BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a ...key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1beta, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-beta1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-beta1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy.
Hemoadsorption (HA) might mitigate the systemic inflammatory response associated with post-cardiac arrest syndrome (PCAS) and improve outcomes. Here, we investigated the feasibility, safety and ...efficacy of HA with CytoSorb
in cardiac arrest (CA) survivors at risk of PCAS.
In this pilot randomized controlled trial, we included patients admitted to our intensive care unit following CA and likely to develop PCAS: required norepinephrine (> 0.2 µg/kg/min), and/or had serum lactate > 6 mmol/l and/or a time-to-return of spontaneous circulation (ROSC) > 25 min. Those requiring ECMO or renal replacement therapy were excluded. Eligible patients were randomly allocated to either receive standard of care (SOC) or SOC plus HA. Hemoadsorption was performed as stand-alone therapy for 24 h, using CytoSorb
and regional heparin-protamine anticoagulation. We collected feasibility, safety and clinical data as well as serial plasma cytokines levels within 72 h of randomization.
We enrolled 21 patients, of whom 16 (76%) had out-of-hospital CA. Median (IQR) time-to-ROSC was 30 (20, 45) minutes. Ten were assigned to the HA group and 11 to the SOC group. Hemoadsorption was initiated in all patients allocated to the HA group within 18 (11, 23) h of ICU admission and conducted for a median duration of 21 (14, 24) h. The intervention was well tolerated except for a trend for a higher rate of aPTT elevation (5 (50%) vs 2 (18%) p = 0.18) and mild (100-150 G/L) thrombocytopenia at day 1 (5 (50%) vs 2 (18%) p = 0.18). Interleukin (IL)-6 plasma levels at randomization were low (< 100 pg/mL) in 10 (48%) patients and elevated (> 1000 pg/mL) in 6 (29%). The median relative reduction in IL-6 at 48 h was 75% (60, 94) in the HA group versus 5% (- 47, 70) in the SOC group (p = 0.06).
In CA survivors at risk of PCAS, HA was feasible, safe and was associated with a nonsignificant reduction in cytokine plasma levels. Future trials are needed to further define the role of HA after CA. Those studies should include cytokine assessment to enrich the study population.
NCT03523039, registered 14 May 2018.
Renal replacement therapy (RRT) in critically ill patients is associated with high morbidity and mortality. The appropriateness of RRT initiation is sometimes questioned in elderly patients. ...Therefore, we sought to evaluate the long-term mortality, dialysis dependence and quality of life (QOL) of elderly patients who survived critical illness requiring RRT.
This is a monocentric observational study including all patients > 55 yo who received RRT for acute kidney injury in our intensive care unit (ICU) between January 2015 and April 2018. At the time of the study (May 2019), we assessed if they were still alive by cross referencing our hospital database and the Swiss national death registry. We sent survivors written information and, subsequently, contacted them over the phone. We obtained their consent for participation, asked about their dialytic status and performed an EQ-5D survey with visual analog scale (VAS). Results were stratified according to their age at the time of ICU admission (G1: "55-65 yo"; G2: "> 65-75 yo" and G3: "> 75 yo"). QOL in G3 patients were compared to G1 and G2 and to predicted values.
Among the 352 eligible patients, 171 died during the index hospital admission. After a median follow-up time of 32.7 months (IQR 19.8), a further 62 had died (median time to death for ICU survivors 5.0 (IQR 15.0) months. Hence, 119 (33.6%) patients were still alive at the time of the study. We successfully contacted 96 (80.7%) of them and 83 (69.7%) were included in the study (G1: 24, G2: 44 and G3: 15). Only 6 (7.2%) were RRT dependent. Patients in G3 had lower EQ-5D and VAS scores than those in G1 and G2 (p < 0.01). These scores were also significantly lower than predicted values (p < 0.05).
