Group Of Diseases Research Articles

Colombian ocular diseases epidemiology study (CODES): glaucoma incidence and sociodemographic characterisation 2015–2020

ABSTRACT Clinical relevance Glaucoma encompasses a group of eye diseases that progressively damage the optic nerve, leading to vision loss and blindness. Understanding the incidence and demographic distribution is vital for public health planning and patient care. Background Previous small-scale studies in Colombia have reported the prevalence of glaucoma in individuals over 40 years between 1.1% and 5.29%. These data may not fully capture the true extent of the disease. Furthermore, with the ageing population, the incidence of glaucoma is likely to increase, highlighting the need for up-to-date incidence data to guide healthcare planning. Methods Data were obtained from the Social Protection Information System, the primary health record repository of Colombia, using the International Classification of Disease 10 for glaucoma. Crude incidence rates were calculated and adjusted for sex, age, and gender. The 2020 incidence was compared with estimated rates from previous years to assess the impact of the coronavirus disease 2019 lockdown. A standardised morbidity map was created to show regional variations. Results The average incidence of glaucoma in Colombia was 17.36 per 1,000 inhabitants, increasing from 12.29 in 2015 to 24.22 in 2019. Of the 212,700 reported cases, 60.75% were females. Primary open-angle glaucoma was the most prevalent type, with significant incidence in the elderly over 70 years of age, irrespective of sex. Bogotá, Antioquia, and Valle del Cauca had the highest numbers of new cases. Conclusion The increasing incidence of glaucoma and its demographic and geographical variations necessitate the awareness of ophthalmologists and optometrists. This study emphasises the need for continuous monitoring, effective interventions, and developing healthcare strategies to address the escalating challenge of glaucoma in Colombia.

The Clinical Approach to Interstitial Lung Disease in Childhood: A Narrative Review Article

Interstitial lung disease (ILD) comprises a group of respiratory diseases affecting the interstitium of the lungs, which occur when a lung injury triggers an abnormal healing response, and an inflammatory process leads to altered diffusion and restrictive respiratory dysfunction. The term “interstitial” may be misleading, as other components of the lungs are usually also involved (epithelium, airways, endothelium, and so on). Pediatric conditions (childhood interstitial lung disease, chILD) are different from adult forms, as growing and developing lungs are affected and more diverse and less prevalent diseases are seen in childhood. Diffuse parenchymal lung disease (DPLD) and diffuse lung disease (DLD) can be used interchangeably with ILD. Known etiologies of chILD include chronic infections, bronchopulmonary dysplasia, aspiration, genetic mutations leading to surfactant dysfunction, and hypersensitivity pneumonitis due to drugs or environmental exposures. Many forms are seen in disorders with pulmonary involvement (connective tissue disorders, storage diseases, malignancies, and so on), but several conditions have unknown origins (desquamative pneumonitis, pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia in infancy, and so on). Currently, there is no consensus on pediatric classification; however, age grouping is proposed as some specific forms are more prevalent in infancy (developmental and growth abnormalities, surfactant dysfunction mutations, etc.) and others are usually seen in older cohorts (disorders in normal or immunocompromised hosts, systemic diseases, etc.). Clinical manifestations vary from mild nonspecific symptoms (recurrent respiratory infections, exercise intolerance, failure to thrive, dry cough, etc.) to a severe clinical picture (respiratory distress) and presentation related to the child’s age. The diagnostic approach relies on imaging techniques (CT), but further investigations including genetic tests, BAL, and lung biopsy (VATS) are needed in uncertain cases. Pharmacological treatment is mostly empiric and based on anti-inflammatory and immunomodulatory drugs. Lung transplantation for selected cases in a pediatric transplantation center could be an option; however, limited data and evidence are available regarding long-term survival. International collaboration is warranted to understand chILD entities better and improve the outcomes of these patients.

