Complex Disease Research Articles

Primary pulmonary alveolar soft part sarcoma with ASPSCR1-TFE3 gene fusion: Case report and literature review.

Primary pulmonary alveolar soft part sarcoma (ASPS) is an extremely rare disease characterized by a specific genetic abnormality - the ASPSCR1-TFE3 gene fusion. This study presented a 27-year-old male patient who experienced persistent chest tightness for over 6 months. The computed tomography (CT) scan and enhanced CT scan revealed a mass in the medial segment of the right middle lobe of his lung. The patients then underwent further diagnosis. Pathological examination showed the tumor to be consisting of polygonal cells with abundant eosinophilic or transparent cytoplasm arranged in nests. Next-generation sequencing reported ASPSCR1-TFE3 gene fusion, confirming the final diagnosis of primary pulmonary ASPS. Regular follow-ups of 12 months showed no signs of tumor recurrence. The patients underwent the medial segment resection of the right middle lobe for treatment. A CT examination 3 months after the operation showed that the patient had improved. The last review showed no recurrence or metastasis. This case report highlights the importance of detailed diagnosis, prompt treatment, and close monitoring of patients with ASPS.

Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer.

Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma (ESCC). These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci (eQTL) have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.

Lactucin ameliorates FFA-induced steatosis in HepG2 cells by modulating mitochondrial homeostasis through the SIRT1/PGC-1α signaling axis

Nonalcoholic fatty liver disease is a complex disease involving abnormal liver metabolism. Its strong association with metabolic dysfunction has led to a change in nomenclature to metabolism dysfunction-associated fatty liver disease (MAFLD). MAFLD pathogenesis involves abnormal accumulation of hepatic lipids that lead to the production of excess free fatty acids (FFAs), which in turn cause an imbalance in hepatic mitochondrial function. Lactucin, a natural compound extracted from Cichorium glandulosum Boiss. et Huet, regulates liver metabolism and protects the liver. However, the potential mechanisms underlying the lactucin-mediated effects in MAFLD require further investigation. In the present study, HepG2 cells were treated with FFAs to establish an in vitro model of MAFLD. Parameters related to lipid accumulation and mitochondrial function, including triglycerides (TG), oil red O-stained lipid droplets, reactive oxygen species (ROS), mitochondrial membrane potential (JC-1), adenine triphosphate (ATP), and complex III were analysed. Morphology of the mitochondria were evaluated by transmission electron microscopy. Furthermore, key proteins in the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signalling axis and mitochondrial quality control were analysed. The SIRT1 inhibitor EX-527 was used to verify the key role of the SIRT1 signalling pathway. Western blotting showed that lactucin upregulated the expression of SIRT-1, PGC-1α, Nrf1, Tfam, Mfn2, and Opa1, and promoted mitochondrial biosynthesis and kinetics. The results suggest that lactucin restores mitochondrial dynamic homeostasis by upregulating the SIRT1/PGC-1α signalling axis, thereby reducing FFA-induced lipid accumulation in HepG2 cells.

Synergistic effects of curcumin and stem cells on spinal cord injury: a comprehensive review.

Spinal cord injury (SCI) is damage to the spinal cord that permanently or temporarily disrupts its function, causing considerable autonomic, sensory, and motor disorders, and involves between 10 and 83 cases per million yearly. Traumatic SCI happens following primary acute mechanical damage, leading to injury to the spinal cord tissue and worsening clinical outcomes. The present therapeutic strategies for this complex disease fundamentally rely on surgical approaches and conservative remedies. However, these modalities are not effective enough for neurological recovery. Therefore, it is necessary to discover more efficient methods to treat patients with SCI. Today, considerable attention has been drawn to bioactive compounds-based remedies and stem cell therapy for curing various ailments and disorders, such as neurological diseases. Some researchers have recommended that harnessing curcumin, a polyphenol obtained from turmeric, in combination with stem cells, like mesenchymal stem cells, neural stem cells, and ependymal stem cells, can remarkably improve neurological recovery-related parameters more effective than the treatment with these two methods separately in experimental models. Hereby, this literature review delves into the functionality of curcumin combined with stem cells in treating SCI with a focus on cellular and molecular mechanisms.

