Principles Of Treatment Research Articles

VAT and Directors’ Fees: Can Directors Who Are Individuals Be Considered Taxable Persons?

In the aftermath of the ECJ’s decision in the TP (C-288/22) case, the author of this article argues that directors who are private persons can be taxable persons for VAT purposes. The author argues that this idea is a solution in line with the broadness inherent in the concept of taxable person and that directors can fulfil the requirements of “any person”, “economic activity” and of acting “independently”. In addition, the author stresses that depriving an individual of such a status may equate to hindering legal neutrality (or at least the principle of equal treatment), as well as affecting system neutrality. Furthermore, this article reveals the alignment of this position with economic reality. Lastly, it will signal some of the undesirable consequences of negating the taxable person status: from non-taxation and creation of opportunities for tax avoidance, to tax non-neutrality.

Vulvar cancer. The contribution of radiotherapy to the treatment of the disease

The aim of the study was to analyze and summarize the available literature data on the modern radiotherapy techniques, indications for radiotherapy (preoperative, radical, postoperative radiation therapy), treatment volumes at different disease stages, and principles of drug and accompanying therapy for patients with vulvar cancer. Material and Methods. The literature review was based on the clinical recommendations of the Ministry of Health of the Russian Federation and National Comprehensive Cancer Network (NCC N), as well as on the search of sources in PubMed and Cochrane Library systems. Literature sources and publications from 2005 to 2023 were included. Results. This contribution outlined the main indications for preoperative, postoperative and radical radiotherapy in patients with vulvar cancer, as well as the basic principles of drug treatment and correction of complications. Potential risk factors for postoperative disease recurrence were identified, the volumes of irradiation at each treatment mode were analyzed, and the feasibility of using brachytherapy in patients with vulvar cancer was discussed. Conclusion. To date, there are recommendations, guidelines for the management of patients with vulvar cancer, as well as clinical trial results. Understanding of the principles of prescribing treatment for vulvar cancer patients can improve local control, overall and recurrence-free survival, and the use of modern radiotherapy techniques will enshure an acceptable quality of life in these patients.

Oral antidiabetic therapy versus early insulinization on glycemic control in newly diagnosed type 2 diabetes patients: a retrospective matched cohort study

Our study aims to compare the efficacy of oral antidiabetic therapy to early insulinization on glycemic control among newly diagnosed type 2 diabetes patients in real-world clinical practice. A retrospective cohort study conducted at a medical center in Taiwan analyzed 1256 eligible patients from January 2007 to December 2017. Propensity score matching resulted in well-balanced groups of 94 patients each in the oral antidiabetic drug (OAD) and early insulinization cohorts. Glycemic outcomes were assessed in both groups. Patients exclusively using OAD showed consistently lower glycated hemoglobin (HbA1c) levels at 3, 12, 24, and 36 months compared to insulin users. At later periods, 77.7% of OAD users achieved glycemic control versus 64.9% of insulin users, with a marginally significant difference. Subgroup analyses suggested a trend favoring well-controlled diabetes in the OAD group, though not statistically significant. Our study finds oral antidiabetic therapy is not inferior to early insulinization for glycemic control in newly diagnosed type 2 diabetes patients, irrespective of initial HbA1c levels. This supports oral therapy as a rational treatment option, even in cases with elevated HbA1c at diagnosis.

Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations

BackgroundOX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we...

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Arthritis increases the risk of erectile dysfunction: Results from the NHANES 2001-2004.

This study assessed the association between erectile dysfunction (ED) and arthritis. Weighted logistic regression and subgroup analyses were used to investigate the association between arthritis incidence and ED among participants in the 2001-2004 National Health and Nutrition Examination Survey database. Among the participants, 27.8% and 18.5% had a self-reported history of ED and arthritis, respectively. ED was associated with arthritis (odds ratio [OR]=4.00; 95% confidence interval [CI]: 3.20-4.99; p<0.001], which remained significant after adjustment (OR=1.42, 95% CI: 1.00-1.96; p<0.001). Stratified by type of arthritis, after full adjustment, osteoarthritis remained significant (OR=1.11; 95% CI: 1.03-1.20; p=0.017), and rheumatoid arthritis (OR=1.03, 95% CI: 0.93-1.13; p= 0.5) and other arthritis (OR=1.04, 95% CI: 0.98-1.11; p=0.2) were not significantly correlated with ED. Multiple inference analyses confirmed the robustness of the results. Our study showed that arthritis was strongly associated with ED. There is an urgent need to raise awareness and conduct additional research on the reasons behind this association in order to implement more scientific and rational treatment programs for patients with ED and arthritis.

