A new updated prognostic index for patients with brain metastases (BMs) treated with palliative whole brain radiotherapy (WBRT) in the era of precision oncology. METASNCore project.

INTRODUCTION: Palliative WBRT is the main treatment for multiple BMs. Recent studies report no benefit in survival after WBRT compared to palliative supportive care in patients (pts) with poor prognosis. A new era of systemic treatment strategies based on targeted therapies are improving the prognosis of patients with BMs. The purpose of this study is to develop a prognostic score in palliative pts with BMs who undergo WBRT in this new setting. METHODS: 239 pts with BMs who received palliative WBRT between 2013-2022 in our center were analyzed retrospectively. The score was designed according to the value of the ß coefficient of each variable with statistical significance in the multivariate model using Cox regression. Once the score was established, a comparison was performed according to Kaplan-Meier and was analyzed by log-rank test. RESULTS: 149 pts (62.3%) were male and median (m) age was 60 years. 139 (58,2%) were lung cancer and 35 (14,6%) breast cancer. All patients received 30Gys in 10 sessions. m overall survival (OS) was 3,74 months (ms). 37 pts (15,5%) had a specific target mutation. We found that 62 pts were in group < 4 points with mOS 6,89 ms (CI 95% 3,18-10,62), 84 in group 4-7 points with mOS 4,01 ms (CI 95% 3,40-4,62) and 92 pts in group > 7 points with mOS 2,72 ms (CI 95% 1,93-3,52) (p < 0,001). CONCLUSIONS: METASNCore items are associated with OS and they could be useful to select palliative pts to receive WBRT. More studies are necessary to corroborate our findings.

Bovine mastitis, a worldwide impact disease: Prevalence, antimicrobial resistance, and viable alternative approaches.

Bovine mastitis is globally considered one of the most important diseases within dairy herds, mainly due to the associated economic losses. The most prevalent etiology are bacteria, classified into contagious and environmental, with Staphylococcus aureus, Streptococcus agalactiae, Streptococcus uberis, Escherichia coli and Klebsiella pneumoniae being the most common pathogens associated with mastitis cases. To date these pathogens are resistant to the most common active ingredients used for mastitis treatment. According to recent studies resistance to new antimicrobials has increased, which is why developing of alternative treatments is imperative. Therefore the present review aims to summarize the reports about bovine mastitis along 10 years, emphasizing bacterial etiology, its epidemiology, and the current situation of antimicrobial resistance, as well as the development of alternative treatments for this pathology. Analyzed data showed that the prevalence of major pathogens associated with bovine mastitis varied according to geographical region. Moreover, these pathogens are classified as multidrug-resistant, since the effectiveness of antimicrobials on them has decreased. To date, several studies have focused on the research of alternative treatments, among them vegetal extracts, essential oils, or peptides. Some other works have reported the application of nanotechnology and polymers against bacteria associated with bovine mastitis. Results demonstrated that these alternatives may be effective on bacteria associated with bovine mastitis.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

An assessment of mental health of Mexican and Colombian medical students during the COVID-19 pandemic / Una evaluación de la salud mental de estudiantes de medicina Mexicanos y Colombianos durante la pandemia de COVID-19

Abstract Introduction The COVID-19 pandemic caused the cessation of academic activities from the face-to-face format to confinement and virtual classes, in which little is studied about its effect on mental health. Objective Determine levels of depression, anxiety, and stress in medical students in Mexico and Colombia during the COVID-19 pandemic. Furthermore, depression, anxiety, and stress were compared by gender, education status, and country. Method A cross-sectional study was carried out with 426 medical students. Data was collected using an online survey containing the Depression, Anxiety, Stress Scale (DASS-21) questionnaire. Results Overall scores for depression, anxiety, and stress were 6.7 ± 1.2, 8.8 ± 1.2, and 5.6 ± 1.2, respectively. Females had significantly higher overall scores for depression (.24-fold increase), anxiety (.25-fold increase), and stress (.40-fold increase) than males (p ≤ .01). The risk for anxiety and stress by school year showed that basic years were associated with higher scores than advanced years (.25 and .38-fold increase, respectively). For females, starting medical school did show an increased risk of depression when compared to male students in their basic years (.38-fold increase). Lastly, students from Mexico had an increased risk for depression and anxiety (p ≤ .022 and p ≤ .004, respectively) but not for stress (p ≤ .402), when compared to students from Colombia. Discussion and conclusion Significant anxiety and depression were observed in medical students from Mexico and Colombia. Factors associated with an increased risk of depression and anxiety are students in their basic years as well as being female.