Incidence, diagnostics, therapeutic management and outcomes of paediatric intestinal pseudo-obstruction in the Netherlands: A 20-year retrospective cohort study.

To describe incidence, clinical course, diagnostic and therapeutic management and long-term follow-up of paediatric intestinal pseudo-obstruction (PIPO) in the Netherlands between 2000 and 2020. Multicenter, national, retrospective, observational study including patients aged <18 years diagnosed with PIPO and treated between 2000 and 2020 in Dutch academic medical centres. Outcomes included demographics, incidence, symptoms, diagnostic- and treatment methods used during follow-up, number of hospital admissions and mortality. Between 2000 and 2020, 43 children (median age 120 months, range 13 - 301, 54% female) were diagnosed with PIPO in the Netherlands. Mean incidence was 0.008/100,000/years (range 0/100 000-0.029/100 000). Twenty-six patients developed PIPO in the neonatal period. Initial symptoms were vomiting (n = 21/35, 60%) and abdominal distension (n = 14/35, 40%). Diagnostic strategies included imaging, manometry, histopathology, metabolic- and genetic screening, endoscopy and exploratory surgery. Treatment was divided in nutritional support, pharmacotherapy, colonic irrigation and surgical interventions, of which nutrition and surgery were the cornerstones for care. During the observed study period, the median number of hospital admissions was 22.5 (range 1-176) with a median of 157.5 days (range 3-840) during 20-year follow-up. Two patients (6%) died: one from sepsis and one due to a severe underlying neurological disease. Heterogeneity in diagnostic- en treatment methods existed between patients. PIPO is a rare, long-lasting complex disease requiring a high number of diagnostic and therapeutic interventions and hospital admissions. However, mortality rate is relatively low. Based on our results, we recommend centralization and standardization of care for this complex rare disease.

GREMI: An Explainable Multi-Omics Integration Framework for Enhanced Disease Prediction and Module Identification.

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort.

Opportunistic genomic screening has clinical utility: An interventional cohort study

Practice is shifting toward genome-first approaches, such as opportunistic screening for secondary findings (SFs). Analysis of SFs could be extended beyond medically actionable results to include non-medically actionable monogenic disease risks, carrier status, pharmacogenomic variants, and risk variants for common complex disease. However, evidence on the clinical utility of returning these results is lacking. We assessed the outcomes of opportunistic screening for a broad spectrum of SFs by evaluating the yield, impact on clinical management, and consistency between SFs and participants' clinical features and family history. Adult cancer patients had GS with the option to learn multiple categories of SFs. Outcomes data were collected through chart review and participant-reported measures up to one year after return of results. All participants (n=139, 85.6% female, average 54.6 years old) who elected to learn SFs had ≥1 variant reported (100% [139/139]). The yield of reportable findings was highest for pharmacogenomic variants (97.8% [135/138] of participants), followed by common disease risk variants (89.4% [118/132]), carrier status (89.3% [117/131]), and variants related to Mendelian (27.2% [34/125]), medically actionable (15.2% [21/138]), and early-onset neurodegenerative (2.6% [3/117]) disease risks. SFs from the ACMG list (v3.2, non-cancer genes) were reported in 1.4% (2/138) of participants. SFs across all categories demonstrated clinical utility by prompting management changes in 28.1% (39/139) of participants. Moreover, a considerable proportion of participants had suggestive clinical features (49.0% (24/49)]) or family history (21.8% (27/124)) potentially related to their SFs. Our findings indicate there are potential benefits from opportunistic screening for a broad range of SFs.

Uncovering Disease Mechanisms through AI and Visual Computing: A Multi-Scale Approach to Biological Data Interpretation