Revealing the clinical impact of MTOR and ARID2 gene mutations on MALT lymphoma of the alimentary canal using targeted sequencing

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are a group of diseases with marked heterogeneity, including clinical, immunohistochemical, and molecular heterogeneity. The disease remains unspecified in the genetic landscape with only a few sequencing studies to date; however, systematic studies of alimentary canal MALT lymphoma have not been reported. To better understand the genetics of this tumor, targeted sequencing in a group of 31 cases (including 2 esophageal, 2 colonic, 4 small intestinal, and 23 gastric cases) and two cases of lymph node hyperplasiawere performed. We found epigenetic regulation (DNMT3A, KMT2D, KMT2A, EP300, TET2, etc.), signaling pathways (APC, CHD8, TNFAIP3, TNFRSF14, ZAP70, NF1,), and tumor suppressor genes (TP53, BCORL1, FOXO1, ATM, etc.) involved. Moreover, we found MTOR gene mutations in 16% of the cases that made these patients more prone to recurrence and metastasis than those with MTOR wild type genes. More interestingly, ARID2 mutations were detected in 32% of all the cases, and the mutation rate was higher and statistically significant in Helicobacter pylori (Hp)-negative patients in the gastric group. Therefore, this study found that MTOR and ARID2 gene mutations have pathogenic and prognostic implications.

The historical background of hereditary cystatin C amyloid angiopathy: Genealogical, pathological, and clinical manifestations.

Hereditary cystatin C amyloid angiopathy (HCCAA) is an Icelandic disease that belongs to a disease class called cerebral amyloid angiopathy, a group of heterogenous diseases presenting with aggregation of amyloid complexes and deposition predominantly in the central nervous system. HCCAA is dominantly inherited, caused by L68Q mutation in the cystatin C gene, leading to aggregation of the cystatin C protein. HCCAA is a very progressive and severe disease, with widespread cerebral and parenchymal cystatin C and collagen IV deposition within the central nervous system (CNS) but also in other organs in the body, for example, in the skin. Most L68Q carriers have clinical symptoms characterized by recurrent hemorrhages and dementia, between the age of 20-30 years. If the carriers survive the first hemorrhage, the frequency and severity of the hemorrhages tend to increase, resulting in death at average of 30 years with mean number of major hemorrhages ranging from 3.2 to 3.9 over a 5-year average life span. The pathogenesis of the disease in carriers is very similar in the CNS and in the skin based on autopsy studies, thus skin biopsies can be used to monitor the progression of the disease by quantifying the cystatin C immunoreactivity. The cystatin C deposition always colocalizes with collagen IV and fibroblasts in the skin are found to be the main cell type responsible for the deposition of both proteins. No therapy is available for this devastating disease.

Mortality in patients receiving renal replacement therapy in South Korea.

This study analyzed data from the end-stage renal disease patient registry collected by the Korean Society of Nephrology to explore trends in mortality among dialysis patients from 2001 to 2022. Mortality was analyzed in two ways: firstly, using the annual mortality rate; and secondly, by assessing survivability after a certain period of time since the initiation of dialysis. Additionally, we categorized the causes of death by disease group annually to observe how the proportions changed. Since 2001, annual mortality for dialysis patients generally declined, except for a rise in 2020 and 2021 among hemodialysis patients. Overall mortality rates for all dialysis patients dropped from 74.2/1,000 person-years in 2001 to 42.3/1,000 person-years in 2022, with a more pronounced decrease in peritoneal dialysis. While survival probability over the 5 years following initiation of dialysis has shown a steady increase, short-term mortality from 2018 to 2020 affected by coronavirus disease 2019 (COVID-19) has shown a yearly increase by age group, with a greater effect in those aged 75 years and older. The leading causes of death for all dialysis patients have changed little, in the order of heart disease, infection, and vascular problems. While annual mortality and survival probability after dialysis initiation have generally improved in dialysis patients, there has been a temporary deterioration during the COVID-19 pandemic, most pronounced in the elderly.

Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity

This study retrospectively investigated the impact of interleukin-1 receptor-associated kinase-3 (IRAK-3/IRAK-M) silencing by methylation on the likelihood of multiple sclerosis (MS) activity. This cross-sectional study included 90 patients with MS: 45 with active disease (Group 1), 45 in remission (Group 2), and 45 healthy controls. The study included quantitation of IRAK-3 methylation index (MI%), IRAK-3 mRNA, and myeloid differentiation factor88 (MyD88) and assessment of NF-κB activity.IRAK-3 MI% was significantly higher in group 1 compared to group 2, accompanied by lower IRAK-3 mRNA expression, elevated circulating MyD88, and increased NF-κB activity. IRAK-3 MI% correlated negatively with its transcript and positively with MyD88 and NF-κB activity. A logistic regression model was created to predict active demyelination. The C-index was 0.924, which indicates a very strong prediction model. Within the limitations of current work, IRAK-3 methylation level seems to be a promising candidate biomarker for identifying MS patients at risk of relapse.

