Abstract Objective Signal-transducer and activator of transcription protein 3 ( STAT3 ) gene encodes a transducer and transcription factor that plays an important role in many cellular processes such ...as cell growth, apoptosis and immune response. Several STAT3 genetic variants have been associated to different autoimmune diseases. Our aim was to reveal the possible STAT3 influence in other immune-mediated diseases such as psoriatic arthritis (PsA) and Behcet disease (BD). Methods The STAT3 rs744166 and rs2293152 polymorphisms were genotyped using predesigned TaqMan® assays in a total of 335 PsA patients, 217 BD patients, and 1844 ethnically matched healthy controls of Spanish Caucasian origin. Results A statistically significant association of the STAT3 rs744166∗ G allele with PsA was observed ( P -value = 1.36 × 10−3 , OR 1.35). The detected effect was more evident when the rs744166∗ GG homozygote frequencies were compared between PsA patients and controls (genotype P -value = 9.77 × 10−5 , OR 1.82). In contrast, the allele and genotypic distributions of rs744166 polymorphism showed no significant differences between patients with BD and control subjects (allelic P -value = 0.80, OR 1.03). Additionally, no evidence of association was detected between the rs2293152 genetic variant and both studied diseases. Conclusion Our results suggest for the first time that the STAT3 gene might be involved in PsA but not in Behcet’s disease predisposition.
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Introduction
Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Underlying mechanisms are poorly known and usually multifactorial. Its ...treatment is not well defined, mostly based in platelet transfusion. Thus, is important to identify new strategies to manage this important post-SCT complication. Romiplostim and Eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Some studies with very small number of cases have reported their potential efficacy in the allo-SCT setting. For this reason, the aim of our study is to analyze the efficacy and safety of TPO-RAs for severe and persistent thrombocytopenia after allo-SCT.
Patients and methods
We performed a retrospective multicenter study including patients from centers of GETH with prolonged isolated thrombocytopenia (PT) or secondary failure of platelet recovery (SFPR) after allo-SCT. PT was defined as the engraftment of all peripheral blood cell lines but with platelet count ≤20000/µL for 7 consecutive days or requirement of transfusion for more than 60 days after allo-SCT. SFPR was defined as a decline of platelet counts to ≤20000/µL for 7 consecutive days or requirement of transfusion after achievement platelets ≥50000/µL without transfusion for 7 days post-SCT. The primary endpoint was platelet recovery to ≥50000/µL.
Results
Eighty-six patients with thrombocytopenia after allo-SCT were included. The characteristic of the patients, are summarized in table 1. Sixteen (19%) of the patients had PT and 71 (82%) SFPR. TPO-RA was started at a median time of 127 days (27-1177) after allo-SCT (41% Romiplostim / 59% Eltrombopag). Median initial and maximum administered doses were 50 mg/daily (25-150) and 75 (25-150) for Eltrombopag and 1 µg/kg (1-7) and 5 (1-10) for Romiplostin, respectively. Eighteen patients (21%) were previously treated with cell infusion (67% mesenchymal cells and 33% CD34+ boost). Median platelet count before TPO-RA onset was 14000/µL (1000-57000). Platelet recovery to ≥50000/µL was 60% and the response was achieved at a median time of 56 days (2-247). Responses were similar considering all potential causes of thrombocytopenia evaluated. 81% of the patients had decrease number of megakaryocytes prior to treatment showing a worse response to therapy: median time to ≥20000/µL platelets 43 days versus 28 days (p=0.011), with also a lower rate of platelet recovery to ≥50000/µL (62% versus 85% if normal megakaryocytes). In patients treated with Eltrombopag, 27% had neutropenia <1000/µL and 74% achieved >1000/µL after therapy. The median treatment duration was 62 days (7-700) and 62% discontinued TPO-Ra maintaining response. Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the cases. At last follow up with a median of 10 months (1-59), 72% of the patients maintained the response and 61 (71%) were alive. Death rate was significantly lower in responder-patients to TPO-RAs, 15% versus 53% in non-responders (p<0.001). Causes of death were disease progression (28%), infections (48%), graft versus host disease (GvHD) (16%) and others (8%).
Conclusion
To our knowledge this is the biggest series analyzing the use of TPO-Ra after allo-SCT. Our results support the efficacy and safety in this new setting with responses around 60% and a low number of side effects. Additional studies to identify predictors of response are needed.