This research focuses on uncovering complex disease mechanisms by employing artificial intelligence (AI) and visual computing to interpret multi-scale biological data. By analyzing data from molecular to organ-level systems, this study aims to bridge the gap between cellular insights and clinical applications, offering new perspectives on diseases such as cancer, neurodegenerative disorders, and cardiovascular diseases. Through a comprehensive approach to data integration, the project compiles omics and imaging data to enable holistic analysis across biological scales. The use of hierarchical neural networks, graph neural networks (GNNs), and convolutional neural networks (CNNs) allows for multi-dimensional modeling and the extraction of disease-related patterns. The findings are validated with clinical data to support actionable insights, laying the groundwork for personalized disease models and precision therapeutic strategies. Expected outcomes include breakthroughs in disease understanding, advancements in precision medicine, and the establishment of a robust AI framework that will contribute to future biomedical applications. This multidisciplinary approach promises to transform diagnostics, prognosis, and treatment, facilitating a deeper understanding of disease mechanisms and their translation into clinical practice. The integration of multi-scale data enables a nuanced view of disease, capturing interactions that may be obscured in single-level analyses. By employing advanced visual computing techniques, the project highlights structural abnormalities within tissue samples, linking cellular changes to systemic disease pathways. This approach not only aids in identifying novel biomarkers but also supports the development of individualized treatment models that predict patient-specific responses. With validation from clinical datasets, the AI framework is poised to enhance clinical decision-making, offering insights tailored to the unique biological profiles of patients. The project’s multi-scale methodology serves as a foundation for future biomedical research, setting a new standard for AI-driven disease analysis.

Advancements in Engineering Tetrahedral Framework Nucleic Acids for Biomedical Innovations.

Tetrahedral framework nucleic acids (tFNAs) are renowned for their controllable self-assembly, exceptional programmability, and excellent biocompatibility, which have led to their widespread application in the biomedical field. Beyond these features, tFNAs demonstrate unique chemical and biological properties including high cellular uptake efficiency, structural bio-stability, and tissue permeability, which are derived from their distinctive 3D structure. To date, an extensive range of tFNA-based nanostructures are intelligently designed and developed for various biomedical applications such as drug delivery, gene therapy, biosensing, and tissue engineering, among other emerging fields. In addition to their role in drug delivery systems, tFNAs also possess intrinsic properties that render them highly effective as therapeutic agents in the treatment of complex diseases, including arthritis, neurodegenerative disorders, and cardiovascular diseases. This dual functionality significantly enhances the utility of tFNAs in biomedical research, presenting valuable opportunities for the development of next-generation medical technologies across diverse therapeutic and diagnostic platforms. Consequently, this review comprehensively introduces the latest advancements of tFNAs in the biomedical field, with a focus on their benefits and applications as drug delivery nanoplatforms, and their inherent capabilities as therapeutic agents. Furthermore, the current limitations, challenges, and future perspectives of tFNAs are explored.

Repercussion of Primary Nucleation Pathway: Dementia and Cognitive Impairment.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and prion disease, are characterized by the conversion of normally soluble proteins or peptides into aggregated amyloidal fibrils. These diseases result in the permanent loss of specific types of neurons, making them incurable and devastating. Research on animal models of memory problems mentioned in this article contributes to our knowledge of brain health and functionality. Neurodegenerative disorders, which often lead to cognitive impairment and dementia, are becoming more prevalent as global life expectancy increases. These diseases cause severe neurological impairment and neuronal death, making them highly debilitating. Exploring and understanding these complex diseases offer significant insights into the fundamental processes essential for maintaining brain health. Exploring the intricate mechanisms underlying neurodegenerative diseases not only holds promise for potential treatments but also enhances our understanding of fundamental brain health and functionality. By unraveling the complexities of these disorders, researchers can pave the way for advancements in diagnosis, treatment, and ultimately, improving the lives of individuals affected by neurodegenerative diseases.

DETERMINATION OF THE AMOUNT OF POLYPHENOLS IN THE FOOD SUPPLEMENT "ASBOSIM" USED IN THE TREATMENT OF HYPERTENSION DISEASE

It is known that one of the diseases that are difficult to treat in modern medicine is an increase in blood pressure, i.e. hypertension. Hypertension is a pathology of the cardiovascular system, a complex disease characterized by an increase in arterial pressure, followed by organomorphological changes. Hypertension is mainly caused by constant nervousness, depression and stress, increased amount of adrenaline in the blood, alcohol consumption, excessive obesity and other factors. This disease is one of the main diseases that lead to complications such as myocardial infarction, stroke, heart attacks, and heart and kidney failure. The main symptoms of high blood pressure are headache, dizziness, ringing in the ears and heart failure. High blood pressure is more common in middle-aged and elderly people.

