Stage Of Disease Research Articles

Diet-microbiome interactions influence lung function in chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) affects 30 million Americans. Previous epidemiologic work has shown that diet can impact pulmonary function in those with and without COPD. Diet is also a major driver of gut microbiome composition and function. Importantly, the gut microbiome has also been associated with lung health (i.e., the gut-lung axis) in both preclinical and clinical studies. Despite this growing body of evidence, many questions remain regarding the gut-lung axis. Specifically, how the microbiome impacts the relationship between diet factors and spirometry or stage of disease in people with COPD is little understood. We hypothesize that there are taxonomic differences in the gut microbiome among the different stages of COPD and that diet microbiome interactions influence pulmonary function. This study aimed to identify how the GI microbiota correlated with the severity of respiratory disease in COPD patients and how the microbiome may mediate the relationship between diet, including fiber and omega-3 fatty acids, and lung function outcomes.

Hand therapy interventions for the prevention of chemotherapy-induced peripheral neuropathy of the hands in patients with pancreatic cancer

Abstract Background Chemotherapy-induced peripheral neuropathy (CIPN), a common problem, can impair function and quality of life in patients, potentially limiting chemotherapy and adversely affecting outcomes. Methods This trial compared investigational hand therapy intervention (Investigational) compared with a traditional occupational therapy approach (Traditional) to prevent CIPN in patients with pancreatic cancer receiving gemcitabine and albumin-bound paclitaxel containing regimens. Results forty-nine patients were enrolled with 40 evaluable for statistical analysis (21 Investigational/19 Traditional). CIPN in the hands was reported in 6 patients (28.6%) in Investigational, and 4 (21.1%) in Traditional P = .721. Kaplan-Meier analysis showed a mean time-to-event of 76.0 days (90% CI: 68.5, 83.6), and 75.8 (90% CI: 68.5, 83.2) days respectively, P = .614. Fifteen patients in each group (78.9% Traditional, 71.4% in Investigational) were censored as they did not develop CIPN. No correlation was found between CIPN risk and age, sex, BMI, disease stage, performance status, or chemotherapy dose. Conclusion Seventy-four percent of patients receiving gemcitabine, albumin-bound paclitaxel, and cisplatin did not develop CIPN of the hands by day 84. There was no statistical difference in time to onset of CIPN between the two groups. Early adaption of occupational therapy may prevent early onset CIPN in chemotherapy patients. ClinicalTrials.gov Identifier NCT05374876.

Identifying central dimensions of quality of life including life-related values, preferences and functional health in older patients with cancer: a scoping review protocol

BackgroundOlder patients with cancer already represent the largest proportion of cancer survivors which will further increase in the upcoming years. However, older patients are highly underrepresented in clinical research, leading to a detrimental knowledge gap. Research on important aspects of quality of life (QoL) and associated factors for older patients with cancer is insufficient to date.AimThe objective of this scoping review therefore is to investigate the dimensions of QoL including functional health, life-relevant values and preferences in older adults with cancer across all tumor entities and health care settings. It will further identify medical, sociodemographic, psychosocial and geriatric aspects associated with QoL in the elderly and compare these with younger cancer patients and older non-cancer cases.MethodsPublished articles investigating QoL dimensions and associated factors in older patients with cancer, i.e., exclusively patients ≥65 years or mean/median age ≥ 70 years for age-mixed samples, or that compare results of older with younger cancer patients or with older non-cancer cases will be considered for this scoping review. Older patients with cancer across all tumor entities, disease stages and health care setting will be included. PubMed and PsychINFO databases will be searched for relevant articles. Abstracts and titles will be screened for basic inclusion, and two independent reviewers will conduct a full text screening to evaluate the age criteria and decide on the final inclusion of the study. Data on study and participant characteristics, QoL dimensions and geriatric factors will be extracted using a data extraction sheet. Results will be summarized descriptively to address the objectives of this review.DiscussionThe findings of this scoping review will provide valuable insights into central dimensions of QoL, including values, preferences and functional health in older adults with cancer, and help to improve targeted interventions and healthcare planning.

