Stages Of Thedisease Research Articles

Epidemiological profile of neuroendocrine tumors in adults in Brazil.

Neuroendocrine tumors (NETs) are a set of diseases that originate from neuroendocrine cells, which comprises a diffuse endocrine system present in various organs of the body. These tumors are more frequent in the gastrointestinal tract (70%) and the bronchopulmonary system (20%-30%). A NET incidence rate of 1-5 per 100,000 inhabitants has been estimated for several European countries and the USA employing 20 years of data. However, no comprehensive studies on this rare neoplasm are available in Brazil. In this context, the aim of this study was to characterize the epidemiological NET profile in the country. This is a retrospective descriptive observational study based on data from Hospital Cancer Records available at the Brazilian National Cancer Institute and the São Paulo Oncocentro Foundation. Demographic, clinical and treatmentrelated variables were analyzed from selected cases employing descriptive statistics. A total of 15,859 cases were identified, most occurring in males (53.4%) and in individuals under 65 years old (63.3%). Small cell carcinoma was the most frequent histological type (46.7%). Bronchopulmonary tumors were the most frequent NETs, followed by pancreatic tumors, with cases mostly concentrated in high complexity centers in the Brazilian Southeast and treated mainly with surgery and chemotherapy, with over half of the patients diagnosed in advanced stages of the disease.

Refractive surgical approaches to keratoconus: A systematic review and network meta-analysis.

Advancements in diagnostic methods and surgical techniques for keratoconus (KC) have increased non-invasive treatment options. Successful surgical planning for KC involves a combination of clinical science, empirical evidence, and surgical expertise. Assessment of disease progression is crucial, and halting the progression should be the focus if it is progressive. While surgeons used to rely on experience alone to decide the surgical method, comparing the network of primary factors, such as visual acuity, across studies can help them choose the most appropriate treatments for each patient and achieve optimal outcomes. Meticulous tabulation methods facilitate interpretation, highlighting the importance of selecting the correct surgical and rehabilitation approach based on each patient's condition and stage of the disease. We detail the outcomes of a comprehensive network meta-analysis comparing the effectiveness of various combined therapeutic refractive treatments for KC at identical stages of the disease, spanning four distinct follow-up intervals. Additionally, the comprehensive analysis suggests that for corneas with optimal best corrected visual acuity (BCVA) preoperatively (classified as regular), combining phakic intraocular lenses with intracorneal ring segments (ICRS) and corneal cross-linking (CXL) could offer the best therapeutic approach provided the disease stage does not exceed stage 3. For irregular corneas, although initial follow-ups show a significant difference in BCVA with surface ablation, longer-term follow-ups recommend combining surface ablation with ICRS and CXL, especially at higher stages.

Alterations in spatiotemporal characteristics of dynamic networks in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is characterized by altered patterns of brain functional connectivity (FC). However, the nature and extent of alterations in the spatiotemporal characteristics of dynamic FC in JME patients remain elusive. Dynamic networks effectively encapsulate temporal variations in brain imaging data, offering insights into brain network abnormalities and contributing to our understanding of the seizure mechanisms and origins. Resting-state functional magnetic resonance imaging (rs-fMRI) data were procured from 37 JME patients and 37 healthy counterparts. Forty-seven network nodes were identified by group-independent component analysis (ICA) to construct the dynamic network. Ultimately, patients' and controls' spatiotemporal characteristics, encompassing temporal clustering and variability, were contrasted at the whole-brain, large-scale network, and regional levels. Our findings reveal a marked reduction in temporal clustering and an elevation in temporal variability in JME patients at the whole-brain echelon. Perturbations were notably pronounced in the default mode network (DMN) and visual network (VN) at the large-scale level. Nodes exhibiting anomalous were predominantly situated within the DMN and VN. Additionally, there was a significant correlation between the severity of JME symptoms and the temporal clustering of the VN. Our findings suggest that excessive temporal changes in brain FC may affect the temporal structure of dynamic brain networks, leading to disturbances in brain function in patients with JME. The DMN and VN play an important role in the dynamics of brain networks in patients, and their abnormal spatiotemporal properties may underlie abnormal brain function in patients with JME in the early stages of the disease.