Resumen Introducción La pandemia de COVID-19 provocó el cese de las actividades académicas desde el formato presencial al confinamiento de las clases virtuales, de las que poco se ha estudiado sobre su efecto en la salud mental. Objetivo Determinar los niveles de depresión, ansiedad y estrés en estudiantes de medicina de México y Colombia durante la pandemia de COVID-19; además de comparar depresión, ansiedad y estrés por género, nivel educativo y país. Método Se realizó un estudio transversal con 426 estudiantes de medicina. Los datos se recopilaron mediante una encuesta en línea que contenía el cuestionario DASS-21. Resultados Las puntuaciones generales de depresión, ansiedad y estrés fueron 6.7 ± 1.2, 8.8 ± 1.2 y 5.6 ± 1.2, respectivamente. Las mujeres tuvieron puntajes generales significativamente más altos para depresión (.24-fold increase), ansiedad (.25-fold increase) y estrés (.40-fold increase). El riesgo de ansiedad y estrés por año escolar mostró que los años básicos se asociaron con puntajes más altos que los estudiantes en años los avanzados (.25 y .38-fold increase). Para las mujeres, cursar años básicos mostró un mayor riesgo de depresión en comparación con los estudiantes varones (.38-fold increase). Por último, los estudiantes mexicanos tuvieron un mayor riesgo de depresión y ansiedad (p ≤ .022 y p ≤ .004, respectivamente) pero no de estrés (p ≤ .402) en comparación con los estudiantes Colombianos. Discusión y conclusión Se observó ansiedad y depresión significativas en estudiantes de medicina mexicanos y colombianos. Los factores asociados a un mayor riesgo de depresión y ansiedad fueron; ser estudiante en años básicos además de ser mujer.

Phytochemical Compounds and Pharmacological Properties of Larrea tridentata.

For centuries, traditional medicine from plants (phytotherapy) was the only treatment for infectious and non-infectious diseases. Although it is still practiced in several countries with excellent therapeutic results, it is frequently underestimated because, unlike Western medicine, it is not based on an empirical scientific foundation. However, interest in the search for plant-based therapeutic resources has been stimulated by disciplines such as phytochemistry and the side effects of conventional pharmacological therapies. For example, Larrea tridentata is a perennial shrub used in traditional medicine in northern Mexico and the southern United States to treat infertility, rheumatism, arthritis, colds, diarrhea, skin problems, pain, inflammation and excess body weight. Scientific research has revealed its beneficial effects-antioxidant, antitumor, neuroprotective, regenerative, antibacterial, antiviral, antifungal, anthelmintic, antiprotozoal and insecticidal-although reports indicate that some compounds in Larrea tridentata may be hepatotoxic and nephrotoxic. Therefore, the aim of this review was to highlight the updates regarding phytochemical compounds and the pharmacological properties of Larrea tridentata.

Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. There are few data on the efficacy and safety in clinical practice of infliximab (CT-P13) in subcutaneous formulation (SC) for the treatment of patients with IBD. METHODS: Multicenter, prospective study of patients with IBD in clinical remission, who had their treatment changed from intravenous (IV) infliximab to SC. Two groups of patients were evaluated according to whether they were on IV infliximab treatment at standard or intensified doses before the switch. RESULTS: A total of 30 patients were on standard dosing and another 30 in intensified therapy. Treatment persistence in both groups at 6 months was greater than 95%. In both groups after the change, neither the biomarkers of inflammation nor the activity indices underwent significant changes at 3 and 6 months compared to the baseline value. Similarly, in both groups, infliximab trough levels showed a significant increase 3 and 6 months after the change to SC. No serious adverse events were registered. CONCLUSIONS: The CT-P13 SC brings a new anti-TNF era. Achieving much higher drug levels that are constant over time opens new paths to explore the management of patients with IBD: less immunogenicity, better perianal disease control and higher achievement of mucosal healing.

Effects of therapeutic exercises in patients with lung cancer. A scoping review.

INTRODUCTION: Lung cancer is one of the most common malignancies worldwide and the leading cause of cancer-related death. Smoking is one of the main risk factors associated with this cancer. Treatment will depend on the form of cancer and its stage, existing many therapeutic possibilities. In this regard, therapeutic exercise plays an important role in lung cancer care, as well as the pulmonary rehabilitation and respiratory physical therapy. PURPOSE: To review the current scientific literature about the effects of therapeutic exercise in lung cancer. METHOD: A search was carried out in CINAHL, MEDLINE, PubMed, Scopus y Web of Science using de terms "Exercise Therapy" and "Lung Neoplasms". 141 studies were obtained, but only 19 were selected by adjusting to the inclusion and exclusion criteria. 10 of them were randomized controlled trials with a Jadad score between 2 and 3. RESULTS: These works performed a large variety of interventions based on therapeutic exercise, classified in preoperative, postoperative, during treatment, post treatment and combination. Most focused on aerobic exercise, muscle strength and respiratory exercises. CONCLUSION: therapeutic exercise seems to be positive and obtain significant improvements in patients with lung cancer, regardless the moment of intervention and the type of exercise performed.

Feasibility of electronic brachytherapy in cervix cancer-A dosimetric comparison of different brachytherapy techniques.

INTRODUCTION: This study analyzes cases in which electronic brachytherapy (eBT) led to acceptable treatment plans in cervical cancer. Findings were compared with dosimetry values obtained in 192Ir-based treatments according to the high-risk clinical target volume (HR-CTV) and the disease stage. MATERIAL AND METHODS: We retrospectively analyzed 48 patients with cervical cancer from two centers. The patients were treated with 192Ir based on MRI. It was possible to use interstitial needles via an Utrecht-type applicator. Dosimetry was simulated using eBT and the parameters D90 and D98 (HR-CTV) and D2cc, D1cc, and D0.1cc (bladder, rectum, and sigmoid colon) were evaluated. The Mann-Whitney U test was used for comparison. The overall cohort of patients was analyzed, as were the sub-cohorts based on stage (FIGO stages I+IIA, IIB and III-IV). Finally, the dosimetry of the eBT plans was evaluated, and the plans obtained were classified as "good", "acceptable", or "poor". RESULTS: Statistically significant differences were found between the eBT and 192Ir plans for D98 (HR-CTV), D1cc and D0.1cc (bladder), and D1cc and D0.1cc (sigmoid colon). A total of 31 cases (64.6%) were considered good, seven (14.6%) were considered acceptable, and 10 (20.8%) were considered poor. For volumes <30 cc, all the plans were good or acceptable; for volumes >30 cc, 54.3% were good, and 71.4% were good or acceptable. By stage, eBT plans for patients with stage IB-IIA disease were good in 100%, whereas those for patients with stage IIB were good in 70.6% and III-IV disease were good in 50%. CONCLUSIONS: eBT provides appropriate dosimetry for treatment of cervical cancer in selected cases.

Antibacterial Potential of Caesalpinia coriaria (Jacq) Willd Fruit against Aeromonas spp. of Aquaculture Importance.

