Exploitation of parasite-derived antigen in therapeutic success against canine visceral leishmaniosis

The purpose of this study is to quantify the existing interrelationship between the anesthetic substances used in the implanto-prosthetic rehabilitation procedures with the general state of the patient, as well as the specific implant rehabilitation work.The analyzed lot brought together 110 patients, candidates for implanto-prosthetic rehabilitation, subjected to a general and local evaluation protocol for choosing general anesthesia in accordance with the general state and complexity of the implanto-prosthetic algorithm. Regarding connection between therapeutic approaches in oral implantation and types of anesthesia , we obtained correlative aspects between the use of inhalosedation and implantation algorithm in 80% clinical cases and augmentation with implantation was found in 20%.General anesthesia with Midazolam has been correlated with implantation and augmentation in 77% clinical cases and sinus lift and implantation was found in 23% clinical cases.General anesthesia with Midazolam was used in 64% clinical cases with implantation and sinus lift and 36% clinical cases with implantation.Careful monitoring of the patient and proper dental surgery where the intervention is performed are the key for a therapeutic success regarding sedation and anesthesia.

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AB0676 THE ROLE OF ACPA AND ANA IN SPONDYLOARTHRITIS: HOW THE AUTOIMMUNE DYSREGULATION CAN AFFECT THE COURSE OF DISEASE AND THERAPEUTIC SUCCESS OF MONOTHERAPY DMARDS AND bDMARDs

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4526 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1633.1-1633

Author(s):

D. Cici ◽

C. Rotondo ◽

A. Corrado ◽

S. Berardi ◽

N. Mansueto ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Start Time ◽

Disease Manifestation ◽

Therapeutic Success ◽

Course Of Disease ◽

Drug Survival ◽

Comorbidity Index ◽

Citrullinated Protein ◽

Axial Involvement

Background:Occasional findings of anti-citrullinated-protein-antibodies (ACPA) and anti-nuclear-antibodies (ANA) were rarely described in literature on Psoriatic Arthritis (PsA) and on Spondyloarthritis (SpA) in general. How these autoimmune dysregulations can affect the course of them is not yet understood.Objectives:The aim of our study is to evaluate if the presence of ACPA and ANA can determine different disease subsets and influence the DMARDs monotherapy (methotrexate) drug survival (DSM) and b-DMARDs multi-failure patients (MF).Methods:We conducted a retrospective study on patients with Psoriatic Arthritis (PsA) and Spondyloarthritis that fulfilled the ASAS and CASPAR criteria. Patients with diagnosis of connective tissue disease and rheumatoid arthritis and patients ≤ 18 years old were excluded from the study. For each patient, the following variables were considered: age, ACPA, ANA, time between arthritis onset and start of DMARDs (start-time), DSM, switch to b-DMARDs (sw-bDMARDs), arthritis subset (oligoarticular (OA), polyarticular (PA), enthesitis (EA), axial involvement (AI)), number of comorbidities (NC), Charlson Comorbidity Index (CCI).Results:150 patients (55% with PsA and 45% with another SpA) were included in the study. No differences were found in age, ANA rate, ACPA rate, start-time, OA, PA, EA, AI, NC and CCI between the PsA and SpA groups.In the whole group of patients, the ACPA+ subjects(11%) had a significant increase of NC (2.47 ± 1.5 vs 1.6 ± 1.4, p=0.035), a trend to higher CCI, to switch to b-DMARDs, and to be MF compared to those without ACPA. In the same group, the ANA+ patients (12%) showed shorter DSM (233.5 wk ± 45.9 vs 548.0 wk ± 56.8, p=0.362) with similar trend in each subgroup (PsA and SpA).In SpA group, the ACPA+ patients(6,3%) had a trend to shorter DSM (269.0 weeks ± 125vs 603.96 wk± 92.8, p=0.492),to higher sw-bDMARDs, and to be MF, higher NC and CCI compared to those without ACPA. No differences in clinical subset (OA, PA, EA, AI) were observed. In the same group the ANA+ patients had significant higher rate of PA (100% vs 65%, p=0.026) rather than OA (0% vs 35%, p=0.025). No significant differences were found in NC, CCI, MF.In the PsA group, ACPA+ patients showed a trend to develop PA and EA subsets, shorter DSM (187.5 wk ± 48.7 vs 299.6 wk ± 31.4, p=0.415), higher rate to sw-bDMARDs and to be MF. The ANA+ PsA patients had higher trend to develop PA and AI subsets rather than OA and EA. All ANA+ patients were MF (100% vs 42%, p=0.046).Conclusion:The ACPA and ANA positivity in PsA and SpA patients could be suggestive of more severe clinical disease manifestation, higher frequency of comorbidities and lower predicted 10-year survival (CCI). Moreover, this autoimmune dysregulation could be associated with worse drug survival in monotherapy with methotrexate and higher chance to be MF. Therefore, they can be taken into account for clinical management of these patients.Disclosure of Interests:None declared