The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Materials and Methods: Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Results: Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP , but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). Conclusion: The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

Consistent and informed choice of drug and route of administration is key to increasing adherence to osteoarthritis treatment

The need to follow an integrated approach when prescribing treatment for patients suffering from osteoarthritis (OA) is beyond doubt. It is clear that success depends on the implementation of recommendations for both lifestyle modification and the introduction of pharmacological agents with different compositions and mechanisms of action aimed at reducing pain, stiffness, inflammation, normalizing joint function, and preventing cartilage destruction. The arsenal of such drugs is increasing, and the evidence base of effectiveness and safety is being enriched. Considering the heterogeneity of OA patients seeking help in terms of gender, age, body mass index, financial wealth, comorbidity, clinical manifestations of the disease, radiological stage of the disease and its duration, experience of previous treatment, a reasonable and agreed upon choice with the patient not only of the drug is relevant, but also the method of administration. The article provides a clinical example of a justified and coordinated choice of treatment for a patient with a generalized form of OA, synovitis of the knee joint, suffering from obesity, depression, low adherence to treatment using the example of prescribing a chondroprotector, the active component of which is a bioactive extract from small sea fish. The treatment effect was confirmed by clinical and instrumental assessment methods over time.

Brainstem Chipmunk Sign: A Diagnostic Imaging Clue across All Subtypes of Alexander Disease.

While classic brain MR imaging features of Alexander disease have been well-documented, lesional patterns can overlap with other leukodystrophies, especially in the early stages of the disease or in milder phenotypes. We aimed to assess the utility of a new neuroimaging sign to help increase the diagnostic specificity of Alexander disease. A peculiar bilateral symmetric hyperintense signal on T2-weighted images affecting the medulla oblongata was identified in an index patient with type I Alexander disease. Subsequently, 5 observers performed a systematic MR imaging review for this pattern by examining 55 subjects with Alexander disease and 74 subjects with other leukodystrophies. Interobserver agreement was assessed by the κ index. Sensitivity, specificity, and receiver operating characteristic curves were determined. The identified pattern was present in 87% of subjects with Alexander disease and 14% of those without Alexander disease leukodystrophy (P < .001), 3 with vanishing white matter, 4 with adult polyglucosan body disease, and 3 others. It was found equally in both type I and type II Alexander disease (28/32, 88% versus 18/21, 86%; P = .851) and in subjects with unusual disease features (2/2). Sensitivity (87.3%; 95% CI, 76.0%-93.7%), specificity (86.5%; 95% CI, 76.9%-92.5%), and interobserver agreement (κ index = 0.82) were high. The identified pattern in the medulla oblongata, called the chipmunk sign due to its resemblance to the face of this rodent, is extremely common in subjects with Alexander disease and represents a diagnostic tool that can aid in early diagnosis, especially in subjects with otherwise atypical MR imaging findings and/or clinical features.

Abstract PO2-27-06: ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer

Abstract Metastasis to distant organs stands as the primary contributor to mortality in cases of breast cancer. While localized breast cancer boasts a 5-year survival rate of roughly 99%, this figure drastically declines to approximately 26% for patients afflicted with distant metastasis. Regrettably, the current therapeutic landscape lacks efficacious and targeted interventions for the treatment of metastatic breast cancer. Our investigation has revealed a significant upregulation of S100A4 in metastatic breast cancer tissues, with notably high expression observed in the malignant pleural effusion of patients in advanced stages of the disease. Upon acceptance of the effective treatment, the expression of S100A4 in malignant pleural effusion decreased, along with a decrease in several cytokines, including IL-6, IL-8, CCL2, and CCL5. The breast cancer cellular models demonstrated that ANXA9 has the ability to regulate the excretion of S100A4 from cells into the surrounding medium. Similarly, the mice model of pleural metastasis indicated that the downregulation of ANXA9 (sh-ANXA9) resulted in decreased levels of S100A4 and cytokines IL-6, IL-8, CCL2, and CCL5 in the mice's hydrothorax. Additionally, our findings suggest that ANXA9 regulates the excretion of S100A4 through phosphorylation of ANXA9. The cellular membrane harbored phosphorylated ANXA9, which exhibited two phosphorylation sites. Upon mutation of these sites, the level of ANXA9 phosphorylation decreased, leading to a reduction in the exocrine release of ANXA9 from cells into the medium. Our research further revealed the significant involvement of ANXA9 in facilitating the progression of breast cancer, thereby suggesting that therapeutic interventions targeting ANXA9 could prove efficacious in treating metastatic breast cancer. This work was supported by Shanghai Sailing Program to Dengfeng Li (No. 20YF1437800), grant from the National Natural Science Foundation of China to Dengfeng li (No. 82103454) and grant from the National Natural Science Foundation of China to Lin Fang (No. 82073204). Citation Format: Xiqian Zhou, Dengfeng Li, Lin Fang, Junyong Zhao. ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-06.