Aquaculture is an important source of food and livelihood for hundreds of millions of people around the world, however, aquaculture systems are affected by different factors, among them the appearance of resistant or multiresistant bacteria to antimicrobials. The secondary metabolites of plants have been proposed as alternatives for the treatment of these bacteria. The aim of the present study was to determine the antibacterial activity of Caesalpinia coriaria fruit hydroalcoholic extract and gallic acid over Aeromonas hydrophila, Aeromonas veronii,  and Aeromonas dhakensis to identify new molecules for the treatment of diseases caused by Aeromonas spp. The C. coriaria fruit hydroalcoholic extract (HECc) was obtained by hydroalcoholic maceration and subjected to bipartition with ethyl acetate and water to obtain an aqueous fraction (Ac-FrCc) and an organic fraction (Ac-FrEtCc); gallic acid was purchased commercially. The Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), MBC/MIC ratio, and cytotoxicity of HECc, its fractions, and gallic acid were determined. The results indicate that HECc fractions (Ac-FrCc and Ac-FrEtCc) and gallic acid have bactericidal activity against A. hydrophila and A. dhakensis, but only gallic acid showed bactericidal activity against A. veronii. The HECc and Ac-FrCc showed no toxicity, Ac-FrEtCc showed low toxicity, and gallic acid showed medium toxicity. The HECc, Ac-FrCc, and Ac-FrEtCc may be alternatives for the treatment of diseases caused by the genus Aeromonas, however, in vivo assays are necessary to corroborate these results.

Clinical Characteristics of Juvenile Idiopathic Inflammatory Myopathy and Comparison With Adult Patients: Analysis From a Multicentric Cohort in Spain.

METHODS: This study reviewed the medical records of patients from the REMICAM cohort, a multicentric longitudinal study carried out in patients with IIM, followed up between 1980 and 2014 in 12 hospitals in Madrid, Spain. Patients with definite or probable JPM, JDM, adult DM, and adult PM according to the modified Bohan and Peter criteria were selected. We compared the characteristics between JDM and JPM, and between JIIM and adult IIM. RESULTS: Eighty-six juvenile patients (75 JDMs and 11 JPMs) and 283 adult patients (133 DMs and 150 PMs) were included. Compared with patients with JDM, patients with JPM were older at diagnosis, had more fever and arthritis, and were less frequently treated with disease-modifying antirheumatic drugs (these differences were not statistically significant). Compared with patients with adult DM, those with JDM presented more frequently with calcinosis (33.8% vs 6.9%, p < 0.0001) and had less severe infections (4.3% vs 23.4%, p < 0.0001), malignancies (1.3% vs 25.6%, p < 0.0001), and mortality (3.5% vs 33%, p < 0.0001). Patients with JDM were treated less frequently with azathioprine (10.8% vs 44.7%, p < 0.0001). CONCLUSIONS: Our findings confirm that JIIMs are a heterogeneous group of diseases with relevant differences compared with adult IIMs.

Scleredema diabeticorum in a patient: un uncommon etiology of restrictive lung pattern Escleredema diabeticorum en un paciente: una etiología infrecuente de patrón restrictivo pulmonar.

Scleredema adultorum of Buschke is a rare skin disease characterized by skin thickening and tightening typically at the neck and the upper part of the body. This thickening results from increased mucin deposition in the reticular dermis. Three variants are recognized. Scleredema diabeticorum is one subtype associated with diabetes mellitus. We report a man with a history of poorly controlled diabetes presenting with extensive scleredema adultorum of the trunk in a "cuirasse" pattern associated with restrictive lung disease. Cutaneous ultrasonography revealed a marked thickening of the dermis as well as various echogenic spots in the dermis. Cutaneous hardness secondary to scleredema may cause limited mobility. Therefore, respiratory manifestations may be associated and assessed, mainly in cases of extensive scleredema involving trunk and shoulders. Moreover, cutaneous ultrasonography may be useful to monitor the evolution of scleredema and confirm the diagnosis.

