Paradoxical Embolism in Juveniles and Young Adults With Severe-to-Profound Sudden Sensorineural Hearing Loss.

Objective: Paradoxical embolism from right-to-left shunting is a common cause of cryptogenic stroke in the young. Circulatory ischemia of the cochlea is closely connected with severe-to-profound sudden sensorineural hearing loss. This study aimed to explore the role of paradoxical embolism in severe-to-profound sudden sensorineural hearing loss in juveniles and young adults. Methods: From August 2021 to September 2022, consecutive outpatients under 35 years of age with severe-to-profound sudden hearing loss were included in the study. Routine auditory electrophysiological testing and contrast transcranial Doppler ultrasonography (c-TCD) were conducted, and the results were retrospectively analyzed. Results: Seven patients (age: 19.4 ± 6.5 years) were enrolled, including 5 juveniles and 2 young adults. Three patients had severe deafness, and 4 patients had profound deafness. Right-to-left shunting was detected in all patients through c-TCD. Patent foramen ovale was found in 2 patients while pulmonary arteriovenous fistula was found in 1 patient through contrast transthoracic echocardiography or cardiac catheterization. No patients had precipitating factors for sudden sensorineural hearing loss, and none had abnormalities on head magnetic resonance imaging. Six patients underwent whole-exome sequencing, and no known deafness gene variant was detected. After standard treatment for 1 month, 2, 3, and 2 patients had complete, slight, and no hearing recovery, respectively. Conclusions: Paradoxical embolism is a possible cause of severe-to-profound sudden sensorineural hearing loss in juveniles and young adults. In young patients, c-TCD is an effective screening tool to detect right-to-left shunting, while contrast transthoracic echocardiography is a complementary examination to c-TCD.

The Bioavailability of Drugs-The Current State of Knowledge.

Drug bioavailability is a crucial aspect of pharmacology, affecting the effectiveness of drug therapy. Understanding how drugs are absorbed, distributed, metabolized, and eliminated in patients' bodies is essential to ensure proper and safe treatment. This publication aims to highlight the relevance of drug bioavailability research and its importance in therapy. In addition to biochemical activity, bioavailability also plays a critical role in achieving the desired therapeutic effects. This may seem obvious, but it is worth noting that a drug can only produce the expected effect if the proper level of concentration can be achieved at the desired point in a patient's body. Given the differences between patients, drug dosages, and administration forms, understanding and controlling bioavailability has become a priority in pharmacology. This publication discusses the basic concepts of bioavailability and the factors affecting it. We also looked at various methods of assessing bioavailability, both in the laboratory and in the clinic. Notably, the introduction of new technologies and tools in this field is vital to achieve advances in drug bioavailability research. This publication also discusses cases of drugs with poorly described bioavailability, providing a deeper understanding of the complex challenges they pose to medical researchers and practitioners. Simultaneously, the article focuses on the perspectives and trends that may shape the future of research regarding bioavailability, which is crucial to the development of modern pharmacology and drug therapy. In this context, the publication offers an essential, meaningful contribution toward understanding and highlighting bioavailability's role in reliable patient treatment. The text also identifies areas that require further research and exploration.

Repetitive transcranial magnetic stimulation combined with olanzapine and amisulpride for treatment-refractory schizophrenia.

BACKGROUND: Treatment-refractory schizophrenia (TRS), accounting for approximately 30% of all schizophrenia cases, has poor treatment response and prognosis despite treatment with antipsychotic drugs. AIM: To analyze the therapeutic effectiveness of repetitive transcranial magnetic stimulation (rTMS) combined with olanzapine (OLZ) and amisulpride (AMI) for TRS and its influence on the patient's cognitive function. METHODS: This study enrolled 114 TRS patients who received treatment at the First Affiliated Hospital of Zhengzhou University between July 2019 and July 2022. In addition to the basic OLZ + AMI therapy, 54 cases of the control group (Con group) received modified electroconvulsive therapy, while 60 cases of the research group (Res group) received rTMS. Data on therapeutic effectiveness, safety (incidence of drowsiness, headache, nausea, vomiting, or memory impairment), Positive and Negative Symptom Scale, Montreal Cognitive Assessment Scale, and Schizophrenia Quality of Life Scale were collected from both cohorts for comparative analyses. RESULTS: The Res group elicited a higher overall response rate and better safety profile when compared with the Con group. Additionally, a significant reduction was observed in the post-treatment Positive and Negative Symptom Scale and Schizophrenia Quality of Life Scale scores of the Res group, presenting lower scores than those of the Con group. Furthermore, a significant increase in the Montreal Cognitive Assessment Scale score was reported in the Res group, with higher scores than those of the Con group. CONCLUSION: The treatment of TRS with rTMS and OLZ + AMI is effective and safe. Moreover, it can alleviate the patients' mental symptoms, improve their cognitive function and quality of life, and has a high clinical application value.