Interstitial lung disease: diagnosis and management principles

Interstitial lung disease (ILD) encompasses a diverse group of chronic, often progressive, parenchymal lung disorders with varying aetiologies. Advanced clinical practitioners (ACPs) increasingly play a crucial role in the multidisciplinary management of ILD patients across a variety of healthcare settings, enabling timely access to specialised expertise, co-ordinating multidisciplinary care and enhancing patient understanding. An awareness of the principles of diagnosis and management are key to support patient care, as ACPs will need to consider the type of ILD, and its trajectory and prognosis, with and without treatment. Most importantly, the views and health beliefs of the patient must take centre stage, with careful assessment and counselling required prior to commencing treatment. Multimorbidity is common and may impact on both symptoms and treatment tolerance. Considering the holistic needs of the patient is essential and a focus on quality of life should remain a priority. This review examines the nature of ILDs and summarises their treatment principles, with a specific focus on symptom management.

Analysis of YouTube-Based Therapeutic Content for Children with Cerebral Palsy.

Cerebral palsy (CP) causes movement and posture challenges due to central nervous system damage, requiring lifelong management. During the COVID-19 pandemic, there was limited access to facility-based treatments, which increased the demand for home-based therapies and digital resources. We analyzed the qualitative and quantitative aspects of YouTube videos focusing on CP therapy for children. A total of 95 videos were evaluated for content quality using the modified DISCERN (mDISCERN) tool and Global Quality Scale (GQS). The therapeutic program efficacy was assessed via the International Consensus on Therapeutic Exercise and Training (i-CONTENT) tool, Consensus on Therapeutic Exercise Training (CONTENT) scale, and Consensus on Exercise Reporting Template (CERT), and popularity was measured by the video power index (VPI). YouTube-based therapeutic videos for children with CP generally exhibit reliability in video content and effectiveness in therapeutic programming, and no correlations were found between video popularity and quality. However, the qualitative analysis reveals insufficient mention of uncertainty in the treatment principles within the video content as well as a lack of detailed treatment descriptions encompassing aspects such as intensity, frequency, timing, setting, outcome measurement during and post-treatment, and safety considerations within therapeutic programs. In particular, this tendency was consistent regardless of the uploader's expertise level and the classification of the neuromotor therapy type in contrast to that of the exercise type. YouTube-based content for CP children still has significant limitations in how substantive viewers, such as caregivers, can acquire tailored information and apply practical information to their exercise and treatment programs.

DNA Protective Assay and Some Biochemical Properties of Galium Species

Herbal-derived drugs prepared using various extracts obtained from different organs of plants that have been scientifically proven to be “medicinal” or directly from these plants are often used today as a method to prevent or treat diseases in humans and animals. This method, called phytotherapy, is a rational, evidence-based, and allopathic treatment method and deals with which active substance group is responsible for the biological effects. In this context, the phytotherapeutic effectiveness of Galium species, which are also used for medicinal purposes among the public, has been examined and proven in many studies. In this study, the biochemical efficacies of five different Galium species were measured and their antioxidant, antimicrobial, and DNA protective effects were tested. It was found that the tested Galium species showed remarkable biochemical efficacies. The results were also compared with the results of some other studies in the literature.

AUTOIMMUNE ENCEPHALITIS: DIAGNOSTIC AND TREATMENT APPROACH

Autoimmune encephalitis is a type of brain inflammation induced by an inappropriate immune response to a neuronal antigen, resulting in the generation of autoantibodies. Autoimmunity as important cause of encephalitis in recent years has not been much reported in Indonesia. Increased familiarity with autoimmune encephalitis among physician, not only neurologist, is extremely important for early detection. Prompt diagnosis and early immunotherapy leads to better prognosis in this potentially treatable disease, despite a long disease course. Autoimmune encephalitis is characterized by acute-subacute progressive neuropsychiatric symptoms with associated cognitive dysfunction, encephalopathy, psychiatric disorders, movement disorders and seizures, with anti-N-methyl-D-aspartate (NMDA) receptors encephalitis as the most common type. In addition to clinical features, further diagnostic investigations needed are brain magnetic resonance imaging (MRI), electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, and autoantibody testing. Challenges in establishing diagnosis include wide range of clinical symptoms, absence of abnormalities in brain MRI, unspecified EEG findings, negative antibody testing, and limited availability of antibody testing in Indonesia. This literature review discusses the recognition, diagnosis and principle of treatment of autoimmune encephalitis.