Transcriptomic analyses of differentially expressed human genes, micro RNAs and long-non-coding RNAs in severe, symptomatic and asymptomatic malaria infection

Malaria transmission and endemicity in Africa remains hugely disproportionate compared to the rest of the world. The complex life cycle of P. falciparum (Pf) between the vertebrate human host and the anopheline vector results in differential expression of genes within and between hosts. An in-depth understanding of Pf interaction with various human genes through regulatory elements will pave way for identification of newer tools in the arsenal for malaria control. Therefore, the regulatory elements (REs) involved in the over- or under-expression of various host immune genes hold the key to elucidating alternative control measures that can be applied for disease surveillance, prompt diagnosis and treatment. We carried out an RNAseq analysis to identify differentially expressed genes and network elucidation of non-coding RNAs and target genes associated with immune response in individuals with different clinical outcomes. Raw RNAseq datasets, retrieved for analyses include individuals with severe (Gambia—20), symptomatic (Burkina Faso—15), asymptomatic (Mali—16) malaria as well as uninfected controls (Tanzania—20; Mali—36). Of the total 107 datasets retrieved, we identified 5534 differentially expressed genes (DEGs) among disease and control groups. A peculiar pattern of DEGs was observed, with individuals presenting with severe/symptomatic malaria having the highest and most diverse upregulated genes, while a reverse phenomenon was recorded among asymptomatic and uninfected individuals. In addition, we identified 141 differentially expressed micro RNA (miRNA), of which 78 and 63 were upregulated and downregulated respectively. Interactome analysis revealed a moderate interaction between DEGs and miRNAs. Of all identified miRNA, five were unique (hsa-mir-32, hsa-mir-25, hsa-mir-221, hsa-mir-29 and hsa-mir-148) because of their connectivity to several genes, including hsa-mir-221 connected to 16 genes. Six-hundred and eight differentially expressed long non coding RNA (lncRNA) were also identified, including SLC7A11, LINC01524 among the upregulated ones. Our study provides important insight into host immune genes undergoing differential expression under different malaria conditions. It also identified unique miRNAs and lncRNAs that modify and/or regulate the expression of various immune genes. These regulatory elements we surmise, have the potential to serve a diagnostic purpose in discriminating between individuals with severe/symptomatic malaria and those with asymptomatic infection or uninfected, following further clinical validation from field isolates.

CXCL12/CXCR4 as a potential axis in diagnosis and predicting disease severity in COVID-19 patients: a new perspective

Abstract Objectives Coronavirus disease 2019 (COVID-19) exhibits variations in terms of patients’ clinical symptoms and levels of routinely employed biochemical markers. The aim of the current study was to determine the correlation between serum levels of the C-X-C chemokine ligand type 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4), one of its specific receptors, and disease severity in COVID-19 patients. Methods Sixty-nine patients were diagnosed with COVID-19 from February to July 2021, and a healthy control group of 39 individuals were enrolled in the study. Patients were divided into subgroups: mild-moderate and severe. Serum CXCL12 and CXCR4 levels were measured using the enzyme-linked immunosorbent assay method. Results CXCL12 and CXCR4 concentrations were both significantly higher in the clinically severe disease group compared to the mild-moderate disease group (p<0.05 in both groups). CXCL12 and CXCR4 levels were also significantly higher in the patients with clinically mild-moderate disease compared to the control group (p<0.001 and p<0.05, respectively). Both CXCL12 and CXCR4 levels were correlated with clinical severity. Serum CXCL12 and CXCR4 levels were significantly positively correlated. Assuming a cut-off value of 1.44 ng/mL, serum CXCL12 levels showed 98 % sensitivity and 84 % specificity to distinguish between COVID-19 patients and healthy individuals (AUC=0.98, p<0.001, 95 % CI=0.95–1.0). Serum CXCR4 levels distinguished individuals with COVID-19 from healthy controls with 88 % sensitivity and 72 % specificity at a cut-off value of 69.7 pg/mL (AUC=0.82, p<0.001, 95 % CI=0.74–0.9). Conclusions Serum CXCL12 and CXCR4 levels may be included among the biomarkers used to differentiate patients with COVID-19 and determine the clinical severity of the disease.