Therapeutic Effectiveness of Interferon-α2b against COVID-19 with Community-Acquired Pneumonia: The Ukrainian Experience.

Despite several targeted antiviral drugs against SARS-CoV-2 currently being available, the application of type I interferons (IFNs) still deserves attention as an alternative antiviral strategy. This study aimed to assess the therapeutic effectiveness of IFN-α in hospitalized patients with COVID-19-associated pneumonia. The prospective cohort study included 130 adult patients with coronavirus disease (COVID-19). A dose of 80,000 IU of IFN-α2b was administered daily intranasally for 10 days. Adding IFN-α2b to standard therapy reduces the length of the hospital stay by 3 days (p < 0.001). The level of CT-diagnosed lung injuries was reduced from 35% to 15% (p = 0.011) and CT injuries decreased from 50% to 15% (p = 0.017) by discharge. In the group of patients receiving IFN-α2b, the SpO2 index before and after treatment increased from 94 (92-96, Q1-Q3) to 96 (96-98, Q1-Q3) (p < 0.001), while the percentage of patients with normal saturation increased (from 33.9% to 74.6%, p < 0.05), but the level of SpO2 decreased in the low (from 52.5% to 16.9%) and very low (from 13.6% to 8.5%) categories. The addition of IFN-α2b to standard therapy has a positive effect on the course of severe COVID-19.

Therapeutic Effectiveness of Sesame Preparations and its Bioactive Ingredients in Management of Cardiometabolic Syndrome in Diabetes Mellitus: A Systematic Review.

AIM: This systematic review aimed to appraise and recapitulate all research investigations to elucidate the effects of Sesamum indicum preparations on managing the cardiometabolic syndrome of Diabetes mellitus (DM) and metabolic syndrome (MetS). METHODS: A systematic review was carried out in a Cochrane fashion and in compliance with the PRISMA checklist using the published academic works in PubMed/MEDLINE, WOS, SCOPUS, and EMBASE databases that were searched up to June 2021. Abstracts that met PICO criteria for qualitative studies were duplicate reviewed for data extraction to assess the quality and details of the study. RESULTS: Sesamum indicum preparations and its bioactive lignans, such as sesamin, sesamol, and pinoresinol, were found to possess anti-hyperglycemic, anti-hyperlipidemia, anti-inflammatory, antioxidative, anti-hypertensive, cardioprotective, and hepatoprotective effects both in patients with T2DM as well as in experimental animal models with T1DM and MetS. The incorporation of sesame oil as a natural adjuvant can be effective in improving vascular reactivity and aortic permeability, reproductive parameters, and diabetic nephropathy, as well as modification of anthropometry indices. Therefore, sesame oil and bioactive lignans as combination therapy with drugs can exhibit synergistic effects and provide a favorable preference in clinical settings. CONCLUSION: Sesame oil and lignans present in it act in a dose-dependent manner. The best dosage to improve risk biomarkers of patients with T2DM and MetS is 30-35 ml daily of sesame oil or inclusion of sesame oil in daily dietary patterns up to 30% of total energy for 8-12 weeks and/or 200 mg daily of sesamin supplementation for eight weeks.

First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency.

OBJECTIVE: To evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China. METHODS: Our study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency. RESULTS: Among the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP. CONCLUSION: The combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.

MicroRNAs as Predictors of Lung-Cancer Resistance and Sensitivity to Cisplatin.

BACKGROUND: Platinum-based chemotherapy, cisplatin (DDP) specifically, is the main strategy for treating lung cancer (LC). However, currently, there is a lack of predictive drug-resistance markers, and there is increased interest in the development of a reliable and sensitive panels of markers for DDP chemotherapy-effectiveness prediction. MicroRNAs represent a perspective pool of markers for chemotherapy effectiveness. OBJECTIVES: Data on miRNAs associated with LC DDP chemotherapy response are summarized and analyzed. MATERIALS AND METHODS: A comprehensive review of the data in the literature and an analysis of bioinformatics resources were performed. The gene targets of miRNAs, as well as their reciprocal relationships with miRNAs, were studied using several databases. RESULTS AND DISCUSSION: The complex analysis of bioinformatics resources and the literature indicated that the expressions of 12 miRNAs have a high predictive potential for LC DDP chemotherapy responses. The obtained information was discussed from the point of view of the main mechanisms of LC chemoresistance. CONCLUSIONS: An overview of the published data and bioinformatics resources, with respect to the predictive microRNA markers of chemotherapy response, is presented in this review. The selected microRNAs and gene panel have a high potential for predicting LC DDP sensitiveness or DDP resistance as well as for the development of a DDP co-therapy.