Display omitted
No relevant conflicts of interest to declare.
Objective
The objective of this observational, descriptive, cross-sectional, multicentre study was to assess the perceived quality and grade of satisfaction expressed by patients with chronic ...arthropathies regarding the use of musculoskeletal (MSK) ultrasonography by rheumatologists as an integrated clinical care tool.
Methods
All Spanish rheumatology departments with MSK ultrasonography incorporated in their healthcare services were invited to participate in the study. A Spanish-language survey was offered to fill out anonymously to all consecutive patients with chronic arthropathies under follow-up in the rheumatology outpatient clinics who attended their centre for a period of 3 months. The survey consisted of three sections. The first section contained patients’ demographics, disease data, frequency of performing rheumatological ultrasound and information about who performed their ultrasound assessments. The second section consisted of 14 questions about patient’s experience and opinion on different aspects of the management, performance and perceived usefulness of performing ultrasound, to be answered on a Likert scale 1–5. The third section of the survey was addressed to the rheumatologist ultrasonographers.
Results
Nine hundred and four patients from 16 university hospital rheumatology departments completed the survey. All questions reached an overall favourable response ≥ 80%. Patients who reported usual ultrasound examinations in their rheumatology care and those in which it was their attending rheumatologist who performed the ultrasound assessments responded more favourably.
Conclusion
Our encouraging patient-centred results may be useful in facilitating the implementation of rheumatological ultrasound in rheumatology care worldwide.
Key Points
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This is the largest multicentre survey carried out in patients with chronic joint diseases designed to assess their experience and perceived benefits with the use of ultrasonography performed by rheumatologists in daily practice.
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Musculoskeletal ultrasound incorporated into rheumatology care was very well accepted and valued by most patients.
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The patients perceived that ultrasonography helps not only their rheumatologist but also themselves to better understand their condition.
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The patients believed that ultrasonography helps them accept and comply with the proposed treatment.
Purpose of Review
To summarize and discuss the available evidence and ongoing efforts in order to establish the efficacy and safety of immunotherapeutic approaches in HER2-positive breast cancer.
...Recent Findings
The introduction into the clinic of anti-HER2–targeted therapies more than 15 years ago resulted in a substantial improvement in the outcome of patients with HER2-overexpressing breast cancer. However, only patients with the highest levels of HER2 expression will potentially benefit from these therapies and, unfortunately, many patients progress or relapse after optimal treatment. As metastatic breast cancer remains an incurable disease, new therapeutic strategies are urgently needed to improve clinical outcomes in these patients. Immunotherapy is emerging as a new treatment modality in breast cancer. Although it has long been regarded as a non-immunogenic disease, new preclinical and clinical studies have emphasized the therapeutic potential of the use of anti-HER2 therapies in combination with immune checkpoint inhibitors in improving outcomes in breast cancer patients.
Summary
Emerging results from clinical trials evaluating immunotherapeutic agents, either as monotherapy or in combination with anti-HER2–targeted therapies, are showing promising results in the management of HER2-positive breast cancer.
The aim of the present randomized trial was to compare high-dose therapy (HDT) with continued conventional chemotherapy in patients with multiple myeloma (MM) who responded to the initial treatment. ...From May 1994 to October 1999, 216 patients (122 men/94 women; stage II or III; Eastern Cooperative Oncology Group ECOG score less than 3) entered the study. Initial chemotherapy consisted of 4 cycles of alternating vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, Adriamycin, dexamethasone (VBMCP/VBAD). Responding patients were randomly assigned to receive 8 additional cycles of VBMCP/VBAD, intensification with melphalan 200 mg/m2, or melphalan 140 mg/m2 plus 12 Gy fractionated total body irradiation (TBI). One-hundred sixty-four patients were randomly assigned, 83 to continued chemotherapy and 81 to HDT. The complete remission (CR) rate was significantly higher with HDT (30% vs 11%; P = .002). However, progression-free survival (PFS) was not significantly different between HDT and conventional therapy (median, 42 vs 33 months; P = not significant NS), and overall survival (OS) was similar in both groups (median, 61 vs 66 months). Finally, survival after relapse was identical in the 2 arms (15.9 vs 16.4 months). In conclusion, these results show that HDT intensification, when given to myeloma patients who have responded to the initial chemotherapy, significantly increases the CR rate but has no significant impact on PFS or OS.