Advances in Ubiquitination and Proteostasis in Retinal Degeneration.

Retinal degeneration (RD) is a group of chronic blinding diseases characterised by progressive retinal cell death. As the disease progresses, vision deteriorates due to retinal cell death and impaired retinal integrity, eventually leading to complete loss of vision. Therefore, the function and environmental homeostasis of the retina have an important impact on the pathogenesis and treatment of RD. Ubiquitination, as a complex post-translational modification process, plays an essential role in maintaining retinal homeostasis and normal function. It covalently combines ubiquitin with protein through a series of enzyme-mediated reactions, and participates in cell processes such as gene transcription, cell cycle process, DNA repair, apoptosis and immune response. At the same time, it plays a central role in protein degradation. There are two major protein degradation systems in eukaryotic cells: the ubiquitin-proteasome system and the autophagy-lysosomal system. The protein degradation pathway maintains retinal protein homeostasis by reducing abnormal protein accumulation in the retina through two modes of degradation. Either dysregulation of ubiquitination or disruption of protein homeostasis may lead to the development of RD. This article aims to comprehensively review recent research progress on ubiquitin-related genes, proteins and protein homeostasis in the pathogenesis of RD, and to summarize the potential targeted therapy strategies for it. The review is expected to provide valuable guidance for further development and application of ubiquitination in RD.

Genetic prion disease – fatal familial insomnia (clinical case)

Background. Fatal familial insomnia is a rare genetically determined neurodegenerative disorder from the group of prion diseases. Its main cause is the autosomal dominant D178N mutation of the PRNP gene, which leads to the synthesis of the pathological prion protein PrP.The aim. Using the example of a clinical case to describe an example of the early onset of fatal familial insomnia in a teenager, a clinical example of its management.Materials and methods. Female patient V., 16 years old, of hyposthenic constitution, undernourished, with negative family history (multiple sclerosis in her paternal grandmother) for the first time consulted a neurologist in Tver for the complaints of superficial sleep, shortened to 4–5 hours, unspecific pain all over the body, periodic numbness in the upper limbs. Six months later, retardation of speech and movements, changes in gait, and intentional tremor occurred; sleep was shortened to 2 hours. In the future, the teenager lost the ability to independently maintain the vertical body position, the ability to walk without assistance, speech was reduced to syllable answers to questions. In order to verify the diagnosis and to carry out differential diagnosis with other neurodegenerative diseases, the girl underwent auxiliary research methods: detection of antibodies to nuclear antigens, magnetic resonance imaging, computer electroencephalography, polyexomal genome sequencing.Results. Based on the anamnesis, complaints, clinical picture and results of genetic research the final diagnosis of fatal familial insomnia was made. Due to the lack of etiological and pathogenetic therapy, the patient was subsequently provided with palliative medical care. The fatal outcome occurred 19 months after the onset of the disease.Conclusions. The presented clinical case reflects the complexity of managing patients with rare genetic diseases, confirms the need for mandatory polyexomal genome sequencing in order to verify the diagnosis, which allows timely palliative care

Humoral immune responses primed by the alteration of gut microbiota were associated with galactose-deficient IgA1 production in IgA nephropathy.

Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified. The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN. Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.