Prognostic and Clinicopathological Significance of CCND1/Cyclin D1 Upregulation in Melanomas: A Systematic Review and Comprehensive Meta-Analysis.

Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23-3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40-0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01-2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification.

Lupus miliaris disseminatus faciei with complete response to isotretinoin.

Lupus miliaris disseminatus faciei is an uncommon type of granulomatous rosacea characterized by a papular eruption in the central regions of the face. A 43-year-old woman presented with an asymptomatic papular eruption on the face that had developed over a period of five months. Physical examination revealed multiple, small, reddish-brown papules, distributed symmetrically on the central area of the face. A biopsy was taken, showing dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. No foreign bodies were found in granulomas and no mycobacterial or fungal components were detected. On the basis of these findings, the diagnosis of lupus miliaris disseminatus faciei was made. The patient was given oral isotretinoin 20mg/day with initial slow response. After 6 months' treatment the lesions completely disappeared. Many authors consider this entity to be a variant of granulomatous rosacea. It is a chronic condition that primarily affects young adults. Treatment is usually unsatisfactory. Therapies with corticosterois, tetracyclines, retinoids, clofazimine or topical tacrolimus have been described but there is a lack of controlled studies and convincing results. Our success with a 6-month course of low dose isotretinoin suggests consideration of a longer trial prior to abandoning this as treatment.

Worldwide prevalence of oral lichen planus: A systematic review and meta-analysis.

The objective was to assess the global oral lichen planus prevalence. We searched PubMed, EMBASE, Web of Science, and Scopus for studies published before September 2019. We evaluated the quality of studies and carried out several meta-analyses. The global pooled prevalence was 1.01%, with a marked geographical difference (p < .001). The highest prevalence was reported from Europe (1.43%) and the lowest in India (0.49%), where tobacco-associated keratosis appears to mask oral lichen planus resulting in attenuation of its prevalence. From the age of 40 years, the prevalence increases significantly and progressively (OR = 3.43, 95% CI = 2.48-4.73, p < .001). Studies that define diagnostic criteria report a higher prevalence (1.31% vs. 0.70%, p = .03), although the application of the WHO criteria (year 1978-2007) does not increase the ability to diagnose the disease compared with other criteria (p = .11). The studies performed by oral medicine/oral pathology specialists report significantly higher prevalence (1.80%) than dentists (0.61%) and dermatologists (0.33%; p < .001). In conclusion, we propose that reliable diagnostic criteria should be defined, which should include a set of essential criteria including the presence of white reticular lesions in any location of the oral mucosa. The impact of histopathological confirmation with defined diagnostic criteria must be researched in the future, although its main use should be to determine the presence or absence of epithelial dysplasia. The necessity to improve the knowledge of oral lichen planus among dentists and dermatologists through continuing education is apparent in the results of this meta-analysis.

Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective immunohistochemistry study.

OBJECTIVE: To evaluate the relation between PD-L1 expression in oral cavity squamous cell carcinomas and clinicopathological features as well as survival outcomes. METHODS: A retrospective immunohistochemical study was carried out on 55 archived tumours from 55 patients. Tumours were stained for PD-L1 and scored by the proportion of tumour cells with positive membranous staining. PD-L1 scores were compared to the patient's clinicopathological characteristics for any significant associations. Kaplan-Meier curves were constructed for PD-L1 positive and negative tumours to investigate any advantage to survival. RESULTS: Positive PD-L1 staining was found in 58% of tumours and was significantly more likely in non-smokers, non-drinkers and in tongue squamous cell carcinomas. Increased PD-L1 was also associated with increased lymphocyte infiltration as well as PD-L1 staining in lymphocytes and the epithelium adjacent to tumour invasion. No survival benefit was seen from PD-L1 expression in tumour cells. CONCLUSIONS: PD-L1 expression is more common in non-smokers and non-drinkers, and its presence in the adjacent non-tumour epithelium suggests it may be involved in early oncogenesis.