Real-world studies: bridging the gap between trial-assessed efficacy and routine care.

Even though randomized controlled clinical trials (RCTs) have been accepted as the gold standard for official assessment of novel interventions, there is a substantial gap between the efficacy observed in RCTs and the impact on clinical practice and in terms of patient benefit. While real-world studies (RWS) are emerging to confer valuable complementing evidence in this regard and beyond, the evolving role of RWS is yet to be agreed. This article delineates an updated profile of RWS covering effectiveness verification, rare adverse effects discovery, indication repurposing, to name a few. RWS tends not only to improve the efficiency of clinical investigations for regulatory approval, but also optimizes the whole-life cycle evaluation of biomedical/pharmaceutical products.

Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis.

BACKGROUND: Some depressed patients receive acupuncture as an adjunct to their conventional medications. OBJECTIVE: This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants. SEARCH STRATEGY: English and Chinese databases were searched for randomized controlled trials (RCTs) published until December 1, 2021. INCLUSION CRITERIA: RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone. DATA EXTRACTION AND ANALYSIS: Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran's Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence in the included studies. RESULTS: This review included 16 studies (with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17 (HAMD-17) scores (standard mean difference [SMD] -0.44, 95% confidence interval [CI] -0.55 to -0.33, P < 0.01; I2 = 14%), Self-rating Depression Scale (SDS) scores (SMD -0.53, 95% CI -0.84 to -0.23, P < 0.01; I2 = 79%), and the Side Effect Rating Scale (SERS) scores (SMD -1.11, 95% CI -1.56 to -0.66, P < 0.01; I2 = 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores (SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01; I2 = 15%), decreased the number of participants who increased their antidepressant dosages (relative risk [RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01; I2 = 0%), and resulted in significantly higher remission rates (RR 1.52, 95% CI 1.26 to 1.83, P < 0.01; I2 = 0%) and treatment responses (RR 1.35, 95% CI 1.24 to 1.47, P < 0.01; I2 = 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality. CONCLUSION: Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control. SYSTEMATIC REVIEW REGISTRATION: INPLASY202150008.

Research Progress of Biomarkers for Immune Checkpoint Inhibitors on Digestive System Cancers.

Immunotherapy represented by immune checkpoint inhibitors has gradually entered a new era of precision medicine. In view of the limited clinical benefits of immunotherapy in patients with digestive system cancers, as well as the side-effects and high treatment costs, development of biomarkers to predict the efficacy of immune therapy is a key imperative. In this article, we review the available evidence of the value of microsatellite mismatch repair, tumor mutation burden, specific mutated genes or pathways, PD-L1 expression, immune-related adverse reactions, blood biomarkers, and patient-related biomarkers in predicting the efficacy of immunotherapy against digestive system cancers. Establishment of dynamic personalized prediction models based on multiple biomarkers is a promising area for future research.

Analysis of therapeutic effectiveness and adverse effects of long-term corticosteroids among leprosy patients with reactions: A retrospective cohort study.