Plasma-based near-infrared spectroscopy for early diagnosis of lung cancer

Lung cancer (LC) continues to be a leading death cause in China, primarily due to late diagnosis. This study aimed to evaluate the effectiveness of using plasma-based near-infrared spectroscopy (NIRS) for LC early diagnosis. A total of 171 plasma samples were collected, including 73 healthy controls (HC), 73 LC, and 25 benign lung tumors (B). NIRS was utilized to measure the spectra of samples. Pre-processing methods, including centering and scaling, standard normal variate, multiplicative scatter correction, Savitzky-Golay smoothing, Savitzky-Golay first derivative, and baseline correction were applied. Subsequently, 4 machine learning (ML) algorithms, including partial least squares (PLS), support vector machines (SVM), gradient boosting machine, and random forest, were utilized to develop diagnostic models using train set data. Then, the predictive performance of each model was evaluated using test set samples. The study was conducted in 5 comparisons as follows: LC and HC, LC and B, B and HC, the diseased group (D) and HC, as well as LC, B and HC. Among the 5 comparisons, SVM consistently generated the best performance with a certain pre-processing method, achieving overall accuracy of 1.0 (kappa: 1.0) in the comparisons of LC and HC, B and HC, as well as D and HC. Pre-processing was identified as a crucial step in developing ML models. Interestingly, PLS demonstrated remarkable stability and relatively high predictive performance across the 5 comparisons, even though it did not achieve the top results like SVM. However, none of these algorithms were able to effectively distinguish B from LC. These findings indicate that the combination of plasma-based NIRS with ML algorithms is a rapid, non-invasive, effective, and economical method for LC early diagnosis.

Evaluasi Rasionalitas Insulin Pada Pasien Diabetes Mellitus Tipe 2 Rawat Jalan di RSUD Kota Madiun Periode 2022

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia that occurs due to defects in insulin secretion, insulin action or both. Diabetes mellitus (DM) is currently a global health threat. Various epidemiological studies have shown an increase in the incidence and prevalence of DM in the world. Based on data from the profile of the East Java Health Office in 2021, it is estimated that DM patients in Madiun City rank fourth in the East Java region. . Objective: This research was conducted to determine the evaluation of the rationality of insulin in type 2 DM patients in the Outpatient Hospital of Madiun City Hospital for the period 2022. Methods: This research method is in the form of an observational research, retrospective data collection in the form of medical records of history of type 2 diabetes mellitus patients at Outpatient Hospital at RSUD Madison City. The total population in this study in the period January - December 2022 was 165 patients. Results: From the 62 type 2 DM patients who were outpatients at Madiun City Regional Hospital, it was found that 14.52% using single insulin and 12.90% used Detemir insulin. The use of the insulin combination was 85.48% and the Detemir – Aspart insulin combination was 58.06%. Conclusion: Evaluation of the rationality of insulin use showed that the correct drug was 100% and the correct dose was 93,55%.

Hereditary Amyloidosis: Insights Into a Fibrinogen A Variant Protein.

Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened the possibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet structure. Exploiting the comprehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine.

The european registry for patients with mechanical circulatory support (EUROMACS): fourth paediatric EUROMACS (Paedi-EUROMACS) report.

The use of ventricular assist devices in children is increasing. However, absolute numbers in individual centers and countries remain small. Collaborative efforts such as the Paedi-EUROMACS are therefore essential in order to combine international experience with paediatric ventricular assist devices. In this paper, the results from the fourth Paedi-EUROMACS report are presented. All paediatric (<19 years) patients supported by a ventricular assist device from the EUROMACS database were included. Patients are stratified into a congenital heart disease group and a group with a non-congenital aetiology. Endpoints included mortality, transplantation and recovery. Cox proportional hazard models were used to explore associated factors for mortality, cerebrovascular accident, and pump thrombosis. 590 primary implantations were included. The congenital group was significantly younger (2.5 versus 8.0 years respectively, p < 0.001) and were more commonly supported by a pulsatile flow device (73.5% vs 59.9%, p < 0.001). Mortality was significantly higher in the congenital group (30.8 vs 20.4%; p = 0.009) than in the non-congenital group. However, in multivariable analyses, congenital heart disease was not significantly associated with mortality (HR 1.285, CI 0.8111-2.036, p = 0.740). Pump thrombosis was the most frequently reported adverse event (377 events in 132 patients; 0.925 events per patient-year) and was significantly associated with BSA (HR 0.524 CI 0.333-0.823, p = 0.005), congenital heart disease (HR 1.641 CI 1.054-2.555, p = 0.028) and pulsatile flow support (HR 2.345 CI 1.406-3.910, p = 0.001) in multivariable analyses. This fourth Paedi-EUROMACS report highlights the increasing use of paediatric ventricular assist devices. The patient populations with congenital and non-congenital aetiology exhibit distinct characteristics and clinical outcomes.