The latest IC3D classification of corneal dystrophies-Overview and changes of the 3rd edition

The International Committee on Classification of Corneal Dystrophies (IC3D) was founded in 2005 to address difficulties arising from the outdated nomenclature for corneal dystrophies (CD) and to correct misconceptions in the literature. For each of the 22CDs, aseparate template was created to represent the current clinical, pathological and genetic knowledge of the disease. In addition, each template contains representative clinical photographs as well as light and electron microscopic images and, if available, confocal microscopic and coherence tomographic images of the respective CD. After the first edition was published in 2008, the revised version followed in 2015. The third edition of the IC3D was published as open access in February 2024. The latest edition is intended to serve as areference work in everyday clinical practice and facilitate the diagnosis of CD, which might sometimes be difficult. This article provides an overview of the diagnostic and treatment principles of CD and presents the IC3D and its changes over time.

Management of Guillain–Barre Syndrome through Basti (Medicated Enema) and Composite Ayurveda Treatment: A Case Report

Abstract BACKGROUND: Guillain–Barre syndrome (GBS) is a condition characterized by polyradiculoneuropathy associated with an immune-mediated response. Conventional therapies such as intravenous immunoglobulins and plasma exchange have been used to manage this condition, but they often result in unpleasant clinical and electrophysiological outcomes. The present case report describes traditional Ayurveda treatments, specifically Basti (medicated enema) and composite Ayurveda treatment, used to manage GBS. This report aims to provide insights into the effectiveness of traditional Ayurvedic treatments in managing GBS. MATERIALS AND METHODS: In this case, the patient presented with complaints of tingling and numbness in the bilateral upper and lower limbs for 2 months, weakness in bilateral upper and lower limbs for 1 month, inability to stand and walk, pain in the lumbar region, intermittent constipation, and dysphagia since 1 month. The patient was diagnosed with Guillain–Barre syndrome based on clinical findings, electromyography, and nerve conduction velocity test (EMG-NCV). He received treatment from a private hospital, but his symptoms were aggravated, so he was referred to Government Ayurveda Hospital Nagpur for further clinical management. Plasma transfusion was done at PVT Hospital 15 days before. He was treated based on the treatment principles of Vatavyadhi Chikitsa, Vata Dosha Upkram, and Santarpan Chikitsa. The primary goals of the therapy were to nourish the bodily tissues (Santarpan) and pacify the Pitta Dosha (Pittaghna). RESULTS: The patient’s electromyography and nerve conduction velocity test (EMG-NCV) results showed acute demyelinating sensorimotor polyneuropathy involving both the upper limbs and lower limbs. Compared to before treatment, EMG-NCV studies showed definite improvement in compound motor action potential (CMAP) amplitudes more prominently in upper limbs after 4 months of therapy. The muscle power grade increased from 0 to 5, indicating a significant improvement. The bedridden patient can walk alone after the completion of treatment. CONCLUSION: This case study reveals that Ayurvedic treatment has the potential for significant recovery in GBS instances.

Treatment of Cardiac Neurosis based on the "Harmonizing and Regulating the Pivot" Approach

The incidence of cardiac neurosis is increasing year by year, and there is a trend of rejuvenation. The etiology and pathological mechanism of Western medicine are complex, and it is believed that it may be related to the environment, personality and psycho-neurological factors, etc. Clinical treatments are based on sedation, anti-anxiety and symptomatic treatments, and the efficacy of the treatments is not good. This paper is based on the theory of "Harmonizing and Regulating the Pivot" elaborates on the correlation between cardiac neurosis and the cardiac mechanism, analyses the mechanism and treatment of cardiac neurosis in Chinese medicine, and concludes that the mechanism of this disease is the pivotal folding of the pivotal depression, the evil guest pivotal micro-organisms, the qi and blood deficiency stagnation, the imbalance of yin and yang; the treatment principle is to regulate the pivot to reach the pivot depression, to dispel the evils and the pivot, the external transfer of the internal and the harmonization and regulating the qi and blood, and to harmonise yin and yang and pivot the holding of the cold and heat. It further improves the pathogenesis and treatment of cardiac neurosis and provides reference for clinical treatment.

