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Interleukin-6 as a prognostic marker in acute kidney injury and its klotho-dependent regulation.
No full text20.500.12530/87857In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI. Plasma levels of IL-6, klotho and FGF23 were analysed in samples from 28 patients with AKI and related to renal function on hospital admission, and after 24 and 72 h. In addition, the predictive capacity of IL-6 on AKI-associated mortality was analysed at the three study time points. In an experimental nephrotoxic -AKI mouse model, systemic IL-6 and FGF23 values were also analysed 24 and 72 h after induction of kidney damage, as well as in mice overexpressing the anti-ageing protein, klotho. Systemic IL-6 levels increased in AKI patients, especially in hospital admission time, and decreased in parallel with improving renal function. At the same time as IL-6 values increased, there was an increase in FGF23 and a decrease in klotho levels, with a significant and positive correlation between IL-6 and FGF23 levels. In addition, we obtained that systemic IL-6 levels were a good predictor of mortality in these patients, with an area under the curve equal to one at 72 h after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24 h of kidney damage. Nevertheless, in transgenic mice overexpressing klotho, there was no such increase in any of them. There is an association between renal damage and increased levels of IL-6 and FGF23 in patients with AKI, especially on hospital admission time. Moreover, IL-6 levels are able to predict mortality in these patients, being a promising prognostic biomarker at any study time with a strong prediction at 72 h after patient admission. Maintaining adequate klotho levels could prevent the IL-6 mediated inflammatory response and therefore also reduce the degree and severity of renal damage after AKI
An Update on Advances in Hypopituitarism: Etiology, Diagnosis, and Current Management.
No full text20.500.12530/87909This article provides an updated review of hypopituitarism (HP), an endocrine disorder characterized by a deficiency of one or more pituitary hormones. The various etiologies are reviewed, including pituitary neuroendocrine tumors (PitNETs), hypothalamic lesions, genetic mutations, and acquired factors such as head trauma, medications, neoplasms, and infiltrative diseases. It is noted that PitNETs are responsible for approximately half of the cases in adults, whereas in children the causes are predominantly congenital. Diagnosis is based on clinical evaluation and hormonal testing, with identification of the specific hormonal deficiencies essential for effective treatment. Laboratory tests present challenges and limitations that must be understood and addressed. Hormone replacement therapy is the mainstay of treatment, significantly improving patients' quality of life. It is important to know the possible interactions between hormone replacement therapies in HP. Recent advances in understanding the pathophysiology of HP and the importance of a multidisciplinary approach to the management of associated complications are discussed. This article emphasizes the need for comprehensive evaluation and continuous follow-up to optimize outcomes in patients with HP and highlights the importance of ongoing research to improve diagnostic and treatment strategies
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era.
No full text20.500.12530/87913Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC). Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen. The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups. LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications
Damage in a large systemic lupus erythematosus cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER) with emphasis on the cardiovascular system: a longitudinal analysis.
No full text20.500.12530/87913To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort. Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded. During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI. New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE
Sagittal alignment of diverse mechanical complications following adult spinal deformity surgery.
No full textTo compare the sagittal alignment of patients with diverse mechanical complications (MCs) following adult spinal deformity (ASD) surgery with that of patients without MCs. A total of 371 patients who underwent ASD surgery were enrolled. The sagittal spinopelvic parameters were measured preoperatively and at the 6-month and last follow-up, and the global alignment and proportion (GAP) score was calculated. The subjects were divided into non-MC and MCs groups, and the MCs group was further divided into rod fracture (RF), screw breakage (SB), screw dislodgement (SD) and proximal junctional kyphosis (PJK) subgroups. Preoperatively, the RF group had greater thoracolumbar kyphosis (TLK) and relative upper lumbar lordosis (RULL); the SB group had the largest pelvic incidence (PI) and lumbar lordosis (LL); the SD group had the least global sagittal imbalance; and the PJK group had the highest thoracic kyphosis (TK), TLK and RULL. At the last follow-up, the RF and SB groups featured a large PI minus LL (PI-LL), while the PJK group featured a prominent TK; all the MCs subgroups had sagittal malalignment and a higher GAP score, and the SB group had the most severe cases. Logistic regressions showed that the relative spinopelvic alignment (RSA) score was correlated with RF, SB and SD, while the RSA and age scores were associated with PJK. Each patient with MCs had individual characteristics in the sagittal plane following ASD surgery, which may be helpful to understand the pathophysiology of poor sagittal alignment with its subsequent MCs and guide an eventual revision strategy
Accuracy of Smartwatch Electrocardiographic Recording in the Acute Coronary Syndrome Setting: Rationale and Design of the ACS WATCH II Study.
