

PMID:34429273 | DOI:10.1016/j.euf.2021.08.002

Dig Liver Dis. 2021 Aug 21:S1590-8658(21)00388-1. doi: 10.1016/j.dld.2021.07.018. Online ahead of print.

ABSTRACT

BACKGROUND: Although several risk factors have been identified for the development of pancreatic cancer, the effects of fruit and vegetables on the disease remains controversial.

METHODS: Individuals without cancer at baseline, who underwent national health examinations during 2008, were enrolled and followed-up to 2017. Vegetable intake was measured by assessing the intake of daily vegetables (types). Fruit intake was also assessed on a weekly basis. We evaluated the risk of pancreatic cancer using adjusted hazard ratio (aHR) and 95% confidence interval (95% CI).

RESULTS: Of 3,605,959 individuals (44% men), pancreatic cancer occurred in 10,469 subjects (5,384 men) during the 9 year follow-up. In adjusted analyses, the daily intake of more than five vegetable types reduced pancreatic cancer compared to no vegetable intake (aHR = 0.82; 95% CI, 0.71-0.94). Using sex-specific analyses, vegetable intake markedly reduced pancreatic cancer in women (aHR = 0.84 for 1-2 vegetable types, 0.84 for 3-4 and 0.69 for ≥ 5), but no effects were observed in men. Sex-specific analyses revealed that fruit intake reduced pancreatic cancer in men (aHR = 0.87 for 3-4 servings/week, and 0.84 for ≥ 7), but no effects were observed in women.

CONCLUSIONS: High intakes of dietary vegetables and fruit reduce pancreatic cancer development in women and men, respectively.

PMID:34429267 | DOI:10.1016/j.dld.2021.07.018

Eur Urol Focus. 2021 Aug 21:S2405-4569(21)00218-2. doi: 10.1016/j.euf.2021.08.003. Online ahead of print.

ABSTRACT

CONTEXT: Retzius sparing robot-assisted radical prostatectomy (RS-RARP) is increasingly being used, but results of pertinent studies on perioperative, functional, and oncological outcomes comparing the Retzius sparing approach with standard robot-assisted radical prostatectomy (RARP) remain inconsistent.

OBJECTIVE: To evaluate the effectiveness of RS-RARP compared with standard RARP, in terms of perioperative, functional, and oncological outcomes.

EVIDENCE ACQUISITION: We performed a systematic search using multiple databases (PubMed, MEDLINE, EMBASE, and Cochrane Central) until March 2021. Only randomized controlled trials (RCTs) and prospective studies were eligible for study inclusion. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were respected. Studies were critically appraised for the risk of bias. Primary outcomes were continence/potency recovery, as well as positive surgical margin (PSM) rates. Secondary outcomes included total intra- and perioperative complication rates.

EVIDENCE SYNTHESIS: Four RCTs and six prospective observational studies were included in this systematic review. The meta-analysis revealed that PSM rates in ≤pT2 tumors were statistically significantly higher, following RS-RARP as compared with RARP (risk ratio [RR]=1.39; 95% confidence interval [CI]=[1.01-1.91]). PSM rates in ≥pT3 tumors tended to be higher following RS-RARP (RR=1.36; 95% CI=[0.74-2.50]), although statistical significance was not reached. Immediate continence recovery was higher and significantly advantageous for RS-RARP (RR=1.81; 95% CI=[1.26-2.60]). Continence recovery also tended to be higher at 3 and 6 mo in the RS-RARP group (RR=1.57; 95% CI=[0.69-3.58] and RR=1.22; 95% CI=[0.89-1.66], respectively). The urinary continence recovery at 12 mo was similar in both groups (RR=1.14; 95% CI=[0.98-1.32]). A meta-analysis of included studies showed no significant difference concerning the return of erectile function and major complication rates between RS-RARP and RARP (RR=1.05; 95% CI=[0.76-1.45] and (RR=0.79; 95% CI=[0.07-8.74], respectively).

CONCLUSIONS: Available data suggest a statistically significant advantage in favor of RS-RARP in terms of immediate urinary continence recovery. PSM rates in localized ≤pT2 tumors are statistically significantly higher following RS-RARP. Potency and serious complication rates appear to be similar.

PATIENT SUMMARY: Our meta-analysis of the current evidence shows a significant advantage for Retzius sparing robot-assisted radical prostatectomy (RS-RARP) over robot-assisted radical prostatectomy in terms of immediate urinary continence recovery, but positive cancer margins are higher following RS-RARP. There was no significant difference in the preservation of erectile function and overall postoperative complication rates between both the techniques.

PMID:34429272 | DOI:10.1016/j.euf.2021.08.003

J Foot Ankle Surg. 2021 Jun 21:S1067-2516(21)00219-2. doi: 10.1053/j.jfas.2021.06.010. Online ahead of print.