Objectives: Main therapy for leprosy reactions is 12 weeks corticosteroids according to World Health Organization recommendations, but recovery cannot be achieved and recurrence occurs. Long duration of administration was thought to provide better clinical improvement. Evidence of the efficacy of corticosteroids in leprosy reactions is still lacking, and optimal dose and duration of therapy vary, while the need for long-term high-dose corticosteroids makes it difficult to avoid adverse effects. Methods: This is a retrospective cohort study analyzing the difference between therapeutic effectiveness and adverse effects of 12 weeks and >12 weeks corticosteroids, involving all new leprosy patients without age restriction, at Cipto Mangunkusumo Hospital and Cakung Community Health Center in Indonesia during 1 January 2015-31 December 2017. Secondary data were collected from medical records, and observations carried out until December 2018. Therapeutic effectiveness was assessed from clinical improvement to corticosteroids discontinuation, without 3 months recurrence after first cycle was completed. Adverse effects were assessed by all corticosteroids-related side effects. Results: Of 195 patients, 57 (29.2%) used 12 weeks corticosteroids, and 138 (70.8%) for >12 weeks. Effectiveness occurred in 38 (66.7%) of 12 weeks group and 106 (76.8%) of >12 weeks group (relative risk = 0.604, 95% confidence interval = 0.307-1.189, p = 0.143). Of 145 patients, adverse effects occurred in 12 (31.6%) of 12 weeks group and 70 (65.4%) of >12 weeks group (relative risk = 0.244, 95% confidence interval = 0.111-0.538, p < 0.001). Of 171 adverse effects, 37.4% were mild such as dyspepsia, skin disorders, and lipodystrophy, while 62.6% were severe in the form of neuropsychiatric disorders, eye disorders, cardiovascular disease, gastrointestinal bleeding, metabolic-hormonal abnormalities, and reactivation of infections. Conclusion: There is no effectiveness difference in the form of clinical improvement without 3 months recurrence, between 12 weeks and >12 weeks corticosteroid, while longer administration causes 4 times more events.

The miRNAs involved in prostate cancer chemotherapy response as chemoresistance and chemosensitivity predictors.

BACKGROUND: Reliable molecular markers that allow the rational prescription of an effective chemotherapy type for each prostate cancer patient are still needed. Since microRNAs expression is associated with the response to different types of prostate cancer therapy, microRNAs represent a pool of perspective markers of therapy effectiveness comprising chemotherapy. OBJECTIVES: The available data on microRNAs associated with chemotherapy response (resistance and sensitivity) are summarized and analyzed in the article. MATERIALS AND METHODS: A review of the published data, as well as their analysis by current bioinformatics resources, was conducted. The molecular targets of microRNAs, as well as the reciprocal relationships between the microRNAs and their targets, were studied using the DIANA, STRING, and TransmiR databases. Special attention was dedicated to the mechanisms of prostate cancer chemoresistance development. RESULTS AND DISCUSSION: The combined analysis of bioinformatics resources and the available literature indicated that the expression of eight microRNAs that are associated with different responses to chemotherapy have a high potential for the prediction of the prostate cancer chemotherapy response, as found in the experiments and confirmed by the functions of regulated genes. CONCLUSION: An overview on the published data and bioinformatics resources, with respect to predictive microRNA markers of chemotherapy response, is presented in this review. The selected microRNA and gene panel has a high potential for predicting the chemosensitivity or chemoresistance of prostate cancer and could represent a set of markers for subsequent study using samples of cell-free microRNAs from different patient groups.

Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Some depressed patients receive acupuncture as an adjunct to their conventional medications.@*OBJECTIVE@#This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.@*SEARCH STRATEGY@#English and Chinese databases were searched for randomized controlled trials (RCTs) published until December 1, 2021.@*INCLUSION CRITERIA@#RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.@*DATA EXTRACTION AND ANALYSIS@#Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran's Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence in the included studies.@*RESULTS@#This review included 16 studies (with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17 (HAMD-17) scores (standard mean difference [SMD] -0.44, 95% confidence interval [CI] -0.55 to -0.33, P < 0.01; I2 = 14%), Self-rating Depression Scale (SDS) scores (SMD -0.53, 95% CI -0.84 to -0.23, P < 0.01; I2 = 79%), and the Side Effect Rating Scale (SERS) scores (SMD -1.11, 95% CI -1.56 to -0.66, P < 0.01; I2 = 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores (SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01; I2 = 15%), decreased the number of participants who increased their antidepressant dosages (relative risk [RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01; I2 = 0%), and resulted in significantly higher remission rates (RR 1.52, 95% CI 1.26 to 1.83, P < 0.01; I2 = 0%) and treatment responses (RR 1.35, 95% CI 1.24 to 1.47, P < 0.01; I2 = 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.@*CONCLUSION@#Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.@*SYSTEMATIC REVIEW REGISTRATION@#INPLASY202150008.