CD74-AKT Axis Is a Potential Therapeutic Target in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) cells are often resistant to FAS (CD95)-mediated apoptosis, but the underlying molecular mechanism(s) is not fully understood yet. Notably, the expression of the type II transmembrane protein, CD74, is correlated with chemotherapy-resistant and more invasive forms of cancers via unknown mechanisms. Here, we analyzed gene expression pattern of cancer patients and/or patient-derived xenograft (PDX) models and found that mRNA and protein levels of CD74 are highly expressed in TNBC and correlated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) properties. Mechanistically, we found that AKT activation is likely critical for maintaining CD74 expression and protein stability to favor its oncogenic functions. Physiologically, epidermal growth factor (EGF) along with CD74 could activate AKT signaling, likely through binding of phosphorylated AKT (S473) to CD74, whereas inhibition of AKT could impair stability of CD74. We also revealed that CD74 binds to FAS and interferes with the intrinsic signaling of FAS-mediated apoptosis. As such, selective targeting of the CD74/FAS complex using the AKT inhibitor along with the CD74-derived peptide could synergistically restore and activate FAS-mediated apoptosis. Therefore, our approach of mobilizing apoptosis pathways likely provides a rationale for TNBC treatment by targeting the CD74/FAS and CD74-AKT axes.

Рідкісне спостереження одномоментного видалення гігантської крижово-куприкової тератоми з масивними пресакральним і зовнішнім компонентами та доопераційною ендоваскулярною оклюзією живлячих артерій пухлини в новонародженої дитини

Aim - to analyze and describe the experience of a one-moment removal of a giant sacrococcygeal teratoma (SCT), with massive presacral and external components (III type), and preoperative endovascular occlusion of the feeding arteries of the tumor, in a newborn, based on a clinical case. Clinical case. A unique clinical case of a giant SCT with massive presacral and external components and preoperative endovascular occlusion of the feeding arteries of the tumor in a newborn is presented. Features of perinatal support, preoperative endovascular occlusion of the feeding arteries of the SCT and surgical intervention are described, which are important elements of optimizing the treatment of children with this life-threatening pathology. Conclusions. In the diagnosis and treatment of SCT, a scientifically based, differentiated approach is necessary, which includes: early (up to 22 weeks of gestation) complex prenatal diagnosis for choosing rational tactics of pregnancy management, examination of the fetus, delivery by cesarean section, postnatal diagnosis, preoperative preparation and surgical treatment. The first described preoperative endovascular occlusion of the feeding arteries of the presacral and external components of the SCT provides tumor devascularization and minimization of intraoperative blood loss during one-moment resection of a highly vascularized giant tumor. Adequate assessment and rational conservative treatment of a severe complication of the early postoperative period - thrombosis of the infrarenal section of the aorta made it possible to eliminate the life-threatening complication and achieve complete recanalization of the thrombosed section of the aorta and restore full blood flow in the lower extremities. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting studies. No conflict of interests was declared by the authors.

Ascending colon cancer metastasized to the right testicle: a case report

BackgroundTesticular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient’s case of testicular metastasis from colon cancer.Case presentationWe report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography–computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma.ConclusionColon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.

Engage! a pilot study of a brief behavioural activation program to promote engagement and well-being in older adults.

