Transitional and spectrum-based care for idiopathic scoliosis.

OBJECTIVE: The goal of this study is to discuss the transitional nature of idiopathic scoliosis and the variation in treatment and management across the spectrum of age presentation. METHODS: This is a review article that discusses the evaluation, management, and classification of idiopathic scoliosis. The authors searched PubMed/MEDLINE, Google Scholar, and the Cochrane database for articles published up to April 2024. Keywords and MeSH terms relevant to the topic were used, including adolescent idiopathic scoliosis (AIS), adult idiopathic scoliosis (AdIS), adult degenerative scoliosis, young adult idiopathic scoliosis, early-onset scoliosis (EOS), classification, management, follow-up, outcomes, natural history, Cobb angle, and transitional care. Reference lists of selected articles were also searched to identify further articles. Inclusion criteria included English language articles that summarized any type of study design, including randomized controlled trials, observational studies, case-control/series, or metaanalysis, with study populations ranging from infants to > 50-year-old patients. Inter-reviewer disagreement on inclusion of particular articles was resolved through discussion. Related information was analyzed, and relevant concepts related to the transitional period dilemma have been discussed. RESULTS: Each idiopathic scoliosis case needs independent assessment with regard to the age, degree of the curve, and patient-specific presentation. An accurate prediction of the curve progression by considering the patient's remaining growth potential is paramount to the treatment strategy. The classification system for EOS, AIS Lenke classification, AdIS classification, and the Scoliosis Research Society-Schwab classification are important for reliable communication between surgeons treating deformities. Untreated progressive idiopathic scoliosis warrants multidisciplinary management during the transition from EOS stage to AIS and then to AdIS. Also, surgical treatment of untreated AIS transitioning to AdIS is specific and nuanced. AdIS needs to be differentiated from adult degenerative scoliosis because the latter is associated with multiple comorbidities and anatomical differences. CONCLUSIONS: Idiopathic scoliosis presents across the age spectrum with specific age-related decisions that transition into adulthood. Integrated models of both surgical and nonsurgical treatment of idiopathic scoliosis are warranted.

An interdisciplinary integrated specialized one-stop outpatient clinic for idiopathic intracranial hypertension - a comprehensive assessment of patient satisfaction.

BACKGROUND: Management of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop concept. Here, we aimed to evaluate effects of this one-stop concept on subjective patient satisfaction and economic outcome in patients with IIH. METHODS: In a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding subjective patient satisfaction (assessed by the Vienna Patient Inventory). Multivariable binary linear regression models were used to adjust for confounders. RESULTS: Baseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, management within IC concept was associated with statistically significantly higher subjective patient satisfaction (beta = 0.93; p < 0.001) with the strongest effects observed in satisfaction with treatment accessibility and availability (beta = 2.05; p < 0.001). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of IC in these groups. CONCLUSIONS: Interdisciplinary integrated management of IIH statistically significantly and clinically meaningfully improves patient satisfaction - particularly in socioeconomically underprivileged patient groups. Providing structured central coordination to facilitate and improve access to interdisciplinary management provides means to further improve outcome.

Clinico-sero-pathological profiles and risk prediction model of idiopathic inflammatory myopathy (IIM) patients with different perifascicular changes.

AIMS: To explore the clinico-sero-pathological characteristics and risk prediction model of idiopathic inflammatory myopathy (IIM) patients with different muscular perifascicular (PF) changes. METHODS: IIM patients in our center were enrolled and the clinico-sero-pathological data were retrospectively analyzed. A decision tree model was established through machine learning. RESULTS: There were 231 IIM patients enrolled, including 53 with perifascicular atrophy (PFA), 39 with perifascicular necrosis (PFN), and 26 with isolated perifascicular enhancement of MHC-I/MHC-II (PF-MHCn). Clinically, PFA patients exhibited skin rashes and dermatomyositis-specific antibodies (DM-MSAs, 74.5%) except for anti-Mi2. PFN patients showed the most severe muscle weakness, highest creatine kinase (CK), anti-Mi2 (56.8%), and anti-Jo-1 (24.3%) antibodies. PF-MHCn patients demonstrated negative MSAs (48.0%) and elevated CK. Histopathologically, MAC predominantly deposited on PF capillaries in PFA but on non-necrotic myofiber in PFN (43.4% and 36.8%, p < 0.001). MxA expression was least in PF-MHCn (36.0% vs. 83.0% vs. 63.2%, p < 0.001). The decision tree model could effectively predict different subgroups, especially PFA and PFN. CONCLUSIONS: Three types of PF change of IIMs representing distinct clinico-serological characteristics and pathomechanism. Undiscovered MSAs should be explored especially in PF-MHCn patients. The three pathological features could be accurately predicted through the decision tree model.