No full text20.500.12530/87908Background: Acute Coronary Syndrome (ACS), with or without ST-segment elevation, is a major contributor to global mortality and morbidity. Swift diagnosis and treatment are vital for mitigating cardiac damage and improving long-term outcomes. The 12-lead electrocardiogram (ECG) currently serves as the gold standard for diagnosis in ACS with ST-segment elevation and may support the diagnosis in ACS without ST-segment elevation. However, the growing prevalence of smartwatches enables the acquisition of electrocardiographic data without traditional ECG equipment. While smaller studies support smartwatch ECG use, larger-scale validation within ACS remains lacking. The ACS WATCH II study aims to validate smartwatch ECG recordings for ACS. Methods: The primary objective is to validate smartwatch-obtained electrocardiographic data in patients presenting with ACS. Two cohorts of 120 patients each, presenting ACS with and without ST-segment elevation, will be assessed. Smartwatches will capture recordings of leads I, III, and V2 alongside standard ECGs. These leads, chosen due to a 97% ACS diagnosis sensitivity in previous studies, will undergo blind evaluation by two experienced external assessors against conventional ECG. Additionally, a control sample of 60 healthy individuals will be included. Conclusions: ACS WATCH II pioneers large-scale prospective validation of smartwatch ECG recordings in ACS patients. Additionally, it indirectly validates a swift diagnostic approach using three leads (I, III, and V2). This could expedite time-critical ACS diagnoses and simplify access through smartwatch-based diagnosis
Autophagy in Its (Proper) Context: Molecular Basis, Biological Relevance, Pharmacological Modulation, and Lifestyle Medicine.
No full text20.500.12530/87887Autophagy plays a critical role in maintaining cellular homeostasis and responding to various stress conditions by the degradation of intracellular components. In this narrative review, we provide a comprehensive overview of autophagy's cellular and molecular basis, biological significance, pharmacological modulation, and its relevance in lifestyle medicine. We delve into the intricate molecular mechanisms that govern autophagy, including macroautophagy, microautophagy and chaperone-mediated autophagy. Moreover, we highlight the biological significance of autophagy in aging, immunity, metabolism, apoptosis, tissue differentiation and systemic diseases, such as neurodegenerative or cardiovascular diseases and cancer. We also discuss the latest advancements in pharmacological modulation of autophagy and their potential implications in clinical settings. Finally, we explore the intimate connection between lifestyle factors and autophagy, emphasizing how nutrition, exercise, sleep patterns and environmental factors can significantly impact the autophagic process. The integration of lifestyle medicine into autophagy research opens new avenues for promoting health and longevity through personalized interventions
Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU.
No full text20.500.12530/87870The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles
Prosthetic Joint Infections Caused by Mycobacterium tuberculosis Complex-An ESGIAI-ESGMYC Multicenter, Retrospective Study and Literature Review.
No full text20.500.12530/87854While tuberculosis remains a significant global health concern, prosthetic joint infections (PJIs) caused by members of the Mycobacterium tuberculosis complex are exceptionally rare. Our objective is to perform a retrospective search of new cases of this disease and analyze all cases available in the literature of tuberculous PJIs, aiming to detect factors that may influence patient outcomes. The ESGIAI and ESGMYC study groups were used to collect information on non-published cases of tuberculous prosthetic joint infections (PJIs). Additionally, a literature review of all published cases of tuberculous PJIs was conducted. All identified cases in the retrospective study and in the literature review were merged and included in the statistical analysis, involving both univariate and multivariate analyses. Fifteen previously unreported cases of tuberculous prosthetic joint infections (PJIs) from four countries were detailed. Among them, ten patients were female, with a median age of 76 years. The hip was affected in 13 cases. Seven patients experienced co-infection with another microorganism. Treatment approaches varied, with 13 patients undergoing implant removal, one treated with DAIR (debridement, antibiotics, and implant retention), and one case was treated with an unknown treatment method. All patients received antibiotic therapy and achieved a cure. The literature review that was conducted detected 155 published cases. Univariate analysis revealed a statistical significance for previous tuberculosis, joint, and no importance of surgery for cure. Tuberculous prosthetic joint infection (PJI) is a rare condition, typically presenting as a localized chronic infection. Antibiotic treatment is essential for the management of these patients, but neither surgical treatment nor duration of treatment seems to have importance in the outcome
Notochordal cell derived lesions: a 55-year casuistic analysis of 50 cases with radiologic-pathologic correlation in a tertiary referral hospital, and literature review.
No full textDistinct lesions are derived from notochordal cells (NCDL), ranging from benign to malignant ones. This study presents fifty NCDL cases diagnosed in a tertiary hospital of reference from the past 55 years: forty-two conventional chordomas, including one chondroid chordoma subtype, four benign notochordal cell tumors (BNCT), two conventional chordomas with BNCT foci, and two dedifferentiated chordomas. All patients were adults. Three BNCT were incidentally diagnosed, and one case presented local pain. Chordomas began with local pain and/or neurological symptoms. BNCT were well-defined intraosseous lesions, hypointense on T1-weighted images (WI) and hyperintense on T2-WI, without enhancement in the contrast. Conventional chordomas, including its chondroid subtype, were lobulated masses with cortical disruption and soft tissue extension, hypointense on T1-WI and hyperintense on T2-WI, with variable contrast enhancement. BNCT were histologically composed of solid sheets of vacuolated cells with clear cytoplasm and round and central nuclei. No atypia, lobular growth pattern, myxoid matrix, or bone infiltration were seen. Conventional chordomas were histologically composed of physaliphorous cells in a myxoid stroma with lobulated and infiltrating growth patterns. Observational follow-up using radiological controls was decided on for the BNCT cases. None of these cases presented local recurrence or metastasis. En-bloc resection and adjuvant radiotherapy were selected for sacral and vertebral chordoma cases. Sixteen patients died due to tumor-related factors; twenty-eight presented local recurrence, and four developed distant metastases. New therapeutic options are being studied for chordoma cases. Clinical, radiological, and histopathological data are necessary to properly diagnose and follow up of NCDL