Terapias físicas en pacientes con trastornos de la articulación temporomandibular / Physical therapies in patients with temporomandibular joint disorders

RESUMEN Introducción: Se denomina trastorno temporomandibular al conjunto de condiciones musculoesqueléticas que afectan la articulación temporomandibular, los músculos de la masticación y las estructuras anatómicas adyacentes. Objetivo: Evaluar la efectividad de las terapias físicas en pacientes con trastornos de la articulación temporomandibular. Métodos: Se efectuó una intervención terapéutica en la Clínica Estomatológica Provincial Docente Mártires del Moncada de Santiago de Cuba, desde junio de 2016 hasta febrero de 2020. La muestra quedó conformada por 264 pacientes distribuidos en 4 grupos con 66 integrantes cada uno, a quienes se les aplicaron diferentes terapias físicas, tales como ultrasonido, laserterapia, magnetoterapia y técnica de estimulación eléctrica transcutánea, respectivamente. Se analizaron las siguientes variables: edad, grado de trastorno de la articulación temporomandibular y efectividad terapéutica. Se empleó el porcentaje como medida de resumen y el estadígrafo de Ji al cuadrado con un nivel de significación de 0,05. Resultados: Predominó el sexo femenino en todas las terapias aplicadas con más de 75,0 % y el grupo etario de 40 - 49 años. Al finalizar el tratamiento se observó que en los grupos donde se empleó ultrasonido, láser y magneto, la respuesta fue efectiva en más de 90,0 % de los pacientes, con primacía del primero (96,6 %); sin embargo, en el grupo donde se utilizó la técnica de estimulación eléctrica transcutánea solo se logró en 89,4 % de los afectados. Conclusiones: La ultrasonoterapia fue más efectiva en pacientes con trastornos de la articulación temporomandibular.

ABSTRACT Introduction: A temporomandibular disorder is a group of musculoskeletal conditions that affect the temporomandibular joint, the mastication muscles and the adjacent anatomical structures. Objective: To evaluate the effectiveness of the physical therapies in patients with temporomandibular joint disorders. Methods: A therapeutic intervention was carried out in Mártires del Moncada Teaching Provincial Stomatological Clinic from Santiago de Cuba, from June, 2016 to February, 2020. The sample was formed by 264 patients distributed in 4 groups with 66 members each one, to whom different physical therapies were applied, such as ultrasound, laser therapy, magnetotherapy and technique of transcutaneous electric stimulation, respectively. The following variables were analyzed: age, grade of dysfunction of the temporomandibular joint and therapeutic effectiveness. The percentage as summary measure and the chi-squared test were used with a significance level of 0.05. Results: There was a prevalence of the female sex in all the therapies applied with more than 75.0 % and the 40 - 49 age group. When concluding the treatment it was observed that in the groups where ultrasound, laser and magneto was used, the response was effective in more than 90.0 % of the patients, with primacy of the first one (96.6 %); however, in the group where the technique of transcutaneous electric stimulation was used it was just achieved in 89.4 % of the affected patients. Conclusions: The ultrasonotherapy was more effective in patients with temporomandibular joint disorders.

[The importance of patient reported outcome measures in Pompe disease]. / A betegek által riportált kimeneti mutatók jelentosége Pompe-kórban.

BACKGROUND AND PURPOSE: In recent decades it has become increasingly important to involve patients in their diagnostic and treatment process to improve treatment outcomes and optimize compliance. By their involvement, patients can become active participants in therapeutic developments and their observations can be utilized in determining the unmet needs and priorities in clinical research. This is especially true in rare diseases such as Pompe disease. Pompe disease is a genetically determined lysosomal storage disease featuring severe limb-girdle and axial muscle weakness accompanied with respiratory insufficiency, in which enzyme replacement therapy (ERT) now has been available for 15 years. METHODS: In our present study, patient reported outcome measures (PROMs) for individuals affected with Pompe disease were developed which included questionnaires assessing general quality of life (EuroQoL, EQ-5D, SF36), daily activities and motor performance (Fatigue Severity Score, R-PAct-Scale, Rotterdam and Bartel disability scale). Data were collected for three subsequent years. The PROM questionnaires were a good complement to the physician-recorded condition assessment, and on certain aspects only PROMs provided information (e.g. fatigue in excess of patients' objective muscle weakness; deteriorating social activities despite stagnant physical abilities; significant individual differences in certain domains). The psychological effects of disease burden were also reflected in PROMs. RESULTS: In addition to medical examination and certain endpoints monitored by physicians, patient perspectives need to be taken into account when assessing the effectiveness of new, innovative treatments. With involvement of patients, information can be obtained that might remain uncovered during regular medical visits, although it is essential in determining the directions and priorities of clinical research. CONCLUSION: For all orphan medicines we emphasize to include patients in a compulsory manner to obtain general and disease-specific multidimensional outcome measures and use them as a quality indicator to monitor treatment effectiveness.

MiRNAs and radical prostatectomy: Current data, bioinformatic analysis and utility as predictors of tumour relapse.