Bilateral Spondylolysis of Lumbar Vertebra Secondary to Long Spinal Fusion for Idiopathic Scoliosis: A Case Report and Review of Literature.

BACKGROUND: Lumbar spondylolysis is a common cause of low back pain in adolescents. A lot of adolescent idiopathic scoliosis with concomitant spondylolysis has been reported before, but only two cases with acquired spondylolysis following long fusion for scoliosis were reported. We described another similar rare case and discussed its causes and treatment options in this paper. CASE PRESENTATION: A 17-year-old female underwent growing rod implantation, growing rod extension, and final long spinal fusion for idiopathic scoliosis. Then, she suffered from low back pain with a VAS of 1-2 points and gradually aggravated to a VAS of 7-8 points at 3.5 years after the final fusion. The X-ray images showed that there was L4-S1 instability. And the CT scan images showed new bilateral spondylolysis of L5. CONCLUSIONS: These findings suggested that distal mechanical stress might cause spondylolysis of the distal vertebra following long fusion for scoliosis. Surgeons should keep instrumentation as short as possible and avoid choosing a low lumbar as LIV when they decide on the fusion levels.

Idiopathic intracranial hypertension pathogenesis: The jugular hypothesis.

In spite of expanding research, idiopathic intracranial hypertension (IIH) and its spectrum conditions remain challenging to treat. The failure to develop effective treatment strategies is largely due to poor agreement on a coherent disease pathogenesis model. Herein we provide a hypothesis of a unifying model centered around the internal jugular veins (IJV) to explain the development of IIH, which contends the following: (1) the IJV are prone to both physiological and pathological compression throughout their course, including compression near C1 and the styloid process, dynamic muscular/carotid compression from C3 to C6, and lymphatic compression; (2) severe dynamic IJV stenosis with developments of large cervical gradients is common in IIH-spectrum patients and significantly impacts intracranial venous and cerebrospinal fluid (CSF) pressures; (3) pre-existing IJV stenosis may be exacerbated by infectious/inflammatory etiologies that induce retromandibular cervical lymphatic hypertrophy; (4) extra-jugular venous collaterals dilate with chronic use but are insufficient resulting in impaired aggregate cerebral venous outflow; (5) poor IJV outflow initiates, or in conjunction with other factors, contributes to intracranial venous hypertension and congestion leading to higher CSF pressures and intracranial pressure (ICP); (6) glymphatic congestion occurs but is insufficient to compensate and this pathway becomes overwhelmed; and (7) elevated intracranial CSF pressures triggers extramural venous sinus stenosis in susceptible individuals that amplifies ICP elevation producing severe clinical manifestations. Future studies must focus on establishing norms for dynamic cerebral venous outflow and IJV physiology in the absence of disease so that we may better understand and define the diseased state.

Diffuse alveolar hemorrhage in pediatrics: Etiologies and outcomes.

BACKGROUND: Many conditions, including autoimmune disease and idiopathic pulmonary hemosiderosis (IPH), can cause diffuse alveolar hemorrhage (DAH). Little is known about the epidemiology and outcomes in children. OBJECTIVES: This retrospective cohort study sought to describe the etiologies and outcomes of DAH in pediatric patients at a tertiary care center. METHODS: This study involved review of patient records with diagnostic codes or bronchoscopy reports suggestive of pulmonary hemorrhage at a large children's hospital over 11 years (2010-2020). Patients were included if they met criteria for DAH, defined as bilateral pulmonary infiltrates and at least one of the following: (1) hemoptysis, (2) blood visible on bronchoscopic exam without apparent airway source, or (3) DAH noted on biopsy or autopsy. Infants less than 10 days corrected gestational age were excluded. RESULTS: Seventy-one children with DAH were included in the analysis. Cardiovascular disease was the most common etiology. Bleeding diathesis was common, but all patients had other causes of DAH. Patients with IPH were younger than those with autoimmune disease (p < .001). Most (77%) patients required mechanical ventilation, though this was less common among patients with autoimmune disease. Overall mortality was high (37%) but varied based on underlying etiology; mortality was higher in patients with cardiovascular disease (65%) while no deaths were seen in patients with autoimmune disease or IPH (p = .002). Survivors of DAH who performed pulmonary function tests had normal lung function. CONCLUSIONS: DAH frequently causes respiratory failure in children. In our cohort, mortality was highest in patients with cardiovascular disease.