RRT patients have a very high in-hospital and post discharge mortality. Among survivors, RRT dependency was low. Irrespective of baseline values, patients > 75 yo who survived ICU had a lower QOL than younger patients. It was lower than predicted according to age and sex. The appropriateness of RRT initiation in elderly patients should be discussed according to their pre-existing QOL and frailty.
Varicocele is the primary cause of male infertility and the interests of research about varicocele have changed in the last years. The aim of the study was to analyse how topics of interests about ...varicocele have changed in the last two decades. Literature about paediatric varicocele between 2000 and 2018 was reviewed, and the subjects of the articles were analysed, selecting the main and secondary topics of each article. A study of their prevalence over the years was performed. In the research, 625 articles were found but only 169 provided data in the paediatric age. The total percentage of exclusively paediatric works was 27.04%, being above average in Europe, North and South America. The main subject both for Europe and North America was surgical technique, while for Asia it was videolaparoscopy. The main issue in South America was fertility; Africa and Oceania do not have enough publications to make statistics. Paediatric articles account for less than one‐third of overall articles. The first interest of research is surgical technique. In Europe, the topics seem to exclude fertility potential.
Background and Objective
AtopyReg
®
is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of ...Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis.
Methods
Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed.
Results
A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18–90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients.
Conclusions
This baseline data analysis deriving from AtopyReg
®
provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients’ quality of life.
Cryptorchidism is associated with alteration of fertility potential. The aim of this study is to evaluate mid/long-term morphology and volume of the operated testis for undescended testes by using ...elastosonography.
The medical records of consecutive patients who had received orchiopexy at the Authors' Institution between January 2014 and January 2017 were retrospectively considered. The patients enrolled in the study were divided into different groups depending on their age at the time of the procedure and on the time elapsed from it. The radiological and surgical examinations examined position, volume and trophism of both testes.
During the study period 270 patients received surgery; only 34 patients complied with the inclusion criteria: 19 with right orchiopexy and 15 with left orchiopexy (P > 0.05) (P = 0.57). The mean testicular volume of the operated testis was 0.59 ± 0.32 ml, while the mean testicular volume of non-operated testis was 0.88 ± 0.34 ml (P < 0.05). The elastosonographic comparison between operated and non-operated testis showed that the operated testis had a higher elastosonographic result (grade 2-3) (P < 0.05). Higher grades at elastosonography corresponded to smaller testicular volume.
This study demonstrates that the patient's age at surgery is correlated with significative differences in terms of volume and elasticity (testicular quality). The study also shows that there is not a progressive improvement of elasticity at follow-up.
Abstract
Immune-mediated pathogenesis has been suggested for idiopathic sensorineural hearing loss. Recent studies have investigated the relationship between idiopathic sensorineural hearing loss and ...autoantibodies against inner ear antigens. We conducted a prospective, observational study in a series of pediatric patients affected by idiopathic sensorineural hearing loss. Autoantibodies against inner ear (anti-Cogan peptide, anti-connexin 26, anti-DEP1/CD148 and anti-reovirus), previously described in the serum of patients with Cogan's syndrome, were detected in our population. The characteristics of children whose results were positive were also evaluated to verify if clinical data, disease progression and response to treatment could confirm an immune-mediated pathogenesis. Eleven patients were enrolled and 9 of them were positive for inner ear antibodies. Non-organ specific autoantibodies were present in 5 children out of 9. An immune-mediated condition was diagnosed in 2 cases and minor immune manifestations were found in 2 additional patients. In 5 cases hearing loss remained stable without therapy, while 4 children developed progression. Two subjects were treated with corticosteroids and methotrexate, achieving hearing improvement. Another subject showed stabilization on methotrexate. Inner ear autoantibodies can be positive in children with autoimmune sensorineural hearing loss, and in conjunction with clinical data may assist the clinician in identifying a subset amenable for immune modulation therapy. Large prospective studies are needed to investigate usefulness, diagnostic and prognostic role of these autoantibodies.
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