The Detailed Analysis of Polish Patients with Non-Small Cell Lung Cancer Through Insights from Molecular Testing (POL-MOL Study)

Molecular testing is recommended in patients with metastatic non-small cell lung cancer (NSCLC), but the extent of its use in Poland is unknown. The aim of the POL-MOL study was to investigate the frequency of using molecular testing in Polish patients with NSCLC. The invited Polish oncologists completed two questionnaires, and data for 1001 patients undergoing systemic treatment for NSCLC were collected. The use of molecular tests for the following genetic mutations was recorded: EGFR (del19, sub21), EGFR (other than del19/sub21), EGFR T790M, ALK (expression and rearrangement), RET, NTRK, ROS1, BRAF, HER2, and MET, as well as for immunochemical assessment of programmed cell death ligand 1 (PD-L1). Thanks to the weighting procedure, the results are representative of the population of Polish patients treated for NSCLC. Molecular tests were applied in 78% of patients with NSCL, 70% of patients with NSCLC not otherwise specified, and in 12% of patients with squamous cell carcinoma of the lung. The frequency of application increased with disease stage in all groups. In patients with squamous cell carcinoma, approximately 30% of tests for EGFR, ALK, and RET mutations were positive, which confirms the importance of testing at least a preselected subgroup of patients.

Understanding depression, anxiety and stress in young people living with HIV in Ghana

Ghanaians with perinatally acquired human immunodeficiency virus (HIV) infection now live into adulthood. It is known that adolescents and young adults living with HIV have a high risk of mental health comorbidity. Despite increasing global attention on HIV–mental health interactions, the field remains understudied in Ghana, with an attendant lack of national integrated care solutions. This study aimed to measure the burden and explore the context of depression, anxiety and stress symptoms among young people living with HIV receiving care at a tertiary care hospital in Ghana. This was an explanatory sequential mixed-methods study. Depression, anxiety and stress symptoms were measured using the Depression, Anxiety and Stress Scale, and their associations with quality of life (QoL), socioeconomic status, internalised stigma, disease stage and HIV-related risk-taking behaviours were explored. After preliminary quantitative data analysis, semi-structured interviews were conducted for those who screened positive for depression and/or anxiety to explore their experience with this comorbidity. This study found a low prevalence of depression and anxiety symptoms, which were associated with higher stigma scores and lower QoL. We believe this low prevalence to be attributable to the effect of several psychosocial interventional programmes, which were previously piloted with the study cohort that have gradually normalised mental health discussions. Participants also showed marked resilience and knowledge about their condition. The results of this study present an opportunity to advocate and scale up effective locally adapted and strength-based solutions to address the mental illness–HIV syndemic in Ghanaian young people living with HIV.

Differences in setting of initial dementia diagnosis among fee-for-service Medicare beneficiaries.

Accurate and timely diagnosis of dementia is necessary to allow affected individuals to make informed decisions and access appropriate resources. When dementia goes undetected until a hospitalization or nursing home stay, this could reflect delayed diagnosis or misdiagnosis, and may reflect underlying disparities in healthcare access. In this retrospective cohort study, we used 2012-2020 Medicare claims and other administrative data to examine variation in setting of dementia diagnosis among fee-for-service Medicare beneficiaries with an initial claims-based dementia diagnosis in 2016. We used multinomial logistic regression to evaluate the association of person and geographic factors with diagnosis location, and Cox proportional hazards regression to examine 4-year survival relative to diagnosis location. Among 754,204 Medicare beneficiaries newly diagnosed with dementia in 2016, 60.3% were diagnosed in the community, 17.2% in hospitals, and 22.5% in nursing homes. Adjusted 4-year survival rates were significantly lower among those diagnosed in hospitals [-16.1 percentage points (95% CI: -17.0, -15.1)] and nursing homes [-16.8 percentage points (95% CI: -17.7, -15.9)], compared to those diagnosed in the community. Community-diagnosed beneficiaries were more often female, younger, Asian or Pacific Islander, Native American or Alaskan Native, Hispanic, had fewer baseline hospitalizations and higher homecare use, and resided in wealthier ZIP codes. Rural beneficiaries were more likely to be diagnosed in hospitals. Many older adults are diagnosed with dementia in a hospital or nursing home. These individuals have significantly lower survival than those diagnosed in the community, which may indicate diagnosis during an acute illness or care transition, or at a later disease stage, all of which are suboptimal. These results highlight the need for improved dementia screening in the general population, particularly for individuals in rural areas and communities with higher social deprivation.

Non-Invasive Ultrasound Diagnostic Techniques for Steatotic Liver Disease and Focal Liver Lesions: 2D, Colour Doppler, 3D, Two-Dimensional Shear Wave Elastography (2D-SWE), and Ultrasound-Guided Attenuation Parameter (UGAP).