Knowledge, Attitude and Practice of Conventional Medicine Among Thalassaemia In Malaysia: Conceptual paper

Thalassaemia is chronic hereditary blood disorder. Medication has extended patients' lifespans, but research on their quality of life is scarce due to psychological impacts and medication adherence issues. The objective is to develop and validate a survey assessing the knowledge, attitude, and practice of Malaysian thalassaemia patients towards medication. We will use an exploratory mixed-methods approach with ethical approval from UiTM. Phase I involves semi-structured interviews with thalassaemia patients. Phase II focusses on creating and validating KAP instruments with expert panels and pilot testing. The tools will help medical professionals gather data to improve treatment compliance.

Pathogenesis of thoracic ossification of the ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) is characterized by ectopic ossification of the ligamentum flavum in the thoracic spine and is considered the main cause of thoracic spinal stenosis and spinal cord disease. Osteoblast specific transcription factor Osterix (Osx) is required for bone formation, and there is no bone formation or ossification without Osx. Surgical intervention is recognized as the only effective method for TOLF treatment with set of complications. However, underlying mechanisms of TOLF are not well understood. This paper summarizes the pathogenesis of TOLF. Some relevant factors have been discussed, such as mechanical stress, genetic susceptibility genes, endocrine and trace element metabolism abnormalities, which may associate with TOLF. More recent studies using proteomics technology and RNA sequencing approach have discovered that some new factors participate in TOLF by upregulation of Osx gene expression including inflammatory factors. TOLF is a unique disease involving multiple factors. On the other hand, studies on TOLF pathogenic mechanism may provide new ideas for finding possible upstream regulatory factors of Osx and further developing novel drugs to stimulate new bone formation to treat osteoporosis.

Infiltrations of plasma cells in synovium predict inadequate response to Adalimumab in Rheumatoid Arthritis patients

ObjectiveRheumatoid arthritis (RA) is a clinically heterogeneous and complex autoimmune disease, making the prediction of therapeutic responses a significant challenge. This study aims to assess the role of clinical and synovial biomarkers in predicting poor response to adalimumab treatment in RA patients.MethodsThis single-center prospective study included 56 RA patients who had an inadequate response to methotrexate (MTX). At baseline, comprehensive assessments including complete blood count, liver and kidney function tests, blood glucose levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), as well as counts of swollen and tender joints, Health Assessment Questionnaire (HAQ) score, pain visual analogue scale (VAS) scores, and DAS28-CRP scores were conducted. Synovial biopsies were performed, followed by an efficacy evaluation at 12 weeks of adalimumab treatment. Patients not meeting the ACR20 criteria were classified into the non-responder group, with the remainder categorized as the responder group.ResultsOut of the participants, 24 (42.9%) failed to achieve ACR20 with adalimumab treatment. Non-responders exhibited higher infiltration of plasma cells in the synovium. Multivariate logistic regression analysis identified the presence of plasma cells as an independent risk factor for inadequate response to adalimumab.ConclusionInadequate responses to adalimumab in RA patients were associated with increased plasma cell infiltrations in the synovium. These findings suggest a promising target for tailored therapies in rheumatoid arthritis.

Exome Profiling Suggests Combined Effect of Myeloperoxidase, Toll-Like Receptors, and Metallopeptidase in Hidradenitis Suppurativa

Background: Hidradenitis suppurativa, also called acne inversa, is a chronic skin inflammatory condition involving hair follicles, sebaceous glands, and apocrine glands. Symptoms can be variable in intensity, ranging from mild to severe. The exact causes of hidradenitis suppurativa are not fully understood, but the etiology is presumed to be multifactorial, encompassing genetics and environmental factors. Methods: Two families presented with hidradenitis suppurativa with an autosomal dominant pattern. We performed whole-exome sequencing in two unrelated patients from the two families. Results: We identified two and three variants in the two families, respectively. Variants involved the TLR2 and MPO genes in the first family and the MMP2, GJB2, and TLR4 genes, some of which have already been previously reported as possible candidates for hidradenitis suppurativa. Conclusion: It is very likely that variants in a single gene only rarely cause the condition and that most cases, especially familial hidradenitis suppurativa cases, may more probably take the form of polygenic disorders.