Previous research has indicated the suitability of behavioural activation (BA) as an intervention for reducing depression in older adults. However, little research has investigated the potential of BA to increase active engagement and well-being in older adults. The current pilot study sought to investigate the usefulness and acceptability of BA to promote well-being in a group of non-clinical older adults. Participants (N = 18) aged between 65 and 86 (M = 77.82, SD = 5.59) who were retired and living independently in the community were provided a 6-week BA program predominantly delivered online. Treatment retention, self-ratings, and participants' compliance to treatment principles indicate preliminary feasibility for the use of BA as an approach for increasing active engagement in older adult populations. Participants also provided feedback on their experiences with the program post-intervention via individual structured interviews. Thematic analysis of these data revealed that participants found the program to be beneficial in terms of increased self-awareness and social engagement, and provided several recommendations for improving acceptability of the program and workbook. The unexpected events relating to the first wave of the novel coronavirus (COVID-19) led to necessary adaptations to delivery modalities, and provided the researchers with an opportunity to investigate the use of a structured well-being program on a high-risk population during a pandemic. Our findings support the proposition that BA is a suitable intervention for increasing engagement and well-being in older adults, provide insight into adapting programs for older adults, and suggest next steps for testing intervention efficacy.

‘Destroyed Lung’: A Marker of Sequel of ‘Far Advanced’ Radiological Type of Pulmonary Tuberculosis’

Pulmonary Tuberculosis is caused by bacilli mycobacterium tuberculosis and known to infect human race since the dawn of history and archaeological evidence has traced its association in neolithic times. Tuberculosis is the most common infectious lung disease in India with significant mortality and morbidity. Tuberculosis can cause diverse thoracic presentations ranging from nodules, consolidations&amp; cavitation, mediastinal adenopathy, pleural effusion to diffuse endobronchial disease presenting like bronchial asthma. Due to diverse presentations, diagnosis is many times delayed due to lack of suspicion by treating general physicians and rational treatment not offered in time. In spite of awareness by government organizations and considered as a ‘global health issue of concern’ by the World Health organization, tuberculosis is still considered as a social stigma. Destroyed lung is described in literature and known as a complication of pulmonary tuberculosis. Destroyed lung is defined as combination of pleural and parenchymal lung destruction with cavitation, bronchiectasis, loss of lung volume and mediastinal herniation to diseased side. In this case series, we have reported two cases with history of pulmonary tuberculosis in the past and received adequate anti-tuberculosis treatment. Both were having residual chronic lung disease and symptoms causing significant impact on quality of life with recurrent hospitalization, hospital visits and cost of care. One patient has a history of delayed diagnosis and ATT was started after maximum lung destruction due to a tuberculous process that has already occurred. In this patient tuberculosis was cured but residual lung damage or sequel presenting as destroyed lung. In the second case, tuberculosis was diagnosed in adequate time but the patient has defaulted due to adverse events of ATT and he has taken medications as per his own tolerance. Neither adherence nor compliance was acceptable in the second case and resulted in a partially treated case of pulmonary tuberculosis. Ongoing lung destruction in the second case would be the cause for destroyed lungs in absence of irrational medicines in today’s era of good quality ATT. Destroyed lung is preventable with early diagnosis, prompt evaluation with microscopy and nucleic acid amplification tests and treatment with universally available, acceptable and affordable free ATT as National guidelines. 'Destroyed lung' are having a significant impact on quality of life and health expenditure and are considered as ‘radiological stigma’ of Tuberculosis. Radiological classifications of tuberculosis are less used now, and, it can be justified in grading of disease severity and aggressive treatment planning. Radiological classifications also help in predicting complications such as ‘destroyed lung’ during evolution of advanced pulmonary tuberculosis disease which can be prevented with timely diagnosis and use of rational treatment with good clinical and radiological outcome.

SMAD4 depletion contributes to endocrine resistance by integrating ER and ERBB signaling in HR + HER2− breast cancer

Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2−) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2− breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2− breast cancer patients.

Incorporating Design Based Implementation Research with a Randomized Controlled Trial to develop and evaluate the efficacy of playful rational number learning

We combine design-based implementation research with a pre-registered RCT to address a long-standing challenge in psychological science: How to use psychological principles to address real-world problems while designing and implementing interventions in the field. We posit this as a design methodology for optimizing the translation between psychological science and real-world applications. We tested the efficacy of an extensively co-designed version of a game-based rational number intervention, Fraction Ball, versus “business-as-usual” math instruction and physical education in a sample of 4th/5th grade Latine students (N = 360). Insights from nine co-design sessions with 20 teachers informed revisions and additions to a previous version of Fraction Ball, strengthening impacts across 10 of 12 rational number subtests. This methodology provides insights for translating psychological science research and scaling it to address real-world educational needs, such as play-based interventions that improve rational number understanding in authentic contexts.