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Glioblastoma and MiRNAs

Cancers ◽

10.3390/cancers13071581 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1581

Author(s):

Swalih P. Ahmed ◽

Javier S. Castresana ◽

Mehdi H. Shahi

Keyword(s):

Brain Tumors ◽

Human Body ◽

Diagnostic Tool ◽

Poor Prognosis ◽

Treatment Options ◽

Diagnosis And Treatment ◽

Therapeutic Success ◽

Knowing That ◽

Almost All ◽

Cell Signaling Pathways

Glioblastoma (GB) is one of the most common types of lethal brain tumors. Although several treatment options are available including surgery, along with adjuvant chemo and radiotherapy, the disease has a poor prognosis and patients generally die within 14 months of diagnosis. GB is chemo and radio resistant. Thus, there is a critical need for new insights into GB treatment to increase the chance of therapeutic success. This is why microRNA (miRNA) is being potentially considered in the diagnosis and treatment of glioblastoma. The objective of our review is to provide a holistic picture of GB up-regulated and down-regulated miRNA, in relationship with the expression of other genes, cell signaling pathways, and their role in GB diagnosis and treatment. MiRNA treatment is being considered to be used against GB together with radiotherapy and chemotherapy. Moreover, the use of miRNA as a diagnostic tool has also begun. Knowing that miRNAs are isolated in almost all human body fluids and that there are more than 3000 miRNAs in the human genome, plus the fact that each miRNA controls hundreds of different mRNAs, there is still much study needed to explore how miRNAs relate to GB for its proliferation, progression, and inhibition.

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OX40L–OX40 Signaling in Atopic Dermatitis

Journal of Clinical Medicine ◽

10.3390/jcm10122578 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2578

Author(s):

Masutaka Furue ◽

Mihoko Furue

Keyword(s):

T Cells ◽

Atopic Dermatitis ◽

Memory T Cells ◽

Effector Memory ◽

T Helper ◽

T Helper 1 ◽

Therapeutic Success ◽

T Helper 2 ◽

Promising Target ◽

Antigen Presenting

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

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Melanoma Cell Resistance to Vemurafenib Modifies Inter-Cellular Communication Signals

Biomedicines ◽

10.3390/biomedicines9010079 ◽

2021 ◽

Vol 9 (1) ◽

pp. 79

Author(s):

Claudio Tabolacci ◽

Martina Cordella ◽

Sabrina Mariotti ◽

Stefania Rossi ◽

Cinzia Senatore ◽

...

Keyword(s):