Circulating immune profile in granulomatosis with polyangiitis reveals distinct patterns related to disease activity

Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by recurrent relapses that can cause severe tissue damage and life-threatening organ dysfunction. Multiple immune cells and cytokines/chemokines are involved in the different stages of the disease. Immune profiling of patients may be useful for tracking disease activity, however, reliable immune signatures for GPA activity are lacking. In this study, we examined circulating immune profiles in GPA patients during active and remission disease states to identify potential immune patterns associated with disease activity.The distribution and phenotypic characteristics of major circulating immune cells, and the profiles of circulating cytokines/chemokines, were studied on cryopreserved peripheral blood mononuclear cells from GPA patients (active, n = 20; remission, n = 20) and healthy controls (n = 20) leveraging a 40-color optimized multicolor immunofluorescence panel (OMIP-69) and in serum using a 46-plex Luminex multiplex assay, respectively.Deep phenotyping uncovered a distinct composition of major circulating immune cells in active GPA and GPA in remission, with the most significant findings emerging within the monocyte compartment. Our detailed analysis revealed circulating monocyte diversity beyond the conventional monocyte subsets. We identified eight classical monocyte populations, two intermediate monocyte populations, and one non-classical monocyte population. Notably, active GPA had a higher frequency of CD45RA+CCR5+CCR6−CCR7+/lowCD127−HLA-DR+CD2− classical monocytes and a lower frequency of CD45RA−CCR5-/lowCCR6−CCR7−CD127−HLA-DR+CD2+/− classical monocytes, which both strongly correlated with disease activity. Furthermore, serum levels of CXCL1, CXCL2, and CCL20, all linked to monocyte biology, were elevated in active GPA and correlated strongly with disease activity.These findings shed light on the circulating immune profile of GPA and may lead to immune signature profiles for assessing disease activity. Monocytes in particular may be studied further as potential markers for monitoring GPA.

Current Evidence in the Management of Central Skull Base Osteomyelitis: A Systematic Review

Objectives Based on current evidence, this systematic review focuses on various gray areas related to these patients' diagnosis, management, and follow-up in central skull base osteomyelitis (CSBO). Study Design A systematic review of all case reports and observational studies. Methods We systematically searched PubMed, Scopus database, Cochrane database, U.K. clinicaltrails.gov registry, and World Health Organization International Clinical Trials Registry Platform and included all reports as per our inclusion criteria. Data was analyzed systematically, and we made essential observations. Results Out of 179 articles, 25 were selected according to inclusion criteria and quality assessment. Among the 44 patients, refractory headache (95%) was the most common presentation, followed by cranial nerve paralysis (82%) and Pseudomonas (32%) as the most common bacteria. Contrary to the available literature the disease cure was worse in those who underwent targeted biopsy (64% vs. 36%, p = 0.023) and surgical debridement (61% vs. 39%, p = 0.013) in the late stages of the disease. Conclusion Otogenic osteomyelitis can spread to central skull bones in the absence of obvious ear symptoms. Early diagnosis and intervention of CSBO before progression to late stages can help decrease significant morbidity and mortality.

Neuroimaging Changes and Treatment Outcome of Tubercular Meningitis- Experiences 22 Cases in a Tertiary Care Center

