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Metaplastic breast cancer (MpBC) is a rare tumor representing 1% of all breast malignancies. The prognosis of this histologic subtype is actually poor and there are no current clear-cut therapeutic guidelines. Hence, despite its uniqueness, its aggressive prognostic profile strongly encourages further studies to identify new markers and therapeutic targets. Herein, we report a case of 32-years-old patient affected with of triple negative spindle-shaped MpBC. The research of molecular targets on the primary tumor did not allow performing an effective therapeutic choice. Extracellular Vesicles (EVs) are under intense study as new potential pathophysiological markers and targets for therapeutic applications, in different tumors for their role in tumor onset, progression and aggressiveness. Here, we examined the involvement of EVs in this case, to look into the MpBC microenvironment willing to identify new potential molecular targets, pathways of aggressiveness, and markers of prognosis and therapeutic efficacy. Firstly, we characterized MpBC patient EV dimensions and surface proteins. Moreover, we analyzed the EV RNA cargo supposed to be delivered to nearby and distant recipient cells. Interestingly, we observed a dysregulation EV-contained miRNAs, which could determine an increased expression of oncogenes in the tumor microenvironment, probably enabling cancer progression. These data suggest that the characterization of miRNA cargo of EVs could be important for the identification of new markers and for the application of future new target therapies.

Growing evidence added to the results from observational studies of lung cancer patients exhibiting eosinophilia. However, whether eosinophils contributed to tumor immune surveillance or neoplastic evolution was unknown. This study aimed to analyze the causal association between eosinophilia and lung cancer.

The causal effect of eosinophil count on lung cancer from a genome-wide association study (GWAS) was investigated using the two-sample Mendelian randomization (MR) method. Secondary results according to different histological subtypes of lung cancer were also implemented. Meanwhile, we compared the measured levels of blood eosinophil counts among different subtypes of lung cancer from real-world data.

The median absolute eosinophilic count (unit 10

/L) [median (min, max) Lung adenocarcinoma 0.7 (0.5, 15); Squamous cell lung cancer 0.7 (0.5, 1.3); Small cell lung cancer 0.7 (0.6, 1.3);

= 0.96] and the median eosinophil to leukocyte ratio [median (min, max) Lung adenocarcinoma 8.7% (2.1, 42.2%); Squamous cell lung cancer 9.3% (4.1, 17.7%); Small cell lung cancer 8.9% (5.1, 24.1%);

= 0.91] were similar among different histological subtypes of lung cancer. MR methods indicated that eosinophilia may provide 28% higher risk for squamous cell lung cancer in East Asian [Weighted median method odds ratio (OR) = 1.28, 95% CI 1.04-1.57,

= 0.02].

Our study suggested that eosinophilia may be a potential causal risk factor in the progression of squamous cell lung cancer in East Asian.

Our study suggested that eosinophilia may be a potential causal risk factor in the progression of squamous cell lung cancer in East Asian.

Since its approval for adults with moderate-to-severe atopic dermatitis (AD) in 2017, dupilumab has been incorporated into clinical practice guidelines (CPGs). However, recommendations differ internationally, and the quality assessment of their development is unclear.

We aimed to systematically review and appraise the quality of CPGs for adult AD reported since 2017 and map the recommendations for dupilumab initiation relative to conventional systemic therapy (CST).

A literature search was conducted in June 2020 in MEDLINE, EMBASE, SCOPUS, and CINAHL. Twelve CPGs were retrieved. Methodological quality was assessed using the validated Appraisal of Guidelines for Research & Evaluation II tool (AGREE-II). Recommendations were extracted and compared.

AGREE-II median scores per domain of the CPGs were (%, r = range) scope/purpose, 78% (50-96); stakeholder involvement, 54% (28-85); rigor of development, 39% (21-63); clarity of presentation, 85% (69-100); applicability, 27% (6-51); and editorial independab relative to CST, while one did not reach consensus. Our findings highlight divergent recommendations AD treatment, underlining a need to incorporate quality criteria into future guideline development.

Dupilumab is now incorporated into CPGs for adult AD. These CPGs exhibited good quality in scope/purpose, clarity, and editorial independence domains. However, none met AGREE-II criteria for methodological rigor/applicability. Gaps were found in mechanisms for updates, facilitators/barriers, resource implications, and stakeholder involvement. Only n = 3/12 CPGs met quality criteria for recommendation without modifications. Of these, two favored a conservative sequential approach for the initiation of dupilumab relative to CST, while one did not reach consensus. Our findings highlight divergent recommendations AD treatment, underlining a need to incorporate quality criteria into future guideline development.

The relationship between serum cholesterol and mortality remains disputed. This study aimed to examine the association of low and high-density lipoprotein cholesterol (LDL-C and HDL-C) with all-cause mortality among community-dwelling older adults in the Shanghai Aging Study.

We followed 3,239 participants free of lipid-lowering agents for a median of 10 years. Levels of LDL-C and HDL-C were measured at baseline using fasting blood samples. Survival status was confirmed by the local mortality surveillance system. The associations between the levels of LDL-C, HDL-C, and all-cause mortality were assessed by Cox proportional hazards models.

The increment of LDL-C concentration was related to a lower risk of mortality (

for trend < 0.05). Using the highest quintile of LDL-C (≥4.10 mmol/L) as a reference, the lowest quintile of LDL-C (<2.61 mmol/L) was associated with the highest risk of mortality, after adjusting for confounders (HR 1.67; 95% CI 1.26-2.21), exclusion of death within the first 2 yearound an inverse association of LDL-C and a U-shape relationship of HDL-C with long-term all-cause mortality in a cohort with community-dwelling older Chinese adults. Levels of LDL-C and HDL-C are suggested to be managed properly in late life.