We conducted a comprehensive literature review to evaluate the efficacy of combining two-dimensional shear wave elastography (2D-SWE) and ultrasound-guided attenuation parameter (UGAP) in assessing the risk of progressive metabolic dysfunction-associated steatohepatitis (MASH). This narrative review explores the applications of liver ultrasound in diagnosing metabolic liver diseases, focusing on recent advancements in diagnostic techniques for steatotic liver disease (SLD). Liver ultrasound can detect a spectrum of SLD manifestations, from metabolic dysfunction-associated liver disease (MASLD) to fibrosis and cirrhosis. It is also possible to identify inflammation, hepatitis, hepatocellular carcinoma (HCC), and various other liver lesions. Innovative ultrasound applications, including elastography and UGAP, can significantly enhance the diagnostic capabilities of ultrasound in accurately interpreting liver diseases. Understanding the pathogenesis of liver diseases requires a thorough analysis of their etiology and progression in order to develop sound diagnostic and therapeutic approaches. Chronic liver diseases (CLD) vary in origin, with MASLD affecting approximately 20-25% of the general population. The insidious progression of CLD from inflammation to fibrosis and cirrhosis underscores the need for effective early detection methods. This review aims to highlight the evolving role of non-invasive ultrasound-based diagnostic tests in the early detection and staging of liver diseases. By synthesizing current evidence, we aim to provide an updated perspective on the utility of advanced ultrasound techniques in redefining the diagnostic landscape for metabolic liver diseases.

Features of the course of the new coronavirus infection COVID-19 in chronic kidney disease

Purpose of the study. Study of the characteristics of the course of the new coronavirus infection COVID-19 in chronic kidney disease (CKD). Materials and methods. A total of 182 patients who were in the State Budgetary Institution “Emergency Medical Care Hospital” (Cheboksary) with a confirmed diagnosis of COVID-19 were examined. Results. A high incidence of CKD in hospitalized patients is shown. In CKD, there is a high mortality from COVID-19, statistically significant for CKD stage 3, but not for CKD stages 1-2. A number of clinical and laboratory parameters associated with an increased risk of adverse outcome have been identified. CKD is an independent risk factor that increases the risk of death when combined with these parameters. The positive effect of Janus kinase inhibitors is reflected when they are prescribed in the group under 65 years of age and in the first days of patient admission. Conclusion. The results of the study indicate the necessity of studying kidney function in patients with a new coronavirus infection. Patients with chronic kidney disease stages 3-4 require close dynamic monitoring as a risk group for severe disease, affecting survival.

The effect of coaching on health information literacy in patients with chronic kidney disease: a randomized controlled trial

BackgroundSince chronic kidney disease is highly insidious in the early stages, most diagnosed patients have already developed irreversible renal failure. There is a lack of effective implementation and standardization of health education management for patients with chronic kidney disease, and the impact of health education management on health information literacy is not yet known.MethodsThis randomized controlled clinical trial was conducted from March 2022 to March 2023. A total of 130 patients with chronic kidney disease stage 3–4 were selected from a tertiary hospital in Zhuhai via a convenience sampling method and were then randomly assigned to intervention and control groups. The Health Information Literacy Questionnaire for Chronic Kidney Disease was used to assess the health literacy of the patients at month 0 and month 12. In addition, the renal function-related indices of the patients were measured before and after the intervention. The study adhered to SPIRIT guidelines.ResultsThere was no significant difference between the two groups in health information literacy, platelet count, estimated glomerular filtration rate, or albumin level. However, the intervention group showed a significant improvement in health behavioral status such as information acquisition, checkups, and physical activity. Subgroup analysis revealed that hemoglobin was significantly higher in non-employed patients than in the intervention group. There was a significant improvement in hemoglobin level after receiving health guidance in patients with intermediate education, and acquisition capacity and estimated glomerular filtration rate in the intervention group were lower than in the control group for patients with elementary education.ConclusionReceiving health coaching helped to improve self-management behaviors and hemoglobin levels of patients with stage 3–4 chronic kidney disease. Education level is an important factor influencing the effectiveness of health coaching techniques.Trial registrationThis study was prospectively registered in the China Clinical Trial Registry on November 10, 2021, with registration number: ChiCTR2100053103.