Idiopathic Intracranial Hypertension as a Differential Diagnosis in Persistent Idiopathic Facial Pain: A Case Report.

Persistent idiopathic facial pain (PIFP), previously known as atypical facial pain (ATFP), is a chronic pain disorder with the characteristic of persistent, undulating pain in the face or the teeth without a known cause or any structural correlation. Women are more commonly affected than men. We report a case of a 38-year-old married female patient with a history of Crohn's disease who presented to the oral and maxillofacial surgery (OMFS) clinic with chronic dull bilateral facial pain and headache mainly affecting the right side of the face and neck without a known cause. She was initially diagnosed with PIFP due to a badly decayed right wisdom tooth. Wisdom teeth were extracted secondary to vague complaints of discomfort due to wisdom teeth; however, no significant improvement was noticed. Further investigations were carried out with new CT scans and magnetic resonance venography (MRV), which revealed evidence of having idiopathic intracranial hypertension (IIH), described as increased intracranial pressure with facial pain, headache, tinnitus, and papilledema. The patient was referred to neurology and received appropriate treatment. She began her treatment with topiramate, then transitioned to acetazolamide, underwent bilateral botulinum toxin (botox) injections into the temporal region, and underwent regular follow-up. The patient was significantly improved. Idiopathic intracranial hypertension must be ruled out in cases of PIFP that do not respond to ordinary treatment measures.

Down-regulation of CYTL1 attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting M2 macrophage polarization via the TGF-ß/CCN2 axis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic inflammation, lung tissue fibrotic changes and impaired lung function. Pulmonary fibrosis 's pathological process is thought to be influenced by macrophage-associated phenotypes. IPF treatment requires specific targets that target macrophage polarization. Cytokine-like 1(CYTL1) is a secreted protein with multiple biological functions first discovered in CD34+ haematopoietic cells. However, its possible effects on IPF progression remain unclear. This study investigated the role of CYTL1 in IPF progression in a bleomycin-induced lung injury and fibrosis model. In bleomycin-induced mice, CYTL1 is highly expressed. Moreover, CYTL1 ablation alleviates lung injury and fibrosis in vivo. Further, downregulating CYTL1 reduces macrophage M2 polarization. Mechanically, CYTL1 regulates transforming growth factor ß (TGF-ß)/connective tissue growth factor (CCN2) axis and inhibition of TGF-ß pathway alleviates bleomycin-induced lung injury and fibrosis. In conclusion, highly expressed CYTL1 inhibits macrophage M2 polarization by regulating TGF-ß/CCN2 expression, alleviating bleomycin-induced lung injury and fibrosis. CYTL1 could, therefore, serve as a promising IPF target.

Adiponectin suppresses stiffness-dependent, pro-fibrotic activation of lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible respiratory disease with limited therapeutic options. A hallmark of IPF is excessive fibroblast activation and extracellular matrix (ECM) deposition. The resulting increase in tissue stiffness amplifies fibroblast activation and drives disease progression. Dampening stiffness-dependent activation of fibroblasts could slow disease progression. We performed an unbiased, next generation sequencing (NGS) screen to identify signaling pathways involved in stiffness-dependent lung fibroblast activation. Adipocytokine signaling was downregulated in primary lung fibroblasts (PFs) cultured on stiff matrices. Re-activating adipocytokine signaling with adiponectin suppressed stiffness-dependent activation of human PFs. Adiponectin signaling depended on CDH13 expression and p38 mitogen-activated protein kinase gamma (p38MAPKγ) activation. CDH13 expression and p38MAPKγ activation were strongly reduced in lungs from IPF donors. Our data suggest that adiponectin-signaling via CDH13 and p38MAPKγ activation suppresses pro-fibrotic activation of fibroblasts in the lung. Targeting of the adiponectin signaling cascade may provide therapeutic benefits in IPF.