Systematic data on the efficacy and safety of COVID-19 vaccine in patients on renal replacement therapy (RRT) remains limited. We conducted a meta-analysis on the efficacy and safety of COVID-19 vaccine in patients on RRT.

Eligible studies were identified by systematic literature search in four electronic databases. Twenty-seven studies (4,264 patients) were included for meta-analysis. 99% patients received mRNA vaccine.

Patients on RRT showed inferior seropositivity after two-dosed COVID-19 vaccine, 44% lower than the general population. Kidney transplant recipients (KTRs) had significantly lower seropositivity than patients on haemodialysis (HD) or peritoneal dialysis (PD) (26.1 vs. 84.3% and 92.4% respectively,

< 0.001 for both). Compared with healthy controls, KTRs, HD and PD patients were 80% (95% CI 62-99%), 18% (95% CI 9-27%) and 11% (95% CI 1-21%) less likely to develop antibodies after vaccination (

< 0.001, <0.001 and 0.39 respectively). In KTRs, every 1% increase in using mycophenolate was associated with 0.92% reduction in seropositivity (95% CI -1.68, -0.17,

= 0.021) at population level. find more The overall adverse event rate attributed to vaccination was 2.1%. Most events were mild.

Patients on RRT, particularly KTRs, had significantly reduced antibody response after two-dosed COVID-19 vaccination. Vaccination is generally well tolerated.

https//www.crd.york.ac.uk/prospero/, identifier CRD42021261879.

https//www.crd.york.ac.uk/prospero/, identifier CRD42021261879.

To evaluate hyperopia-correcting phototherapeutic keratectomy (HC-PTK) and to compare the visual and refractive outcomes of HC-PTK and conventional PTK.

This study comprised a total of 72 eyes of 72 consecutive patients who underwent HC-PTK and conventional PTK for granular corneal dystrophy or band-shaped keratopathy. Preoperatively and 6 months postoperatively, we assessed visual acuity, manifest refraction, and mean keratometry, as well as postoperative corneal higher-order aberrations and adverse events in each PTK group, and compared these metrics between the two groups.

LogMAR BSCVA significantly improved from 0.43 ± 0.47 preoperatively to 0.21 ± 0.38 postoperatively in the HC-PTK group (Wilcoxon signed-rank test,

< 0.001). It was also significantly improved from 0.22 ± 0.21 preoperatively to 0.15 ± 0.12 postoperatively in the conventional PTK group (

= 0.031). Mean refraction significantly changed from 0.27 ± 1.55 diopter (D) preoperatively to 0.50 ± 1.77 D postoperatively, in the HC-PTK group (

= 0.313). By contrast, it was significantly hyperopic from -0.15 ± 2.41 D preoperatively to 1.45 ± 2.46 D postoperatively, in the conventional PTK group (

< 0.001). No significant complications occurred in any case during the follow-up period.

Both HC-PTK and conventional PTK showed a significant improvement of BSCVA and no vision-threatening complications at any time in this series. HC-PTK significantly reduced a hyperopic shift in refraction compared with conventional PTK, suggesting its viability for patients requiring PTK, especially in consideration of preventing this hyperopic issue.

Both HC-PTK and conventional PTK showed a significant improvement of BSCVA and no vision-threatening complications at any time in this series. HC-PTK significantly reduced a hyperopic shift in refraction compared with conventional PTK, suggesting its viability for patients requiring PTK, especially in consideration of preventing this hyperopic issue.Cystic fibrosis (CF) is the most common rare disease caused by a mutation of the CF transmembrane conductance regulator gene encoding a channel protein of the apical membrane of epithelial cells leading to alteration of Na+ and K+ transport, hence inducing accumulation of dense and sticky mucus and promoting recurrent airway infections. The most detected bacterium in CF patients is Pseudomonas aeruginosa (PA) which causes chronic colonization, requiring stringent antibiotic therapies that, in turn induces multi-drug resistance. Despite eradication attempts at the first infection, the bacterium is able to utilize several adaptation mechanisms to survive in hostile environments such as the CF lung. Its adaptive machinery includes modulation of surface molecules such as efflux pumps, flagellum, pili and other virulence factors. In the present study we compared surface protein expression of PA multi- and pan-drug resistant strains to wild-type antibiotic-sensitive strains, isolated from the airways of CF patients To our knowledge, this is the first study that, applying a shaving proteomic approach, describes adaptation processes of a large collection of PA clinical strains isolated from CF patients in early and chronic infection phases.

Infective endocarditis (IE) presents with increasing incidence and mortality in some regions and countries, as well as serious socioeconomic burden. The current study aims to compare and interpret the IE burden and temporal trends globally and in different regions from 1990 to 2019.

Data on the incidence, deaths and disability-adjusted life years (DALYs) caused by IE were extracted and analyzed from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPC) were adopted to quantify the change trends of age-standardized rates (ASRs). Besides, potential contributors of serious IE burden were also evaluated including age, gender, social-demographic index (SDI), and age-standardized incident rate (ASIR) in 1990.

Globally, the number of IE cases and deaths has increased sharply during the past 30 years from 478,000 in 1990 to 1,090,530 in 2019 and from 28,750 in 1990 to 66,320 in 2019, and both presented an upward temporal trend annually (EAPC1.2 for incidence and 0.71 for death). However, the EAPC of age-standardized DALYs demonstrated a negative temporal trend despite increasing DALYs from 1,118,120 in 1990 to 1,723,590 in 2019.