Medication Use and Treatment Indications in Huntington's Disease; Analyses from a Large Cohort.

Huntington's Disease is a rare neurodegenerative disorder in which appropriate medication management is essential. While many medications are prescribed based on expert knowledge, overviews of actual medication use in HD are sparse. We provide a detailed overview of medication use and associated indications across HD disease stages, considering sex and regional differences. Data from the largest observational HD study, ENROLL-HD, were used. We created HD-related medication and indication classes to identify medication trends in manifest, premanifest and control subjects. We studied medication use in adult, childhood- and adolescent-onset HD, incorporating disease stage (including phenoconverters), sex and regional differences. In 8546 manifest HD patients, 84.6% used medication (any type), with the average number of medications per user rising from 2.5 in premanifest HD to 5.2 in end stage disease. Antipsychotics (29.2%), SSRIs (27.5%) and painkillers (21.8%) were most often used. Medication use varied with disease progression. Several differences were observed between the sexes, and notably between Europe and Northern America as well. Medication use increased after phenoconversion (from 64.8% to 70.6%, P < 0.05), with the largest difference in antipsychotic use (4.4%-7.8%, P < 0.05). Medication patterns were different in childhood-onset HD, with no use of painkillers, less use of anti-chorea and antidepressant drugs, and more for aggression and irritability. Medication use in HD increases with disease progression, with varying types of medications prescribed based on disease stage, sex, and region of living. Recognizing these medication trends is vital for further personalized HD management.

Dynamic tissue distraction may enhance therapeutic efficacy for Critical limb ischemia

Critical limb ischemia (CLI) is the most serious stage of lower limb arterial disease, often presenting as severe ischemic resting pain, ulcer or tissue gangrene. The treatments for CLI pose a medical challenge. Despite the various treatments available for CLI, there is still no treatment that is entirely effective and acceptable to all patients. Patients with CLI are often elderly and have complex medical conditions, multiple comorbidities, and limited surgical tolerance. Among CLIs, patients with Transatlantic Inter-Society Consensus (TASC) grade D typically exhibit long-segmental and diffuse vascular lesions in their lower extremity arteries, often accompanied by microvascular lesions. It is obviously difficult to reopen multiple extensive segmental vessels with open bypass surgery or endovascular treatment within the limited surgical time, and such methods are ineffective in improving microcirculation. As emerging techniques for lower limb microcirculation reconstruction, tibial cortex transverse distraction and periosteal distraction are both forms of distraction histogenesis (DH) technology, their efficacy in treating CLI is verified, yet their associated treatment parameters still have potential for optimization. Existing biomechanical researches suggest that dynamic stretching may yield superior biological outcomes compared to static stretching, we hypothesize that employing dynamic stretching in tissue distraction techniques may yield a better therapeutic effect, thereby enhancing the efficacy of DH techniques for CLI and reducing the associated complications.

High resolution computed tomography in systemic sclerosis: From diagnosis to follow-up.

Early diagnosis of interstitial lung disease (ILD) and pulmonary hypertension (PH) is crucial in systemic sclerosis (SSc) for both management and treatment. However, diagnosing SSc-ILD can be challenging because symptoms of lung involvement are often non-specific at the early stages of disease. High-resolution computed tomography (HRCT) of the chest is recognized as the most accurate imaging modality for baseline and follow-up evaluation of SSc-ILD. Key features of SSc-ILD on HRCT include a non-specific interstitial pneumonia (NSIP) pattern, with peripheral ground-glass opacities and extensive traction bronchiectasis. Less common HRCT manifestations include usual interstitial pneumonia (UIP) pattern, followed by diffuse alveolar damage (DAD), diffuse alveolar hemorrhage (DAH) and organizing pneumonia (OP). The extent of disease on HRCT is known to relate with prognosis and serial assessments can be helpful in monitoring disease progression or treatment response. We discuss the main chest computed tomography (CT) manifestations of SSc, highlighting the role of imaging at both baseline and follow-up evaluations.

Diffuse white matter pathology in multiple sclerosis during treatment with dimethyl fumarate-An observational study of changes in normal-appearing white matter using proton magnetic resonance spectroscopy.