Background: Tuberculous meningitis (TBM) is caused by Mycobacterium tuberculosis (M. tuberculosis) and is the most common form of central nervous system (CNS) tuberculosis (TB).The prevalence of TB meningitis remains largely underestimated because clinical manifestations are nonspecific in early stages of the disease. Prompt diagnosis is critical for initiating appropriate therapy, facilitating measures to prevent dissemination of this highly contagious disease and to combat fatal complication in children Aims: To evaluate the role of neuroimaging changes and treatment outcome of tubercular meningitis. Methods: This prospective hospital-based cohort study was conducted in Department of Paediatric Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during January 2022 to December 2022. Children age belonged to 1 month to 10 year diagnosed as TBM during study period were enrolled in this study. Detailed history, clinical examination, CSF analysis and other relevant investigations were done. Data were recorded in standard questionnaire. Statistical analyses of the results were obtained by using window-based computer software devised with Statistical Packages for Social Sciences (SPSS-22). Results: Total 22 diagnosed case of TBM was enrolled and evaluated. Among them two third (63.63%) children were in 5-10 year age group. Male (59%) were outnumbered than female (36.36 %).Male female ratio was 1.6:1. More than half (59%) of patients came from urban area. All of the patients were vaccinated. Cent percent (100%) patients were presented with fever followed by headache (77.27%), sign of meningeal irritation (54.54%), vomiting (54.54%) and seizures (50%). Most common complication was hemiparesis (45.45%) followed by cranial nerve palsy (40.90%), visual problem (9.09%) and hydrocephalus (4.54%). Abnormal neuroimaging changes were found in 100% cases. Common findings were hydrocephalus (40.90%), tubercloma (36.36%), basilar enhancement (18.18%), Benign enlargement of subdural space &amp; cerebellar hyperintensity (9%) and thalamic infract was present in 4.54% cases. Anti TB and steroid treatment were given in 100% cases and among them18.18% cases were required shunt procedure. More than one-third cases (40.90%) were completely normal without any no sequelae. Among abnormal sequelae found in two third (59%) cases. Speech impairment (36.36%) was most common followed by GDD (18.18%), hemiparesis (13.63%), quadriparesis (9.09%) and epilepsy in 9.09% cases. Conclusion: In our study all children of TBM were presented with fever followed by other predominant clinical features headache, vomiting, seizures and   sign of meningeal irritation.  Abnormal neuroimaging changes were found in all cases. Common findings were  basilar enhancement, hydrocephalus, tubercloma, benign enlargement of subdural space &amp; cerebellar hyper intensity and thalamic infract. After treatment more than one-third cases were completely normal without any no sequelae. J Bangladesh Coll Phys Surg 2024; 42: 214-218

The Importance of In Vivo Reflectance Confocal Microscopy in a Case of Desmoplastic Melanoma

Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma.

Cutaneous Mucormycosis in Buffalos in the Brazilian Amazon Biome

This is the first description of cutaneous mucormycosis in buffalo in the Brazilian Amazon biome. All buffalo showed apathy, inappetence, weight loss, reluctance to move, and prolonged sternal decubitus. Of the four affected animals, two died 15 and 30 days after the appearance of clinical signs. In the initial phase, the skin lesions were rounded areas with dry central regions, sensitive to palpation, with protruding edges and diameters ranging from 8 cm to 15 cm. These areas of necrosis were isolated or coalescing and present mainly on the limbs and sides. In an advanced stage of the disease, there was detachment of the skin from the necrotic areas with extensive wound formation, which sometimes exposed the subcutaneous tissue. The histopathology of the skin showed a multifocal inflammatory infiltrate composed of intact and degenerated eosinophils surrounded by epithelioid macrophages. At the center of these areas was a focally extensive area of epidermal ulceration characterized by intact and degenerated neutrophils, the necrosis of epithelial cells, and the accumulation of fibrin and erythrocytes. The mycological culture was positive for Rhizopus sp. The diagnosis of cutaneous dermatitis caused by Rhizopus sp. was based on clinical signs, macroscopic and histopathological findings, and the identification of the fungus by mycological and molecular techniques.

Automatic Spontaneous Speech Analysis for the Detection of Cognitive Functional Decline in Older Adults: Multilanguage Cross-Sectional Study.

The rise in life expectancy is associated with an increase in long-term and gradual cognitive decline. Treatment effectiveness is enhanced at the early stage of the disease. Therefore, there is a need to find low-cost and ecological solutions for mass screening of community-dwelling older adults. This work aims to exploit automatic analysis of free speech to identify signs of cognitive function decline. A sample of 266 participants older than 65 years were recruited in Italy and Spain and were divided into 3 groups according to their Mini-Mental Status Examination (MMSE) scores. People were asked to tell a story and describe a picture, and voice recordings were used to extract high-level features on different time scales automatically. Based on these features, machine learning algorithms were trained to solve binary and multiclass classification problems by using both mono- and cross-lingual approaches. The algorithms were enriched using Shapley Additive Explanations for model explainability. In the Italian data set, healthy participants (MMSE score≥27) were automatically discriminated from participants with mildly impaired cognitive function (20≤MMSE score≤26) and from those with moderate to severe impairment of cognitive function (11≤MMSE score≤19) with accuracy of 80% and 86%, respectively. Slightly lower performance was achieved in the Spanish and multilanguage data sets. This work proposes a transparent and unobtrusive assessment method, which might be included in a mobile app for large-scale monitoring of cognitive functionality in older adults. Voice is confirmed to be an important biomarker of cognitive decline due to its noninvasive and easily accessible nature.