Tumor Microenvironment ◽

Acquired Resistance ◽

Bioinformatic Analysis ◽

Interferon Γ ◽

Melanoma Cells ◽

Vascular Endothelial ◽

Therapeutic Success ◽

Communication Signals ◽

Proteasome Pathway ◽

Endothelial Growth Factor

The therapeutic success of BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) in BRAF-mutant melanoma is limited by the emergence of drug resistance, and several lines of evidence suggest that changes in the tumor microenvironment can play a pivotal role in acquired resistance. The present study focused on secretome profiling of melanoma cells sensitive or resistant to the BRAFi vemurafenib. Proteomic and cytokine/chemokine secretion analyses were performed in order to better understand the interplay between vemurafenib-resistant melanoma cells and the tumor microenvironment. We found that vemurafenib-resistant melanoma cells can influence dendritic cell (DC) maturation by modulating their activation and cytokine production. In particular, human DCs exposed to conditioned medium (CM) from vemurafenib-resistant melanoma cells produced higher levels of pro-inflammatory cytokines—that potentially facilitate melanoma growth—than DCs exposed to CM derived from parental drug-sensitive cells. Bioinformatic analysis performed on proteins identified by mass spectrometry in the culture medium from vemurafenib-sensitive and vemurafenib-resistant melanoma cells suggests a possible involvement of the proteasome pathway. Moreover, our data confirm that BRAFi-resistant cells display a more aggressive phenotype compared to parental ones, with a significantly increased production of interferon-γ, interleukin-8, vascular-endothelial growth factor, CD147/basigin, and metalloproteinase 2 (MMP-2). Plasma levels of CD147/basigin and MMP-2 were also measured before the start of therapy and at disease progression in a small group of melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib. A significant increment in CD147/basigin and MMP-2 was observed in all patients at the time of treatment failure, strengthening the hypothesis that CD147/basigin might play a role in BRAFi resistance.

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Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

Antibiotics ◽

10.3390/antibiotics10030263 ◽

2021 ◽

Vol 10 (3) ◽

pp. 263

Author(s):

Carolina Osorio ◽

Laura Garzón ◽

Diego Jaimes ◽

Edwin Silva ◽

Rosa-Helena Bustos

Keyword(s):

Side Effects ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Bacterial Resistance ◽

Plasma Concentrations ◽

Resistant Bacteria ◽

Therapeutic Drug ◽

Therapeutic Success ◽

Favorable Clinical Outcome ◽

And Control

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

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Risk areas for Human Visceral Leishmaniosis 2007–2018: A temporal and spatial analysis in Ceará, Brazil

Zoonoses and Public Health ◽

10.1111/zph.12866 ◽

2021 ◽

Author(s):

Kellyn Kessiene de Sousa Cavalcante ◽

Jarier de Oliveira Moreno ◽

Reagan Nzundu Boigny ◽

Francisco Roger Aguiar Cavalcante ◽

Caroline Mary Gurgel Dias Florêncio ◽

...

Keyword(s):

Spatial Analysis ◽

Risk Areas ◽

Temporal And Spatial ◽

Visceral Leishmaniosis

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480 Cardiovascular and metabolic risk in patients with suspected comorbid insomnia and obstructive sleep apnea (COMISA)

SLEEP ◽

10.1093/sleep/zsab072.479 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A189-A190

Author(s):

Miguel Meira e Cruz ◽

Luana Seixas ◽

Augusto Santos ◽

João Garrido ◽

Yuri Lopes ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

High Risk ◽

Arterial Hypertension ◽

Sleep Time ◽

Comorbid Condition ◽

Therapeutic Success ◽

Comorbid Insomnia ◽

Systemic Arterial Hypertension ◽

Obstructive Sleep

Abstract Introduction Only few studies looked for a possible association of cardiovascular disorders (CVD), in comorbid insomnia with obstructive sleep apnea (COMISA) even though this is a relevant topic in order to prevent one of the major causes of morbimortality. The present study aimed to investigate the association of insomnia symptoms in patients at risk for obstructive sleep apnea in terms of prevalence and clinical interactions and to evaluate the risk of CVD in patients with a risk for COMISA. Methods This is a cross-sectional study. All medical records with data such as age, sex, height, weight and BMI, time to sleep, time to wake up, total sleep time, the Epworth Sleepiness Scale (ESS), STOP-BANG Questionnaires were studied. Insomnia and comorbidities were also investigated, and the patientsanswered yes or no to systemic arterial hypertension, diabetes, CVD. Results 685 patients were enrolled on the present study. We observed that the mild, moderate, and high risk for COMISA presented progressively increasing levels for the frequency of hypertension, diabetes, and CVD. A binary logistic regression was performed to assess whether risk for COMISA could be a predictor for CVD, and it was found that the model containing risk for COMISA was statistically significant: [x2(1)=5.273;p<0.021, R2 Negelkerke=0.014]. Risk for COMISA presented itself as a significant predictor for CVD (OR=1.672; 95% CI=1.079–2.592). Conclusion There was an increased frequency of associated comorbidities such as CVD, systemic arterial hypertension, and diabetes, according to the mild, moderate, or high risk. These findings highlight the need for a cardiometabolic evaluation in patients with this comorbid condition which may impact prognosis and therapeutic success. Support (if any):

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