Multiple sclerosis (MS) is an inflammatory demyelinating disease with neurodegenerative features causing risk for neurologic irreversible disability over time. Examination of normal-appearing white matter (NAWM) changes in MS by proton magnetic resonance spectroscopy (1H-MRS), may detect diffuse white matter pathology that is associated with neurodegeneration. In this observational study of in total twenty-six patients with MS, starting treatment with dimethyl fumarate (DMF), we measured the absolute concentration of metabolites in periventricular NAWM using 1H-MRS at baseline and after one and three years of treatment. Metabolite concentrations were analyzed both cross-sectionally, in relation to 10 controls and longitudinally in relation to disease activity. Patients with MS had higher concentrations of myo-inositol (mIns) in NAWM at baseline compared with controls (mean 5.98 ± 1.37 (SD) and 4.32 ± 1.16 (SD), p<0.01, independent samples t-test). The disease duration was inversely correlated with concentrations of total N-acetylaspartate and N-acetylaspartylglutamate (tNA) (r = -0.62, p<0.01) in NAWM as well as positively to the ratio of mIns and tNA (r = 0.51, p = 0.03). Metabolite concentrations during one-year (n = 19) and three-years (n = 11) follow-up were generally stable. The dropouts were caused by treatment switch after one year, mainly due to new MRI activity. Cross-sectional analyses showed that there was an inverse correlation between concentrations of tNA and mIns at both baseline and at 1 and 3-years follow-up (r = -0.44 to -0.65, p = 0.04 to 0.004). Metabolite concentrations were stable during 1-year follow-up independently of disease activity. Higher concentrations of the astrogliosis marker mIns in MS compared to controls, the inverse relation between MS disease duration and the neuroaxonal integrity marker tNA, as well as the consistent inverse relation between these two metabolites during follow-up, showed that non-lesional white matter pathology is present in this cohort of MS patients in early disease stages. However, metabolite concentrations during follow-up were generally stable and did not reflect differences in disease activity among patients.

Cytokine production in an ex vivo model of SARS-CoV-2 lung infection

IntroductionThe mechanisms of the SARS-CoV-2-triggered complex alterations in immune cell activation and production of cytokines in lung tissue remain poorly understood, in part because of the limited use of adequate tissue models that simulate the structure and cell composition of the lung in vivo. We developed a novel ex vivo model of SARS-CoV-2 infection of lung explants, that maintains the intact tissue composition and the viral load for up to 7–10 days. Using this model, we studied cytokine production during SARS-CoV-2 infection.Materials and methodsLung tissue was monitored for viability and cell composition using flow cytometry and histological analysis. SARS-CoV-2 infection was verified immunohistochemically, viral loads in tissue and culture medium were monitored by qPCR. A panel of 41 cytokines was measured in culture medium using xMAP technology.ResultsThe explant lung tissue was viable and maintained viral infection that influenced the cytokine production. Elevated concentrations of G-CSF, GM-CSF, GRO-a, IFN-g, IL-6, IL-8, IP-10, MCP-3, MIP-1a, PDGF-AA, and VEGF, and decreased IL-1RA concentration were observed in infected tissue compared to non-infected tissue.DiscussionOur results generally reflect the data obtained in COVID-19 patients. GRO-a, IFN-g, IL-6, IL-8, MCP-1, MCP-3, and RANTES correlated with the viral load, forming a distinct pro-inflammatory cluster. Thus, our lung ex vivo model faithfully reproduces some aspects of cytokine alterations in COVID-19 patients at an early disease stage, making the investigation of SARS-CoV-2 infection mechanisms more accessible and providing a potential platform for antiviral drug testing.

The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

A Novel Approach for Chronic Kidney Disease Identification Empowered with Fuzzy Logic

Chronic kidney disease (CKD) is a non-communicable condition that often leads to renal failure, which is when the kidneys are no longer able to filter waste and excess fluid from the body's circulation. Early detection of CKD can slow the progression of the illness and reduce the overall cost of treatment. In this work, a novel approach for identifying CKD using a fuzzy logic system is proposed. The fuzzy system includes eight input parameters such as weight, age, serum creatinine, diastolic blood pressure, systolic blood pressure, glomerular filtration rate, blood glucose, and smoking. The output variable describes a specific patient’s stage of chronic renal disease based on these input factors. The output will indicate the current stage of a patient’s kidney disease. This system can therefore assist specialists in determining the stage of chronic renal disease. The MATLAB software is used to create the fuzzy system. The proposed system is tested on a real data set of patients and the results obtained are promising.

Self-care towards the end of life: A systematic review and narrative synthesis on access, quality and cost.