BACKGROUND: Studies of microRNAs (miRNAs) and genes have particular interest for cancer biology and medicine due to the discovery of new therapeutic targets and markers. These studies are extensively influenced by anticancer therapy, as miRNAs interfere with the therapy's efficacy in prostate cancer (PCa). OBJECTIVES: In this article, we summarise the available data on the influence of radical prostatectomy (RP) and biochemical recurrence on miRNA expression. MATERIALS AND METHODS: Molecular targets of these miRNAs, as well as the reciprocal relations between different miRNAs and their targets, were studied using the DIANA, STRING and TransmiR databases. Special attention was dedicated to the mechanisms of PCa development, miRNA, and associated genes as tumour development mediators. RESULTS AND DISCUSSION: Combined analysis of the databases and available literature indicates that expression of four miRNAs that are associated with prostate cancer relapse and alter their expression after RP, combined with genes that closely interact with selected miRNAs, has high potential for the prediction of PCa relapse after RP. PCa tissues and biofluids, both immediately after RP for diagnostics/prognostics and in long-term (relapse) monitoring, may be used as sources of these miRNAs. CONCLUSION: An overview of the usefulness of published data and bioinformatics resources looking for diagnostic markers and molecular targets is presented in this article. The selected miRNA and gene panels have good potential as prognostic and PCa relapse markers after RP and likely could also serve as markers for therapeutic efficiency on a broader scale.

miRNAs and radiotherapy response in prostate cancer.

BACKGROUND: Gaining insight into microRNAs (miRNAs) and genes that regulate the therapeutic response of cancer diseases in general and prostate cancer (PCa) in particular is an important issue in current molecular biomedicine and allows the discovery of predictive miRNA targets. OBJECTIVES: The aim of this study was to analyze the available data on the influence of radiotherapy (RT) on miRNA expression and on miRNA involved in radiotherapy response in PCa. MATERIALS AND METHODS: The data used in this review were extracted from research papers and the DIANA, STRING, and other databases with a special focus on the mechanisms of radiotherapy PCa response and the miRNA involved and associated genes. RESULTS AND DISCUSSION: A search for miRNA prognostic and therapeutic effectiveness markers should rely on both the data of recent experimental studies on the influence of RT on miRNA expression and miRNAs involved in regulation of radiosensitivity in PCa and on bioinformatics resources. miRNA panels and genes targeted by them and involved in radioresponse regulation highlighted by meta-analysis and cross-analysis of the data in the present review have. CONCLUSION: Selected miRNA and gene panel has good potential as prognostic and radiotherapy effectiveness markers for PCa and, moreover, as radiotherapy effectiveness markers in other types of cancer, as the proposed model is not specific to PCa, which opens up opportunities for the development of a universal diagnostic system (or several intersecting systems) for oncology radiotherapy in general.

The first investigation on differences in the effectiveness of mycophenolate mofetil and azathioprine antimetabolites determined in Polish patients treated for non-infectious uveitis.

INTRODUCTION: The non-infectious uveitis, a serious vision-threatening disease is the fourth most common cause of blindness in working population of the developed world. Various antimetabolites are applied in corticosteroid-sparing therapy also in Poland but their efficacy was not compared in our country. The aim of our study was to compare mycophenolate mofetil and azathioprine in terms of therapeutic effect of the antimetabolites in Polish patients with this disease. MATERIAL AND METHODS: The comparative, retrospective study included data of 61 patients admitted to Independent Public University Eye Hospital between January 2009 and January 2017, treated with antimetabolites for non-infectious uveitis. 31 patients received mycophenolate mofetil, 30 patients - azathioprine. In the assessment of corticosteroid-sparing efficacy, among others changes in visual acuity, the duration of the disease and therapy, incidence of ophthalmologic complications, adverse systemic side effects were determined. RESULTS: The corticosteroid-sparing therapy was more often effective, and an improvement of visual acuity more frequent in patients treated with mycophenolate mofetil than in these receiving azathioprine (84% patients vs. 60%, and 27% patients vs. 13%, respectively); these differences were statistically significant (p<0.05). CONCLUSIONS: Results of our study showing better therapeutic efficacy when applied mycophenolate mofetil seems promising approach for treatment of non-infectious posterior uveitis and panuveitis. In the first study, there was different duration of the disease before drug administration (10.5 years vs. 7.14 years in the azathioprine and mycophenolate mofetil therapy, respectively, p<0.05) and limited number of patients assessed, thus it is desirable to examine more Polish patients treated with the antimetabolites.