Neurofibroma-like Desmoplastic Melanoma: A Series of Five Cases Exploring the Role of Molecular Testing as a Diagnostic Adjunct and Highlighting the Differential Diagnosis With Diffuse-type Neurofibroma.

A subset of desmoplastic melanomas (DMs) can show extensive morphologic and immunohistochemical overlap with cutaneous diffuse-type neurofibroma. Neurofibroma-like desmoplastic melanoma (NFLDM) thus poses a significant diagnostic pitfall because the clinical implications of these 2 entities differ dramatically. A series of 17 DMs, including 5 cases of NFLDM, were compared with a cohort of 53 cutaneous diffuse-type neurofibromas to explore the utility of molecular testing in the differential diagnosis between NFLDM and neurofibroma and to determine potentially useful morphologic features in this differential diagnosis. Unlike NFLDM, cutaneous diffuse-type neurofibromas: (1) rarely feature intratumoral or peritumoral lymphoid aggregates, (2) consistently harbor an intrinsic stromal support vasculature composed of evenly spaced capillary-sized vessels, and (3) infiltrate adjacent adipose tissue in a dermatofibrosarcoma protuberans-like manner with a complete lack of chronic inflammation or fat necrosis at the leading edge of the tumor. Conversely, DMs, including NFLDM: (1) do not contain Wagner-Meissner bodies, (2) often induce fat necrosis and/or chronic inflammation at the interface with adjacent fibroadipose tissue, (3) lack the intrinsic capillary-sized stromal vasculature observed in most neurofibromas, and (4) may harbor foci of perineuriomatous differentiation, mimicking a hybrid nerve sheath tumor. Any deviation from the expected clinical or morphologic features of cutaneous diffuse-type neurofibroma should raise suspicion for NFLDM. Although not entirely sensitive or specific, molecular testing can help to support the diagnosis of NFLDM by demonstrating genetic abnormalities associated with melanoma, including a UV-light-induced mutational signature, high tumor mutational burden, and/or chromosomal copy number alterations typical of melanoma.

Comparison of Short Fast Fourier Transform and Continuous Wavelet Transform in Study of Stride Interval

Neurodegenerative diseases (NDD) are a heterogeneous group of complex diseases characterized by neuronal loss and progressive degeneration of different areas of the nervous system. Gait analysis presents an early recognition system for NDD which is important to increase the patient’s awareness of their health conditions. However, it is very difficult to identify and formulate suitable digital biomarkers from the data collected from gait experiments such as stride interval and swing. The objective of this paper is to compare the result of Short - Time Fourier Transform (STFT) and Continuous Wavelet Transform (CWT) on the collected stride interval of healthy young people and healthy old people. In this paper, STFT and CWT are performed on the collected stride interval and from the result of the STFT and CWT, further features are extracted like instantaneous RMS and maximum RMS value. STFT is performed on the collected stride interval from a window length of 64 to 512 while CWT is performed on the collected stride interval from the scale of 128 to 2048. The processing time of the STFT and CWT with varied window lengths and scales respectively are collected. Besides, the actual maximum time from the time - frequency plot derived from STFT and CWT is also collected. Both STFT and CWT show that the young group has a higher maximum RMS, an indication of higher stride interval than the old group and higher variance, an indication of higher gait complexity. The suitable window lengths for STFT in analyzing the stride interval are 64 and 128 while the scale for CWT should be set to the lowest scale. Overall, STFT with a window length of 64 and 128 is better in analyzing the stride interval due to low processing time at the expense of slightly less accurate time - frequency representation.

AI predictive modeling of survival outcomes for renal cancer patients undergoing targeted therapy.