Objective: The aim of the current study is to develop and obtain valid evidence for a hazard perception test suitable for the Spanish driving population. To obtain valid evidence to support the use ...of the test, the effect of hazardous and quasi-hazardous situations on the participants' hazard prediction is analyzed and the pattern of results for drivers with different driving experience-that is, learner, novice, and expert drivers and reoffender vs. nonoffender drivers-is compared. Potentially hazardous situations are those that develop without involving any real hazard (i.e., the driver did not actually have to decelerate or make any evasive maneuver to avoid a potential collision). The current study analyzed repeat offender drivers attending compulsory reeducation programs as a result of reaching the maximum number of penalty points on their driving license due to repeated violations of traffic laws.
Method: A new video-based hazard perception test was developed, using a total of 20 hazardous situation videos plus 8 quasi-hazardous situation videos. They were selected from 167 recordings of natural hazards in real Spanish driving settings.
Results: The test showed adequate psychometric properties and evidence of validity, distinguishing between different types of drivers. Psychometric results confirm a final version of the hazard perception test composed of 11 video clips of hazards and 6 video clips of quasi-hazards, for which an overall Cronbach's alpha coefficient of.77 was obtained. A lack of ability to detect quasi-hazards and distinguish them from hazardous situations was also found for learner, novice, and reoffender drivers. Learner drivers obtained lower average scores than novice and experienced drivers with the hazardous situation videos, and learner drivers obtained lower average scores than experienced drivers with the quasi-hazardous situation videos, suggesting that the ability to correctly identify hazardous traffic situations may develop early by accumulating initial driving experience. However, the ability to correctly identify quasi-hazardous situations may develop later with the accumulation of further driving experience. Developing this ability is also difficult for reoffender drivers.
Conclusion: The test has adequate psychometric properties and is useful in distinguishing between learner, novice, and expert drivers. In addition, it is useful in that it analyzes the performance of both safe and unsafe drivers (reoffenders who have already lost their driving license).
Background/Aim: The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the ...effects of AdoMet treatment in human alcoholic liver cirrhosis.
Methods: A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg/day, orally) or placebo for 2 years. All patients had alcoholic cirrhosis, and histologic confirmation of the diagnosis was available in 84% of the cases. Seventy-five patients were in Child class A, 40 in class B, and 8 in class C. Sixty-two patients received AdoMet and 61 received placebo.
Results: At inclusion into the trial no significant differences were observed between the two groups with respect to sex, age, previous episodes of major complications of cirrhosis, Child classification and liver function tests. The overall mortality/liver transplantation at the end of the trial decreased from 30% in the placebo group to 16% in the AdoMet group, although the difference was not statistically significant (
p=0.077). When patients in Child C class were excluded from the analysis, the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group (29%
vs 12%,
p=0.025), and differences between the two groups in the 2-year survival curves (defined as the time to death or liver transplantation) were also statistically significant (
p=0.046).
Conclusions: The present results indicate that longterm treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis, especially in those with less advanced liver disease.
Plasmonics in Atomically Thin Crystalline Silver Mkhitaryan, Vahagn; Abd El-Fattah, Zakaria M.; Brede, J. ...
2019 21st International Conference on Transparent Optical Networks (ICTON),
2019-July
Conference Proceeding
Summary from only given. We report on the fabrication of few-atomic-layer-thick wafer-scale crystalline silver films, along with the observation of plasmons in the near-to-mid infrared spectral ...regions upon lithographic structuring. Our measured optical spectra reveal narrow plasmons (quality factor ~ 4), further supported by a low sheet resistance comparable to bulk metal in few-atomic-layer silver films down to 7 Ag(111) monolayers. Good crystal quality and plasmon narrowness are obtained despite the addition of a thin passivating dielectric, which renders our samples resilient to ambient conditions.
According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet's disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 ...has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations.
This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ(2) test.
In addition to HLA-B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be protective. Other HLA-A and B specificities were suggestive of association with the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58). Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs in IL10 were found to be significantly associated with susceptibility to BD in our population.
Different HLA specificities are associated with Behçet's disease in addition to B*51. Other non-HLA genes, such as IL23R and IL-10, play a role in the susceptibility to the disease.
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