Early intervention and care for Diabetic Foot Ulcers in Low and Middle Income Countries: Addressing challenges and exploring future strategies: A narrative review.

Diabetic Foot Ulcers (DFUs) are a significant health concern, particularly in Low- and Middle-Income Countries (LMICs). This review explores key strategies for managing DFUs in LMICs, including integrating podiatry, endocrinology, and wound care services, educating patients, promoting self-care, and preventive measures to reduce amputation rates. A comprehensive literature review was conducted, focusing on studies conducted in Low and Middle Income Countries to facilitate a qualitative analysis. The review examined the aetiology and risk factors to developing DFUs, clinical presentation, multidisciplinary management and evidence based interventions, challenges to the provision of care and future directions, all pertaining to DFUs in low and middle income countries. The aetiology and risk factors contributing to the development of DFUs are complex and multifaceted. Factors such as limited access to health care, inadequate diabetes management, and socioeconomic disparities significantly influence the incidence of DFUs. Clinical presentation varies, with patients often presenting at advanced stages of the disease due to delayed or missed diagnoses. Multidisciplinary management, incorporating podiatry, endocrinology, and wound care services, has exhibited substantial promise in enhancing patient outcomes. Evidence-based interventions, including offloading techniques, wound debridement, and the use of advanced wound dressings, have proven effective in promoting ulcer healing. The burden of DFUs in LMICs requires comprehensive strategies. Integrating podiatry, endocrinology, and wound care services, along with patient education and self-care practices, is essential for reducing amputations and improving patients' quality of life. Regular follow-up and early detection are vital for effective DFU management, emphasizing the need for ongoing research and investment in LMIC health care infrastructure. Embracing these multidisciplinary, patient-centered approaches can effectively address the challenge of DFUs in LMICs, leading to better patient outcomes and improved quality of life.

The Fetal Alcohol Spectrum Disorders—An Overview of Experimental Models, Therapeutic Strategies, and Future Research Directions

Since the establishment of a clear link between maternal alcohol consumption during pregnancy and certain birth defects, the research into the treatment of FASD has become increasingly sophisticated. The field has begun to explore the possibility of intervening at different levels, and animal studies have provided valuable insights into the pathophysiology of the disease, forming the basis for implementing potential therapies with increasingly precise mechanisms. The recent reports suggest that compounds that reduce the severity of neurodevelopmental deficits, including glial cell function and myelination, and/or target oxidative stress and inflammation may be effective in treating FASD. Our goal in writing this article was to analyze and synthesize current experimental therapeutic interventions for FASD, elucidating their potential mechanisms of action, translational relevance, and implications for clinical application. This review exclusively focuses on animal models and the interventions used in these models to outline the current direction of research. We conclude that given the complexity of the underlying mechanisms, a multifactorial approach combining nutritional supplementation, pharmacotherapy, and behavioral techniques tailored to the stage and severity of the disease may be a promising avenue for further research in humans.

Adaptation Process in Husbands of Iranian Women Undergoing Mastectomy From Diagnosis to Terminal Stages of the Disease: A Grounded Theory Study.

Breast cancer is the most common cancer in women and the second cause of cancer-related death. This research was performed to interpret the adaptation process among husbands of Iranian women undergoing mastectomy. In this grounded theory study, 23 participants were chosen purposefully and via convenient sampling. After interview with them about adaptation and ways of achieving it, note taking was done, which was analyzed via Strauss and Corbin approach. Six themes were extracted: Confrontation with crisis, Challenges and opportunities, husband transformation, supportive systems, attempts for life management, accepting an uninvited guest, with each having subclasses. According to the results of the present study the healthcare team and psychologists should identify this issue properly so that they could apply measures for facilitating the coping and acceptance of the issue in husbands of these patients.