Single-Molecule Conductance of 1,4-Azaborine Derivatives as Models of BN-doped PAHs.

The single-molecule conductance of a series of BN-acene-like derivatives has been measured by using scanning tunneling break-junction techniques. A strategic design of the target molecules has allowed us to include azaborine units in positions that unambiguously ensure electron transport through both heteroatoms, which is relevant for the development of customized BN-doped nanographenes. We show that the conductance of the anthracene azaborine derivative is comparable to that of the pristine all-carbon anthracene compound. Notably, this heteroatom substitution has also allowed us to perform similar measurements on the corresponding pentacene-like compound, which is found to have a similar conductance, thus evidencing that B-N doping could also be used to stabilize and characterize larger acenes for molecular electronics applications. Our conclusions are supported by state-of-the-art transport calculations.

Psoriasis pustulosa anular / Annular pustular psoriasis

No disponible

Methrotexate Treatment Inmunomodulates Abnormal Cytokine Expression by T CD4 Lymphocytes Present in DMARD-Naïve Rheumatoid Arthritis Patients.

CD4+T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-naïve RA patients, we investigated the pattern of IFNγ, IL-4 and IL-17A expression by naïve (TN), central (TCM), effector memory (TEM) and effector (TE) CD4+ subsets; their STAT-1, STAT-6 and STAT-3 transcription factors phosphorylation, and the circulating levels of IFNγ, IL-4 and IL-17. We also studied the RA patients after 3 and 6 months of MTX treatment and according their clinical response. CD4+T-lymphocyte subsets and cytokine expression were measured using flow cytometry. New-onset DMARD-naïve RA patients showed a significant expansion of IL-17A+, IFNγ+ and IL-17A+IFNγ+ CD4+T-lymphocyte subsets and increased intracellular STAT-1 and STAT-3 phosphorylation. Under basal conditions, nonresponder patients showed increased numbers of circulating IL-17A producing TN and TMC CD4+T-lymphocytes and IFNγ producing TN, TCM, TEM CD4+T-lymphocytes with respect to responders. After 6 months, the numbers of CD4+IL-17A+TN remained significantly increased in nonresponders. In conclusion, CD4+T-lymphocytes in new-onset DMARD-naïve RA patients show IL-17A and IFNγ abnormalities in TN, indicating their relevant role in early disease pathogenesis. Different patterns of CD4+ modulation are identified in MTX responders and nonresponders.

Prognostic and Clinicopathological Significance of FADD Upregulation in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Fas-associated death domain (FADD) upregulation, i.e., gene amplification, protein phosphorylation and/or overexpression, has shown promising prognostic implications in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aims to evaluate the clinicopathological and prognostic significance of FADD upregulation in HNSCC. We searched studies published before February 2020 through PubMed, Embase, Web of Science, Scopus and Google Scholar. We evaluated the quality of the studies included using the QUIPS tool. The impact of FADD upregulation on survival and clinicopathological variables was meta-analysed. We explored heterogeneity and their sources, conducted sensitivity analyses and investigated small-study effects. Thirteen studies (1,923 patients) met inclusion criteria. FADD immunohistochemical overexpression was statistically associated with worse overall survival (hazard ratio [HR] = 1.52, 95% confidence intervals [CI] = 1.28-1.81, p < 0.001), disease-specific survival (HR = 2.52, 95% CI = 1.61-3.96, p < 0.001), disease-free survival (HR = 1.67, 95% CI=1.29-2.15, p < 0.001), higher clinical stage (odds ratio [OR] = 1.72, 95% CI = 1.17-2.51, p = 0.005) and a large magnitude of effect with N+ status (OR = 2.36, 95% CI = 1.85-3.00, p < 0.001). FADD phosphorylation in ser-194 demonstrated no prognostic value, while no conclusive results can be drawn for FADD gene amplification. In conclusion, our findings indicate that immunohistochemical assessment of FADD overexpression could be incorporated into the prognostic evaluation of HNSCC.