Skin Lesion Prediction and Classification Using Innovative Modified Long Short-Term Memory-Based Hybrid Optimization Algorithm

Identification of pigmented skin lesions is necessary for the detection of severe diseases associated with the skin organ, notably malignancy. Accurate skin cancer diagnosis can be improved with the use of image detection approaches and computer classification skills. Therefore, this research work plans to perform skin lesion prediction and classification using a novel deep learning methodology. Initially, the data related to the skin lesion are gathered from the ISIC dataset. After collecting the images, the pre-processing is performed using hair removal and filtering hair removed images via median filtering. These pre-processed images undergo segmentation process accomplished using the U-Net method. Next, the features are extracted from these segmented images with the help of color features, and texture features by GLCM and RGB histogram features. These extracted features undergo the prediction phase that is accomplished using the MLSTM model, in which the parameter optimization is done by the nature inspired novel hybrid metaheuristic algorithm referred as SC-STBO algorithm with the consideration of accuracy maximization and RMSE minimization as the major fitness for the objective function. If the predicted output is returned as the presence of skin lesion, the same novel MLSTM model classifies the final skin lesion output into seven types, such as Vascular Lesions, Melanocytic Nevi, Melanoma, Dermatofibroma, Benign Keratosis-like Lesions, BCC, and Actinic Keratoses, respectively. Seven groups of skin diseases can be identified early thanks to the suggested effort, which can then be tested and properly handled by medical professionals. With an accuracy of 0.9931, the recommended methodology clearly outperforms traditional techniques. Similarly, the suggested methodology clearly beats the conventional methods, with a recall of 0.9825.

Safety and efficacy of deoxycytidine/deoxythymidine combination therapy in POLG-related disorders: 6-month interim results of an open-label, single arm, phase 2 trial

DNA polymerase gamma (POLG)-related disorders are a group of rare neurodegenerative mitochondrial diseases caused by pathogenic variants in POLG, the gene encoding POLG. Patients may experience a range of signs and symptoms, including seizures, vision loss, myopathy, neuropathy, developmental impairment or regression, and liver failure. The diseases follow a progressive, degenerative course, with most affected individuals dying within 3 months-12 years of diagnosis. At present, there are no effective treatments for POLG-related disorders. In this study we report the interim 6-month data from a long term open-label, single arm phase 2 trial, in which we assessed the safety and efficacy of combination therapy with deoxycytidine and deoxythymidine (dC/dT) in children with POLG-related disorders. dC/dT was given enterally in powder form, dissolved in water. The primary outcome measures included Newcastle Mitochondrial Disease Scale (NMDS) score, serum growth differentiation factor 15 (GDF-15; a biomarker of mitochondrial dysfunction), electroencephalography (EEG), seizure diary, and blood and urine tests to assess end organ and mitochondrial function. Secondary outcome measures included recording of all adverse events to evaluate the safety of the intervention. The trial is registered with ClinicalTrials.gov, NCT04802707 (https://clinicaltrials.gov/ct2/show/NCT04802707). Data were collected from 14 October, 2021 to 13 December,2023. We present 6-month interim data from the first ten people with POLG-related disorders enrolled in the trial, six with Alpers-Huttenlocher syndrome, two with ataxia-neuropathy spectrum, and two who do not fit into a classical POLG-related phenotype. During the 6 months of treatment, NMDS score improved from a mean of 27.3at baseline to 20.7at 6 months (estimated difference 6.0; 95% CI 2.5-∞). GDF-15 values remained stable or decreased in all patients; the mean decreased from 1031pg/ml to 729pg/ml (estimated difference 200; 95% CI 12-∞). 8/10 patients had abnormal baseline EEG; improvement in EEG was seen in 5 of these 8. There were no significant changes in other blood and urine testing. Regarding adverse events, two patients experienced diarrhea that spontaneously resolved. dC/dT is a promising treatment option for people with POLG-related disorders. Further research is needed to assess the long-term safety and efficacy in POLG-related disorders, as well as safety and efficacy in other mitochondrial DNA depletion disorders. This study was primarily funded by the Liam Foundation, with additional funding from the Savoy Foundation, Grand Défi Pierre Lavoie Foundation, and Fonds de Recherche du Québec - Santé.