Renal clear cell cancer (RCC) is a complex disease that is challenging to predict patient outcomes. Despite improvements with targeted therapy, personalized treatment planning is still needed. Artificial intelligence (AI) can help address this challenge by developing predictive models that accurately forecast patient survival periods. With AI-powered decision support, clinicians can provide patients with tailored treatment plans, enhancing treatment efficacy and quality of life. The study analyzed 267 patients with renal clear cell carcinoma, focusing on 26 who received targeted drug therapy. The data was refined by excluding 8 patients without enhanced CT scans. The research team categorized patients into two groups based on their expected lifespan: Group 1 (over 3 years) and Group 2 (under 3 years). The UPerNet algorithm was used to extract features from CT tumor markers, validating their effectiveness. These features were then used to develop an AI-based predictive model trained on the dataset. The developed AI model demonstrated remarkable accuracy, achieving a rate of 93.66% in Group 1 and 94.14% in Group 2. In conclusion, our study demonstrates the potential of AI technology in predicting the survival time of RCC patients undergoing targeted drug therapy. The established prediction model exhibits high predictive accuracy and stability, serving as a valuable tool for clinicians to facilitate the development of more personalized treatment plans for patients. This study highlights the importance of integrating AI technology in clinical decision-making, enabling patients to receive more effective and targeted treatment plans that enhance their overall quality of life.

A multidimensional approach to the management of patients in prolonged weaning from mechanical ventilation - the concept of treatable traits - a narrative review.

Background Established structured weaning approaches, which are effective for patients in simple and difficult weaning, are often not appropriate for patients undergoing prolonged weaning. Addressing the complexity of weaning failure requires personalized precision medicine. The therapeutic concept of Treatable Traits (TTs) has been proposed as a new paradigm for the management of chronic respiratory diseases. It is based on a multidimensional assessment of specific characteristics, which can be addressed by specific interventions that go beyond traditional diagnostic criteria. The concept is increasingly adopted for other complex diseases. Summary This is a narrative review and an expert opinion on the development of a concept of TTs for patients undergoing prolonged weaning. The proposed TTs are based on a systematic review of risk factors for prolonged weaning, an analysis of claims data to assess risk factors within 96 hours of IMV onset and data from the WEAN-SAFE study. A multidisciplinary team identified clinically important TTs and determined appropriate interventions. The following TTs have been identified: Airway disorders and complications associated with tracheostomy or intubation, such as airway obstruction, strictures or tracheomalacia, infectious aspects, anxiety, depression, delirium, post-traumatic stress disorder, anemia, pulmonary and cardio-renal disease. The multidimensional holistic approach also includes tailored sedation and pain management, nutritional therapy, early mobilization and physiotherapy. Key message We propose a framework of relevant considerations for a multidimensional approach to the management of patients undergoing prolonged weaning that supports the regain of respiratory capacity, reduces the respiratory load and thus could resolve the respiratory workload imbalance.

Lesions of the Palm – Mimickers of Dupuytren’s Disease

Background and Aims: Dupuytren’s contracture is a prevalent, hereditary fibroproliferative disorder affecting the palmar aponeurosis, which can resemble various neoplastic and non-neoplastic disorders of the hand. This resemblance poses a diagnostic challenge for healthcare professionals. This observational study aims to evaluate the range of conditions that can be mistaken for Dupuytren’s contracture over a 12-year period (2008–2020) at a specialised orthopaedic oncology centre. Materials and Methods: A retrospective analysis of palmar lesions referred to our tertiary orthopaedic oncology hospital was conducted. Data were gathered from oncology, radiology and histopathology databases. We specifically examined lesions located solely on the palmar aponeurosis, excluding the thenar and hypothenar regions. Patient demographics, clinical features, imaging results and clinical management outcomes were documented for descriptive analysis. Results: A total of 21 palmar lesions meeting the inclusion criteria were identified. The average age of the participants was 48 years (ranging from 3 to 69 years). There was no significant difference in gender distribution, with 11 females and 10 males represented in the cohort. The majority of the identified lesions were benign tumours (16), with one case of malignant rhabdomyosarcoma. Among the benign tumours, lipomas were the most common ( n = 5). Other benign tumours included three neurofibromas, a schwannoma, a granuloma, a ganglion cyst, a giant cell tumour (GCT), an angiomyxoma, a myofibroma, a cavernous haemangioma, a non-specific fibrovascular lesion and four additional non-neoplastic lesions. Conclusion: A variety of benign, malignant or neoplastic conditions of the hand can closely resemble Dupuytren’s contracture, particularly in the initial stages of their development. A thorough clinical examination, combined with a high level of suspicion, along with supplementary investigations and histopathological analysis, is essential for accurate diagnosis and effective management of patients.