ABSTRACT

Arthrodesis of the first metatarsal phalangeal joint (MTPJ) is a widely utilized surgical procedure for a wide array of metatarsal pathologies. This study aims to explore the functional limitations following first MTPJ arthrodesis, overall satisfaction and patient’s abilities to achieve activities of daily living (ADL). This prospective cohort study assessed functional limitations as well as footwear and lifestyle restrictions using several questionnaires. One hundred and three participants who had a first MTPJ arthrodesis under the care of a single surgeon were recruited. Pre- and postoperative patient-reported outcome measures were recorded. The American Orthopaedic Foot and Ankle Score (AOFAS) and the Manchester-Oxford Foot Questionnaire were also used to further examine functional status. Hallux valgus angle (HVA) and intermetatarsal angle (IMA) were compared using preoperative and postoperative weightbearing radiographs and successful fusion was recorded. Complications were documented and are discussed in detail. The duration of follow-up was more than 12 months. There was one nonunion in the cohort while 2 patients experienced delay to fusion. Approximately 97% of patients were very satisfied with the procedure and their ability to achieve ADLs post operatively. A further 82.5% of patients were able to return to wearing nonadaptive footwear. The mean reduction in HVA and IMA was 21.78° and 6.84°, respectively. This study demonstrates the safe and successful use of a compression screw/locking plate construct for arthrodesis of the first MTPJ. Furthermore, the study provides clear evidence of high levels of functionality after the procedure with statistically significant differences (p value <.05) in all 4 facets of the AOFAS questionnaire as well as several notable differences in activity levels and footwear restrictions pre and postoperatively.

PMID:34429264 | DOI:10.1053/j.jfas.2021.06.010

Semin Cell Dev Biol. 2021 Aug 21:S1084-9521(21)00211-1. doi: 10.1016/j.semcdb.2021.08.007. Online ahead of print.

ABSTRACT

The three-dimensional structure of the human genome has been proven to have a significant functional impact on gene expression. The high-order spatial chromatin is organised first by looping mediated by multiple protein factors, and then it is further formed into larger structures of topologically associated domains (TADs) or chromatin contact domains (CCDs), followed by A/B compartments and finally the chromosomal territories (CTs). The genetic variation observed in human population influences the multi-scale structures, posing a question regarding the functional impact of structural variants reflected by the variability of the genes expression patterns. The current methods of evaluating the functional effect include eQTLs analysis which uses statistical testing of influence of variants on spatially close genes. Rarely, non-coding DNA sequence changes are evaluated by their impact on the biomolecular interaction network (BIN) reflecting the cellular interactome that can be analysed by the classical graph-theoretic algorithms. Therefore, in the second part of the review, we introduce the concept of BIN, i.e. a meta-network model of the complete molecular interactome developed by integrating various biological networks. The BIN meta-network model includes DNA-protein binding by the plethora of protein factors as well as chromatin interactions, therefore allowing connection of genomics with the downstream biomolecular processes present in a cell. As an illustration, we scrutinise the chromatin interactions mediated by the CTCF protein detected in a ChIA-PET experiment in the human lymphoblastoid cell line GM12878. In the corresponding BIN meta-network the DNA spatial proximity is represented as a graph model, combined with the Proteins-Interaction Network (PIN) of human proteome using the Gene Association Network (GAN). Furthermore, we enriched the BIN with the signalling and metabolic pathways and Gene Ontology (GO) terms to assert its functional context. Finally, we mapped the Single Nucleotide Polymorphisms (SNPs) from the GWAS studies and identified the chromatin mutational hot-spots associated with a significant enrichment of SNPs related to autoimmune diseases. Afterwards, we mapped Structural Variants (SVs) from healthy individuals of 1000 Genomes Project and identified an interesting example of the missing protein complex associated with protein Q6GYQ0 due to a deletion on chromosome 14. Such an analysis using the meta-network BIN model is therefore helpful in evaluating the influence of genetic variation on spatial organisation of the genome and its functional effect in a cell.

PMID:34429265 | DOI:10.1016/j.semcdb.2021.08.007

Reprod Biomed Online. 2021 Jul 22:S1472-6483(21)00350-3. doi: 10.1016/j.rbmo.2021.07.010. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: Is ovarian stimulation and pregnancy in women with familial adenomatous polyposis (FAP)-associated desmoid tumours safe?

DESIGN: The study included women with FAP-associated desmoid tumours who underwent fertility treatments at the authors’ tertiary medical centre between the years 2011 and 2021. Data were collected from the fertility unit’s charts and from the oncological registries. The main outcome measures were the number of vitrified oocytes and embryos, and the number of live births in preimplantation genetic testing for monogenic/single gene defects (PGT-M) cycles.

RESULTS: Overall, 17 women were identified suitable for this study. A total of 117 mature oocytes were vitrified for fertility preservation and 106 embryos were submitted to PGT-M. One patient returned to claim her cryopreserved oocytes, and five patients who underwent PGT-M embryo transfer reported three live births. A statistically significant decrease in selected fertility cycle parameters was observed in one woman who co-administered sorafenib (a multikinase inhibitor) during her first cycles of treatment, as the mean number of oocytes before and after was 2.7 (±1.3) versus 13.2 (±3.3) (P = 0.02), the mean number of metaphase II oocytes was 2.2 (±2.1) versus 7.7 (±2.6) (P = 0.007), and the mean number of two-pronuclei oocytes was 0.5 (±1.1) versus 3.5 (±1.7) (P = 0.09). Three patients had a median desmoid tumour growth on magnetic resonance imaging of 6.2 (2.9-7.2) cm when compared with prior ovarian stimulation imaging.

CONCLUSIONS: Ovarian stimulation for women with desmoid tumours was characterized in some patients with an acceleration in tumour growth, regardless of the use of aromatase inhibitors. The use of sorafenib should be carefully considered during the course of fertility treatment.

PMID:34429254 | DOI:10.1016/j.rbmo.2021.07.010