Clinical case of management of a patient with Duchenne muscular dystrophy caused by deletion of exons 50–52 of the DMD gene against the background of pathogenetic therapy with viltolarsen

Duchenne muscular dystrophy (DMD) is the most common lumbar-limb muscular dystrophy with an X-linked recessive type of inheritance. It is characterized by a debut at an early age, rapidly progressive atrophy of the striated musculature of the limbs, trunk, heart muscle, which leads to loss of motor skills, severe cardiovascular and respiratory complications.&#x0D; Currently, a number of new drugs have appeared for the pathogenic therapy of MDD, the effectiveness of which is the most during its early initiation in the ambulatory stage of the disease. One of the new methods of MDD treatment is antisense oligonucleotide therapy. The application of this type of therapy is possible for certain mutations in the DMD gene and is recommended immediately after diagnosis. At the moment, the duration of this method of treatment in the Russian Federation is only a few years.&#x0D; In our article we discuss a clinical case of the study of a patient suffering from Duchenne muscular dystrophy caused by the deletion of 50–52 exons in the DMD gene, who is on therapy with steroids and Viltolarsen.&#x0D; A special feature of the case is the late application of Viltolarsen from the age of 9 years. The results of the observation demonstrate a significant effect in stabilization of motor skills, of the functioning of the cardiovascular and respiratory systems, which gives a chance to slow down the course of the disease, improve the quality of life and increase its duration, even taking into account the late initiation of pathogenic therapy.

Non-squamous Cancers of the Larynx.

Although non-squamous tumors of the larynx are really rare, they may not always be viewed from the same perspective in the multidisciplinary treatment approach once the diagnosis is made. In this review, non-squamous tumors of the larynx and current approaches in treatment will be discussed. When the studies and meta-analyses presented in the last 5years are evaluated, it is seen that these tumors usually show non-specific symptoms. Due to their submucosal location, the stage of the disease at the time of diagnosis is often advanced. In the literature, treatment may vary in these particular cases. The majority of non-squamous tumors of the larynx includes minor salivary gland tumors, neuroendocrine carcinomas, sarcomas, cartilage tumors, and malignant melanomas. Once treating a patient with these diagnoses, it should be kept in mind that the histopathological subtype is almost as important as the stage of the tumor.

Trends in the surgical treatment of glaucoma in recent decades

The analysis of trends in the surgical treatment of primary open-angle glaucoma (POAG) allows assessing changes in the indications for surgical treatment, the number of glaucoma surgery and their modifications, as well as the demographic characteristics of patients, duration of preoperative therapy and the effectiveness of treatment.The results indicate that over the past 20 years in the Russian Federation there was a shift towards an increasingly long-term therapeutic strategy used before the surgical stage of treatment, and, in general, a decrease in the number of performed glaucoma surgeries. There is much concern about late surgical treatment, which is confirmed by the established increase in the age of first-time operated patients, and the tendency to increase the number of operations at a far advanced stage of the disease. Most of the published studies on the postoperative hypotensive efficacy of surgery are of limited duration, which does not allow an adequate assessment of the results of treatment. Early appointment of medical hypotensive therapy after surgical intervention indicates a low interaction between outpatient and inpatient specialists, which hinders the possibility of early correction of postoperative problems. The recent increase in the number of scientific works, especially patents, focusing on the search for new technologies that can be implemented in glaucoma surgery, the development of modern drainage devices and the methods for prolonging the hypotensive effect after surgery gives a reason for optimism. The performed analysis dictates the need to develop and implement measures aimed at clearly defined indications for timely surgical treatment and creation of conditions for a complex relationship between the patient, outpatient ophthalmologist and glaucoma surgeon.

Beneficial versus Detrimental Effects of Complement–Microglial Interactions in Alzheimer’s Disease

Research indicates that brain-region-specific synapse loss and dysfunction are early hallmarks and stronger neurobiological correlates of cognitive decline in Alzheimer’s disease (AD) than amyloid plaque and neurofibrillary tangle counts or neuronal loss. Even though the precise mechanisms underlying increased synaptic pruning in AD are still unknown, it has been confirmed that dysregulation of the balance between complement activation and inhibition is a crucial driver of its pathology. The complement includes three distinct activation mechanisms, with the activation products C3a and C5a, potent inflammatory effectors, and a membrane attack complex (MAC) leading to cell lysis. Besides pro-inflammatory cytokines, the dysregulated complement proteins released by activated microglia bind to amyloid β at the synaptic regions and cause the microglia to engulf the synapses. Additionally, research indicating that microglia-removed synapses are not always degenerating and that suppression of synaptic engulfment can repair cognitive deficits points to an essential opportunity for intervention that can prevent the loss of intact synapses. In this study, we focus on the latest research on the role and mechanisms of complement-mediated microglial synaptic pruning at different stages of AD to find the right targets that could interfere with complement dysregulation and be relevant for therapeutic intervention at the early stages of the disease.