Pathophysiology, Diagnosis and Treatment of Bone Diseases

Cirrhosis progresses through distinct stages, with increasing severity and susceptibility to infections due to cirrhosis-associated immune dysfunction. Lymphocyte-based functional assays are considered the gold standard for assessing immune function, although none have been evaluated across different cirrhosis stages. We conducted a pilot study to assess whether performing interferon-γ (IFN-γ) release assays (IGRA), in response to a nonantigenic mitogen (phytohemagglutinin [PHA]), could help classify immune function and disease severity in 70 patients with cirrhosis awaiting liver transplantation. Disease severity ranged from chronic cirrhosis to acute-on-chronic liver failure. We measured IFN-γ release in response to PHA using a fresh heparinized whole-blood protocol. Progressive reduction in IFN-γ release correlated with increased disease severity parameters (with respect to total bilirubin level and number of organ failure instances). A moderate but highly significant correlation was observed between IFN-γ release and CD8+ T lymphocyte count (r=0.52, P <0.001). As a non-antigen-dependent mitogen, PHA enables the global assessment of lymphocyte IFN-γ-releasing capacity. Our whole-blood results suggest that PHA-IGRA testing may provide a useful parameter for characterizing immune dysfunction in patients with cirrhosis. These findings require further validation in larger cohorts to better define the clinical applicability of PHA-IGRA testing.

The primary treatment for active Cushing’s Syndrome (CS) is the surgical removal of the causative tumor. Alternative therapeutic strategies, particularly pharmaceutical approaches, are required when surgery is not feasible, unsuccessful, or in cases of recurrence. Osilodrostat, an adrenal steroidogenesis inhibitor, is approved in Europe and USA for adult patients with CS. The recommended strategy involves gradual titration to achieve eucortisolism, but this approach has limitations. Delayed disease control can be harmful in severe cases, and frequent clinical and laboratory monitoring may be challenging for some patients or during global health crises. To address these challenges, experts have introduced the block-and-replace (B&R) strategy which they consider suitable for selected patients. Due to limited guidance on patient selection and safe implementation, a group of French experts (the authors) who had the opportunity to use osilodrostat outside of clinical trials developed a position statement on B&R. They highlight that osilodrostat B&R strategy is effective and safe, especially when other treatment options are less beneficial. This position paper, while offering a valuable clinical framework, is expert-driven rather than evidence-based, emphasizing the need for further studies, particularly randomized controlled trials, comparing B&R and titration strategies across diverse populations.

Medullary sponge kidney is an entity characterized by pre-calyceal dilatation of the renal tubules, whose pathophysiology is unknown. Tubular anomalies have been described, suggesting impaired medullary function. To better characterize these patients, tools for assessing medullary function and structure are needed. The latter can be evaluated with functional magnetic resonance imaging (fMRI), using blood-oxygen-level-dependent imaging, which quantifies tissue oxygenation, and diffusion-weighted-imaging and T1-mapping sequences which allow fibrosis assessment. The aim of this study was to deeply phenotype medullary sponge kidney patients. We carried out fMRI, measured glomerular filtration rate (mGFR) by iohexol clearance, and metabolic assessment of urolithiasis in patients withmedullary sponge kidney and in healthy controls. The primary endpoint was the comparison of R2*, inversely proportional to oxygen content, measured by blood-oxygen-level-dependent MRI. Secondary endpoints included comparison of T1 and apparent diffusion coefficient, comparison of GFR between medullary sponge kidney patients and controls, and the correlations between fMRI, GFR and biological abnormalities in medullary sponge kidney. Twenty patients withmedullary sponge kidney were included, as well as 13 controls. We observed a higher R2* cortex-to-medulla ratio in medullary sponge kidney patients compared to controls (0.60 vs. 0.55; p = 0.04). No difference was observed for T1 and apparent diffusion coefficient cortex-to-medulla ratio. mGFR was significantly lower in medullary sponge kidney patients (90ml/min/1.73m2 vs 78ml/min/1.73m2; p = 0.008) although estimated GFR did not differ. Medullary cysts were visible on MRI in 60% of medullary sponge kidney patients. We identified impaired renal oxygenation in patients withmedullary sponge kidney. We did not find evidence of kidney fibrosis in medullary sponge kidney. GFR estimation was not accurate in medullary sponge kidney patients. MRI can visualize medullary cystic appearance of medullary sponge kidney.

To facilitate shared decision-making in Chronic obstructive pulmonary disease (COPD), the Assessment of the Burden of COPD (ABC) tool was developed. An integral part of the ABC tool is the ABC scale, a questionnaire to determine COPD burden. The psychometric evidence of the ABC scale is limited. If the data would fit the Rasch model, more accurate scoring would be possible. This would improve the use of the ABC tool. Therefore, the aim of this study is to validate the ABC scale using the Rasch model. We conducted a secondary analysis based on data collected in a pragmatic RCT using Rasch model theory. The ordering of thresholds, reliability and targeting were analysed, and we tested unidimensionality, local independence of items (LD), fit of the data with the model and measurement invariance between groups (DIF). We analysed 551 samples from 176 patients. The analyses confirmed that the ABC scale is a reliable instrument. However, initial analysis showed a poor fit of the data to the Rasch model. After recoding the response options and analysing the fit of the data for the subdomains of the ABC scale, we found ordered thresholds and a good overall model fit. This analysis indicates that the ABC scale assessed three distinct sub-domains: symptoms, physical functioning, and emotional health. We conclude that the ABC scale is a valid instrument to assess COPD burden. While the scale is considered suitable for use in clinical practice and research, we suggest rewording the response options to ensure uniform understanding by respondents. The used data were derived from a previously conducted trial (NTR3788).

Osteolytic metastases located in the vertebrae reduce strength and enhance the risk of vertebral fractures. This risk can be predicted by means of validated finite element models, but their reproducibility needs to be assessed. For that purpose, experimental data are requested. The aim of this study was to conduct open-access experiments on vertebrae, with artificial defect representing lytic metastasis and using well-defined boundary conditions. Twelve lumbar vertebral bodies (L1) were prepared by removing the cortical endplates and creating defects that represent lytic metastases, by drilling the cancellous bone. Vertebral bodies were scanned using clinical High Resolution peripherical Quantitative Computed Tomography before and after defect creation for 3D reconstruction. The specimens were then tested under compression loading until failure. Surface Digital Image Correlation was used to assess strain fields on the anterior wall of the vertebral body. These data (biomechanics data and the tomographic images needed to build subject-specific models) are shared with the scientific community in order to assess different vertebral models on the same dataset.

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.

There has been growing interest in medical research focused on natural products. As a result of the ancestral knowledge passed down through generations and the demands of our current era, there has been an increased demand for new strategies and the search for new molecules with therapeutic potential. This increase is due to new technologies, the evolution of diseases, and the emergence of new ones. In this review, we focus on the work and relevance of Curcumin research, which is one of the main components of Curcuma longa. Additionally, we explore Amaranth in its various reported species and components (seed, leaf, stem) studied. The focus is on the anti-inflammatory therapeutic potential, not only in one, but in different diseases characterized by inflammation and bone destruction. We aim to analyze the possible molecular mechanisms by which curcumin and amaranth act as well as data currently obtained from different studies. This review aims to open a new perspective to the investigation of these compounds in the field of diseases characterized by inflammation and bone destruction. Keywords: curcumin, amaranth, treatment, inflammation, bone.