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In conclusion, EB2 coordinates MT cytoskeleton and intracellular signal transduction, forming an EB2-MT-ERK positive feedback loop, to facilitate HCC proliferation, invasion and metastasis. EB2 could serve as a promising prognostic biomarker and potential therapeutic target for HCC; HCC patients with high EB2 expression may benefit from treatment with ERK inhibitors.Since the early days of vaccination, targeted immunotherapy has gone through multiple conceptual changes and challenges. It now provides the most efficient and up-to-date strategies for either preventing or treating infections and cancer. Its most recent and successful weapons are autologous T cells carrying chimeric antigen receptors, engineered purposely for binding cancer-specific antigens and therefore used for so-called adoptive immunotherapy. We now face the merger of such achievements in cell therapy using lymphocytes redirected on purpose to bind specific antigens and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) revolution, which conferred genome-editing methodologies with both safety and efficacy. This unique affiliation will soon and considerably expand the scope of diseases susceptible to adoptive immunotherapy and of immune cells available for being reshaped as therapeutic tools, including B cells. Following the monumental success story of passive immunotherapy with monoclonal antibodies (mAbs), we are thus entering into a new era, where a combination of gene therapy/cell therapy will enable reprogramming of the patient's immune system and notably endow his B cells with the ability to produce therapeutic mAbs on their own.The inclusion of mutation status improved risk stratification for newly diagnosed patients with chronic myelomonocytic leukemia (CMML). Stem cell transplantation is a potentially curative treatment option, and patient selection is critical because of relevant transplant-related morbidity and mortality. We aimed to evaluate the impact of mutation status together with clinical presentations on posttransplant outcome. Our study included 240 patients with a median follow-up of 5.5 years. A significant association with worse survival was identified for the presence of mutations in ASXL1 and/or NRAS. In multivariable analysis, ASXL1- and/or NRAS-mutated genotype (hazard ratio [HR], 1.63), marrow blasts >2% (HR, 1.70), and increasing comorbidity index (continuous HR, 1.16) were independently associated with worse survival. A prognostic score (CMML transplant score) was developed, and the following points were assigned 4 points for an ASXL1- and/or NRAS-mutated genotype or blasts >2% and 1 point each for an increase of 1 in the comorbidity index. The CMML transplant score (range, 0-20) was predictive of survival and nonrelapse mortality (P 10. The score retained performance after validation (concordance index, 0.68) and good accuracy after calibration. Predictions were superior compared with existing scores designed for the nontransplant setting, which resulted in significant risk reclassification. This CMML transplant score, which incorporated mutation and clinical information, was prognostic in patients specifically undergoing transplantation and may facilitate personalized counseling.

This is a phase III, double-blind, randomized, controlled trial.

In this trial, patients with laparoscopic colectomy were assigned to either low pressure (LP 7 mmHg) or standard pressure (SP 12 mmHg) at a ratio of 1  1. The aim of this trial was to assess the impact of low-pressure pneumoperitoneum during laparoscopic colectomy on postoperative recovery. The primary endpoint was the duration of hospital stay. The main secondary endpoints were postoperative pain, consumption of analgesics and postoperative morbidity.

Some 138 patients were enrolled, of whom 11 were excluded and 127 were analysed 62 with LP and 65 with SP. Duration of hospital stay (3 versus 4 days; P = 0.010), visual analog scale (0.5 versus 2.0; P = 0.008) and analgesic consumption (level II 73 versus 88 per cent; P = 0.032; level III 10 versus 23 per cent; P = 0.042) were lower with LP. Morbidity was not significantly different between the two groups (10 versus 17 per cent; P = 0.231).

Using low-pressure pneumoperitoneum in laparoscopic colonic resection improves postoperative recovery, shortening the duration of hospitalization and decreasing postoperative pain and analgesic consumption. This suggests that low pressure should become the standard of care for laparoscopic colectomy.

NCT03813797.

NCT03813797.

Age-related sensorineural hearing loss is a common health problem among adults. Nearly 16% of US adults 18 years or older report difficulty hearing. selleck kinase inhibitor The prevalence of perceived hearing loss increases with age. Hearing loss can adversely affect an individual's quality of life and ability to function independently and has been associated with increased risk of falls, hospitalizations, social isolation, and cognitive decline.

To update its 2012 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on screening for hearing loss in adults 50 years or older.

Asymptomatic adults 50 years or older with age-related hearing loss.

Because of a lack of evidence, the USPSTF concludes that the benefits and harms of screening for hearing loss in asymptomatic older adults are uncertain and that the balance of benefits and harms cannot be determined. More research is needed.

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for hearing loss in older adults. (I statement).

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for hearing loss in older adults. (I statement).

Hearing loss is common in older adults and associated with adverse health and social outcomes.

To update the evidence review on screening for hearing loss in adults 50 years or older to inform the US Preventive Services Task Force.

MEDLINE, Cochrane Library, EMBASE, and trial registries through January 17, 2020; references; and experts; literature surveillance through October 8, 2020.

English-language studies of accuracy, screening, and interventions for screen-detected or newly detected hearing loss.

Dual review of abstracts, full-text articles, and study quality. Meta-analysis of screening test accuracy studies.

Quality of life and function, other health and social outcomes, test accuracy, and harms.

Forty-one studies (N = 26 386) were included, 18 of which were new since the previous review. One trial enrolling US veterans (n = 2305) assessed the benefits of screening; there was no significant difference in the proportion of participants experiencing a minimum clinically important difference ans (n = 684) found a significant difference considered to represent a minimal important difference (>18.7 points). Few trials reported on other eligible outcomes, and no studies reported on harms of screening or interventions.

Several screening tests can adequately detect hearing loss in older adults; no studies reported on the harms of screening or treatment. Evidence showing benefit from hearing aids on hearing-related function among adults with screen-detected or newly detected hearing loss is limited to studies enrolling veterans.

Several screening tests can adequately detect hearing loss in older adults; no studies reported on the harms of screening or treatment. Evidence showing benefit from hearing aids on hearing-related function among adults with screen-detected or newly detected hearing loss is limited to studies enrolling veterans.

Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice.

To describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs).

Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US).

Receiving IMV.

Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associatioifference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]).

In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally.

ClinicalTrials.gov Identifier NCT03955874.

ClinicalTrials.gov Identifier NCT03955874.

Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events.

To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients.

The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents.

Tracheal intubation.

The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from ality was 32.8%.

In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.

In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.

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