Exploring vertebral bone density changes in a trunk with adolescent idiopathic scoliosis: a mechanobiological modeling investigation of intact and unilaterally paralyzed muscles.

This study aimed to elucidate the vertebral bone density variations associated with adolescent idiopathic scoliosis (AIS), specifically examining the impact of unilateral muscle paralysis using an integrated approach combining Frost's Mechanostat theory, a three-dimensional subject-specific finite element model and a musculoskeletal model of the L2 vertebra. The findings revealed a spectrum of bone density values ranging from 0.29 to 0.31 g/cm3, along with vertebral micro-strain levels spanning from 300 to 2200, consistent with existing literature. Furthermore, the ratio of maximum von Mises stress between the concave and convex side in the AIS model with intact muscles was approximately 1.08, which decreased by 4% due following unilateral paralysis of longissimus thoracis pars thoracic muscle. Overall, this investigation contributes to a deeper understanding of AIS biomechanics and lays the groundwork for future research endeavors aimed at optimizing clinical management approaches for individuals with this condition.

Decoding pulsatile patterns of cerebrospinal fluid dynamics through enhancing interpretability in machine learning.

Analyses of complex behaviors of Cerebrospinal Fluid (CSF) have become increasingly important in diseases diagnosis. The changes of the phase-contrast magnetic resonance imaging (PC-MRI) signal formed by the velocity of flowing CSF are represented as a set of velocity-encoded images or maps, which can be thought of as signal data in the context of medical imaging, enabling the evaluation of pulsatile patterns throughout a cardiac cycle. However, automatic segmentation of the CSF region in a PC-MRI image is challenging, and implementing an explained ML method using pulsatile data as a feature remains unexplored. This paper presents lightweight machine learning (ML) algorithms to perform CSF lumen segmentation in spinal, utilizing sets of velocity-encoded images or maps as a feature. The Dataset contains 57 PC-MRI slabs by 3T MRI scanner from control and idiopathic scoliosis participants are involved to collect data. The ML models are trained with 2176 time series images. Different cardiac periods image (frame) numbers of PC-MRIs are interpolated in the preprocessing step to align to features of equal size. The fivefold cross-validation procedure is used to estimate the success of the ML models. Additionally, the study focusses on enhancing the interpretability of the highest-accuracy eXtreme gradient boosting (XGB) model by applying the shapley additive explanations (SHAP) technique. The XGB algorithm presented its highest accuracy, with an average fivefold accuracy of 0.99% precision, 0.95% recall, and 0.97% F1 score. We evaluated the significance of each pulsatile feature's contribution to predictions, offering a more profound understanding of the model's behavior in distinguishing CSF lumen pixels with SHAP. Introducing a novel approach in the field, develop ML models offer comprehension into feature extraction and selection from PC-MRI pulsatile data. Moreover, the explained ML model offers novel and valuable insights to domain experts, contributing to an enhanced scholarly understanding of CSF dynamics.

Awareness level of idiopathic normal pressure hydrocephalus among health-care providers.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that primarily affects the geriatric population. It was first introduced by Adams et al. in 1965. A gradual decline in cognitive function, urinary incontinence, and gait disturbances characterizes the disease. This condition is believed to be underdiagnosed, and awareness of such pathology is vital, as the treatment is very effective and can reverse the symptoms. Methods: This questionnaire-based cross-sectional study aimed to assess awareness levels regarding iNPH among non-neuroscience healthcare providers in Saudi Arabia. Results: A total of 269 healthcare providers participated in this study, with data collected through an online questionnaire. About 80.6% of the participants had heard of the disease, while 56.5% were aware of the disease symptomology. About 50% of physicians did not encounter iNPH patients in clinical practice. Previous clinical exposure to iNPH patients correlates significantly with an awareness of disease symptoms, investigation, treatment modalities, and outcome. Clinical experience positively impacts physicians' awareness as it correlates with a better understanding of diagnostic methods and disease outcomes. Conclusion: The study highlights the need for targeted educational interventions, especially among family physicians and general practitioners with no previous experience with iNPH patients, as well as interdisciplinary collaboration to address gaps in awareness and enhance early diagnosis of iNPH patients.

Intra-articular corticosteroid utilization and characterizations of use in juvenile idiopathic arthritis within the PR-COIN registry.