Social acceptance of people with chronic diseases

The discussion concerns social acceptance of people with chronic diseases, covering the definition of acceptance, its determinants, stereotypes, and groups of diseases that most often face social reluctance. Social acceptance is a key element of healthy social functioning and implies agreement that people with chronic diseases exist, are respected and treated equally with healthy people. It is a process dependent on education, personal experience, social support and culture. Research indicates that people with mental illness, HIV/AIDS, skin diseases and obesity often experience stigma and discrimination. In particular, people with mental illnesses face negative stereotypes, such as being seen as dangerous and unable to function in society. People living with HIV/AIDS are often victims of social ostracism due to fear of infection and moral judgments. Skin diseases such as psoriasis and obesity also lead to social isolation and discrimination. Another group is people with cancer, who often experience social resentment due to fear, ignorance and stereotypes associated with the disease. Social education and psychological and social support are key to reducing stigma and improving the quality of life for these people. Practical measures to increase social acceptance include: educational programs, media campaigns, psychological support, legislative changes, and local and community initiatives. All of these activities can help reduce stigma and discrimination against people with chronic diseases, promoting greater empathy and understanding in society.

Impact of peroral endoscopic myotomy on the endoscopic pressure study integrated system.

The endoscopic pressure study integrated system (EPSIS) is an endoscopic diagnostic system utilized for evaluation of lower esophageal sphincter function. Although previous studies have determined that EPSIS was effective as a tool for the diagnosis of achalasia, it remains uncertain if EPSIS can detect significant changes before and after peroral endoscopic myotomy (POEM), which is the premier treatment for achalasia. This study aimed to evaluate the effectiveness of EPSIS as an objective diagnostic tool for assessing the clinical effect of POEM. We conducted a retrospective analysis of patients who underwent POEM from January 2022 to December 2023. The patients underwent EPSIS preoperatively and 2 months postoperatively. Intragastric pressure (IGP) parameters, including the maximum IGP, IGP difference, and waveform gradient were compared pre- and post-POEM. These parameters also were compared between two groups: the postoperative gastroesophageal reflux disease (GERD) group and the non-GERD group. A total of 50 patients were analyzed. The mean maximum IGP was significantly lower postoperatively than preoperatively (15.0 mmHg vs. 19.8 mmHg, P < 0.001). The mean IGP difference and waveform gradient were also significantly lower postoperatively than preoperatively (8.0 mmHg vs. 12.2 mmHg, P < 0.001; and 0.26 mmHg/s vs. 0.43 mmHg/s, P < 0.001, respectively). The mean postoperative waveform gradient was significantly lower in the GERD group (17 patients, 34%) than in the non-GERD group (33 patients, 66%) (0.207 mmHg vs. 0.291 mmHg, P = 0.034). The results supported the use of EPSIS as an effective diagnostic tool for assessing the effect of POEM.

Interstitial Lung Diseases and Non-Small Cell Lung Cancer: Particularities in Pathogenesis and Expression of Driver Mutations.

Interstitial lung diseases are a varied group of diseases associated with chronic inflammation and fibrosis. With the emerging and current treatment options, survival rates have vastly improved. Having in mind that the most common type is idiopathic pulmonary fibrosis and that a significant proportion of these patients will develop lung cancer as the disease progresses, prompt diagnosis and personalized treatment of these patients are fundamental. The scope of this review is to identify and characterize molecular and pathogenetic pathways that can interconnect Interstitial Lung Diseases and lung cancer, especially driver mutations in patients with NSCLC, and to highlight new and emerging treatment options in that view. Common pathogenetic pathways have been identified in sites of chronic inflammation in patients with interstitial lung diseases and lung cancer. Of note, the expression of driver mutations in EGFR, BRAF, and KRAS G12C in patients with NSCLC with concurrent interstitial lung disease is vastly different compared to those patients with NSCLC without Interstitial Lung Disease. NSCLC in patients with Interstitial Lung Disease is a challenging diagnostic and clinical entity, and a personalized medicine approach is fundamental to improving survival and quality of life. Newer anti-fibrotic medications have improved survival in IPF/ILD patients; thus, the incidence of lung cancer is going to vastly increase in the next 5-10 years.