Policy and practice encourages patients to engage in self-care, with individual patient management and remote monitoring of disease. Much is known of the moderate stage of chronic disease, without a clear understanding of how self-care applies towards the end of life. To review the current evidence on practices of self-care in life-limiting conditions and its impacts on healthcare utilisation, quality of life and associated costs. We systematically searched 10 scientific databases (MEDLINE, CINAHL, Embase, PsycINFO, Cochrane Central, Cochrane Database of Systematic Reviews, Scopus, Sociological Abstracts, Social Work Abstracts and Health Management Information Consortium) from inception to October 2023 with citation and hand searching. A narrative synthesis was undertaken, with quality and relevance assessed using Gough's Weight of Evidence framework. Titles and abstracts were independently screened by three researchers. Findings from 33 studies revealed self-care as increasingly burdensome or unfeasible towards the end of life, with patients delaying use of professional care. Self-care became increasingly burdensome for patients, carers and professionals as illness progressed. Self-monitoring may exacerbate hospitalisations as patients delayed seeking professional help until crises arose. Findings regarding quality were inconclusive, with some evidence suggesting that self-care can decrease care costs. This review has shown that research on self-care is an evolving area of study, with a current focus on acute care and hospitalisations. Future research should seek to provide a more complete account of the relation between self-care and non-acute care use, and quality, with further efforts to study self-care costs incurred through self-funding.

Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma.

Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging.

The incidence and prevalence of Dupuytren’s disease in primary care: results from a text mining approach on registration data

Background The focus of research and management of Dupuytren’s disease (DD) is shifting from relieving symptoms in the later stages of disease towards the prevention of contractures. Treatment services might likewise shift towards primary care. Studying characteristics of DD patients who seek medical care for the first time, may identify a symptomatic target group for early DD treatments. We present the first study that estimates the incidence and prevalence of DD in primary care by applying a text-mining algorithm to registration data. Methods This is a population-based cohort study using electronic health records from Dutch general practices involved in a regional research network. Descriptive statistics were used to describe sex, age, comorbidities and lifestyle factors, the latter two were identified via International Classification of Primary Care (ICPC) codes. Incidence rate was calculated as number of patients with a first contact for DD/1000 person years for the years 2017–2021, point prevalence as the percentage of patients with a contact for DD in 2021. DD contacts were identified using a text-mining algorithm. Results The incidence ranged between 1.41 and 1.72/1000 person years and the overall prevalence was 1.99%. Incidence and prevalence are higher among males and increase with age, peaking between 61 and 80 years. Conclusions Our results of prevalence and incidence of DD in primary care give an insight into the relevant population of patients with symptomatic DD that might be the future target group for potential disease controlling treatments.

Optimising hypoxia PET imaging and its applications in guiding targeted radiation therapy for non-small cell lung cancer: a scoping review.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. Definitive treatment includes chemotherapy and radiation therapy. Tumour hypoxia impacts the efficacy of these treatment modalities. Novel positron-emission tomography (PET) imaging has been developed to non-invasively quantify hypoxic tumour subregions, and to guide personalised treatment strategies. This review evaluates the reliability of hypoxia imaging in NSCLC in relation to various tracers, its correlations to treatment-related outcomes, and to assess if this imaging modality can be meaningfully applied into radiation therapy workflows. A literature search was conducted on the Medline (Ovid) and Embase databases. Searches included terms related to 'hypoxia', 'positron-emission tomography', 'magnetic resonance imaging' and 'lung cancer'. Results were filtered to exclude studies prior to 2011, and animal studies were excluded. Only studies referring to a confirmed pathology of NSCLC were included, while disease staging was not a limiting factor. Full-text English language and translated literature examined included clinical trials, clinical cohort studies and feasibility studies. Quantification of hypoxic volumes in a pre-treatment setting is of prognostic value, and indicative of treatment response. Dosimetric comparisons have highlighted potential to significantly dose escalate to hypoxic volumes without risk of additional toxicity. However, clinical data to support these strategies are lacking. Heterogenous study design and non-standardised imaging parameters have led to a lack of clarity regarding the application of hypoxia PET imaging in NSCLC. PET imaging using nitroimidazole tracers is the most investigated method of non-invasively measuring tumour hypoxia and has potential to guide hypoxia-targeted radiation therapy. Further clinical research is required to elucidate the benefits versus risks of dose-escalation strategies.