Objective: Intra-articular corticosteroid injections (IACI) have been shown to be effective at improving arthritis across juvenile idiopathic arthritis (JIA) categories. The American College of Rheumatology (ACR) recommends IACI use as primary and adjunctive therapy for JIA patients. However, there remains minimal data describing actual IACI use in North America. The objective of this study was to describe and to evaluate IACI use in JIA, utilizing the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry. Methods: Study participants from 13 sites were enrolled in the PR-COIN registry from 2011 to 2015. Demographic and clinical variables were summarized and Chi-squared and t-tests were used to evaluate differences between participants who did or did not receive IACI. Multiple logistic regression models were used to evaluate characteristics associated with IACI treatment. Results: Our study included 3,241 participants, the majority of whom were white (85%), female (71%) and had oligoarticular JIA (39%). IACI was administered at least once in 23% of participants, the majority of whom had oligoarticular disease (52.5%), but overall use in oligoarticular participants was low at 30.8%. IACI use varied significantly between treatment centers and use was associated with oligoarticular disease, ANA positivity, and use of other systemic medications. Conclusion: This study demonstrates that participants with JIA enrolled in the PR-COIN registry between 2011 and 2015 with persistent oligoarticular disease, ANA positivity, and use of other systemic medications were more likely to receive IACI. However, IACI use was lower than expected for oligoarticular participants.

Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is classified under fibrotic interstitial pneumonia, characterized by a chronic and progressive course. The predominant clinical features of IPF include dyspnea and pulmonary dysfunction. AIM: To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients. METHODS: A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023. These patients were divided into two groups: control group (n = 53) and observation group (n = 60). In the control group, patients received routine therapy in combination with methylprednisolone tablets, while those in the observation group received routine therapy together with pirfenidone. After applying these distinct treatment approaches to the two groups, we assessed several parameters, including the overall effectiveness of clinical therapy, the occurrence of adverse reactions (e.g., nausea, vomiting, and anorexia), symptom severity scores, pulmonary function index levels, inflammatory marker levels, and the 6-min walk distance before and after treatment in both groups. RESULTS: The observation group exhibited significantly higher rates than the control group after therapy, with a clear distinction (P < 0.05). After treatment, the observation group experienced significantly fewer adverse reactions than the control group, with a noticeable difference (P < 0.05). When analyzing the symptom severity scores between the two groups of patients after treatment, the observation group had significantly lower scores than the control group, with a distinct difference (P < 0.05). When comparing the pulmonary function index levels between the two groups of patients after therapy, the observation group displayed significantly higher levels than the control group, with a noticeable difference (P < 0.05). Evaluating the inflammatory marker data (C-reactive protein, interleukin-2 [IL-2], and IL-8) between the two groups of patients after therapy, the observation group exhibited significantly lower levels than the control group, with significant disparities (P < 0.05). Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group, with a marked difference (P < 0.05). CONCLUSION: Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function, elevate inflammatory factor levels, and increase the distance covered in the 6-min walk test. This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Unusual spontaneous intraperitoneal hemorrhage: three case reports.

Introduction and importance: Spontaneous hemoperitoneum (SH) is a rare, life-threatening condition characterized by nontraumatic and non-iatrogenic intraperitoneal bleeding. This article explores three unique cases of SH, shedding light on unusual causes and emphasizing the critical role of diagnostic imaging and exploratory laparotomy in management. METHODS: The study was a retrospective single-center non-consecutive case series. RESULTS: We report three distinct cases of SH, each originating from uncommon sources: rupture of greater omentum arterio-venous malformation, a branch of the left gastric artery, and pathological splenic rupture. Clinical evaluation, diagnostic imaging, and surgical interventions are detailed for each case. CONCLUSION: These rare cases underscore the diverse etiologies of SH, including idiopathic omental bleeding, gastric intramural hematoma, and atraumatic splenic rupture. Enhanced CT imaging plays a crucial role in diagnosis, enabling the characterization of underlying pathologies. Exploratory laparotomy proves to be an essential treatment option for unstable patients with suspected or confirmed diagnoses of SH.

Nintedanib and miR-29b co-loaded lipoplexes in idiopathic pulmonary fibrosis: formulation, characterization, and in vitro evaluation.

OBJECTIVE: This study was aimed to develop a cationic lipoplex formulation loaded with Nintedanib and miR-29b (LP-NIN-miR) as an alternative approach in the combination therapy of idiopathic pulmonary dibrosis (IPF) by proving its additive anti-fibrotic therapeutic effects through in vitro lung fibrosis model. SIGNIFICANCE: This is the first research article reported that the LP-NIN-MIR formulations in the treatment of IPF. METHODS: To optimize cationic liposomes (LPs), quality by design (QbD) approach was carried out. Optimized blank LP formulation was prepared with DOTAP, CHOL, DOPE, and DSPE-mPEG 2000 at the molar ratio of 10:10:1:1. Nintedanib loaded LP (LPs-NIN) were produced by microfluidization method and were incubated with miR-29b at room temperature for 30 min to obtain LP-NIN-miR. To evaluate the cellular uptake of LP-NIN-miR, NIH/3T3 cells were treated with 20 ng.mL-1 transforming growth factor-ß1 (TGF-ß1) for 96 h to establish the in vitro IPF model and incubated with LP-NIN-miR for 48 h. RESULTS: The hydrodynamic diameter, polydispersity index (PDI), and zeta potential of the LP-NIN-miR were 87.3 ± 0.9 nm, 0.184 ± 0.003, and +24 ± 1 mV, respectively. The encapsulation efficiencies of Nintedanib and miR-29b were 99.8% ± 0.08% and 99.7% ± 1.2%, respectively. The results of the cytotoxicity study conducted with NIH/3T3 cells indicated that LP-NIN-miR is a safe delivery system. CONCLUSIONS: The outcome of the transfection study proved the additive anti-fibrotic therapeutic effect of LP-NIN-miR and suggested that lipoplexes are effective delivery systems for drug and nucleic acid to the NIH/3T3 cells in the treatment of IPF.

[Idiopathic membranous nephropathy with focal segmental sclerosis].

AIM: To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. MATERIALS AND METHODS: 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. RESULTS: At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; р=0.039) were associated with the CKD progression. CONCLUSION: In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

Prognostic model of fibroblasts in idiopathic pulmonary fibrosis by combined bulk and single-cell RNA-sequencing.

Background: Fibroblasts play an important role in the development of idiopathic pulmonary fibrosis (IPF). Methods: We employed single-cell RNA-sequencing data obtained from the Gene Expression Omnibus database to perform cell clustering and annotation analyses. We then performed secondary clustering of fibroblasts and conducted functional enrichment and cell trajectory analyses of the two newly defined fibroblast subtypes. Bulk RNA-sequencing data were used to perform consensus clustering and weighted gene co-expression network analysis. We constructed a fibroblast-related prognostic model using least absolute shrinkage, selection operator regression, and Cox regression analysis. The prognostic model was validated using a validation dataset. Immune infiltration and functional enrichment analyses were conducted for patients in the high- and low-risk IPF groups. Results: We characterized two fibroblast subtypes that are active in IPF (F3+ and ROBO2+). Using fibroblast-related genes, we identified five genes (CXCL14, TM4SF1, CYTL1, SOD3, and MMP10) for the prognostic model. The area under the curve values of our prognostic model were 0.852, 0.859, and 0.844 at one, two, and three years in the training set, and 0.837, 0.758, and 0.821 at one, two, and three years in the validation set, respectively. Conclusion: This study annotates and characterizes different subtypes of fibroblasts in IPF.

Causal association of juvenile idiopathic arthritis or JIA-associated uveitis and gut microbiota: a bidirectional two-sample Mendelian randomisation study.

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (ß: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.

Efficacy of sulodexide in treating idiopathic membranous nephropathy among Chinese patients: a meta-analysis.

OBJECTIVE: To evaluate the efficacy of Sulodexide in treating idiopathic membranous nephropathy (IMN) in the Chinese population. METHODS: We systematically reviewed all eligible randomized clinical trials (RCTs) conducted in China that investigated the effects of Sulodexide on IMN. Three RCTs published between 2013 and 2022 were included, encompassing a total of 146 patients. The primary outcomes evaluated were changes in urine total protein (UTP), serum albumin (ALB), cholesterol (CHOL), and fibrinogen (FIB) levels. RESULTS: Statistically significant differences were observed in the Sulodexide treatment group compared to the control group for the following parameters: reduction in UTP and CHOL, increase in ALB, and reduction in FIB levels. CONCLUSION: Sulodexide, when combined with conventional therapy, effectively reduces UTP and CHOL levels, decreases FIB levels, and increases ALB in Chinese patients with IMN.