General Hospital Asklepieio Voulas

Nowadays, adipose tissue is recognized as a dynamic endocrine organ that profoundly affects metabolic, reproductive and skeletal physiology. Apart from its role in energy storage, adipocytes secrete cytokines and bioactive proteins, known as adipokines, that contribute to the regulation of the hypothalamic-pituitary-gonadal axis, gonadal steroidogenesis and bone remodeling. Reciprocal signaling between adipose tissue, bone and the reproductive system forms a complex endocrine network linking energy balance to fertility and bone homeostasis. Key mediators, including leptin, adiponectin, resistin, visfatin and bone marrow adipose tissue, interact with osteoblast-derived proteins, such as osteocalcin, to modulate steroidogenesis and metabolic function. Vitamin D, stored in adipose tissue and acting through its receptor, further integrates these pathways by coordinating calcium metabolism, reproduction and skeletal integrity. This review aims to present mechanistic and clinical evidence demonstrating how metabolic signals derived from adipose depots communicate with gonadal and skeletal tissues through overlapping endocrine, paracrine and autocrine networks. Attention is paid to depot-specific effects, bidirectional feedback between adipose tissue and bone signaling, as well as in emerging implications for infertility, osteoporosis and metabolic bone disease. Finally, we discuss critical knowledge gaps and research priorities, to elucidate novel therapeutic approaches for reproductive and skeletal disorders.

Sepsis is heterogeneous, and the optimal strategy for tailoring immunotherapy is uncertain. To investigate whether precision immunotherapy guided by the presence of macrophage activation-like syndrome or sepsis-induced immunoparalysis improves organ dysfunction by day 9. A randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted in 6 countries. Patients with sepsis, defined by Sepsis-3, were included if they had community-acquired or hospital-acquired pneumonia or ventilator-associated pneumonia or bacteremia and sepsis and had displayed either macrophage activation-like syndrome (blood ferritin >4420 ng/mL) or sepsis-induced immunoparalysis (blood ferritin ≤4420 ng/mL and <5000 human leukocyte antigen DR receptors on CD45/CD14 monocytes). The first patient was enrolled August 5, 2021, and the last follow-up, April 29, 2024. Eligible patients were randomized to receive standard care and precision immunotherapy or standard care and placebo. Those in the precision immunotherapy group with macrophage activation-like syndrome received anakinra intravenously (IV) and placebo subcutaneously, and those with sepsis-induced immunoparalysis received subcutaneous recombinant human interferon gamma and IV placebo. Those in the placebo group received both IV and subcutaneous placebo. Treatment was administered for up to 15 days. The primary end point was a decrease of at least 1.4 points in the mean Sequential Organ Failure Assessment (SOFA) score from baseline by day 9. The SOFA score evaluates 6 organ systems, ranging from 0, no dysfunction, to 4, failure, and the total score ranges from 0, normal, to 24, most severe form of multiorgan failure. Key secondary outcomes included 28-day mortality. Of 672 patients assessed for eligibility, 281 were randomized and 276 were included in the primary analysis population (mean [SD] age, 70 [13] years; 93 females [33.7%]; median baseline SOFA score, 9 [IQR, 7-11]). The SOFA decrease end point was attained by 46 of 131 patients (35.1%) in the precision immunotherapy group and by 26 of 145 patients (17.9%) in the placebo group (difference, 17.2% [95% CI, 6.8% to 27.2%]; P = .002). Mortality at 28 days was not statistically significantly different between groups. A total of 1069 serious treatment-emergent adverse events (88.8%) were reported; increased incidence of anemia was noted in the anakinra group; and hemorrhage in the recombinant human interferon gamma group. Among patients with sepsis, precision immunotherapy targeting macrophage activation-like syndrome and sepsis-induced immunoparalysis improved organ dysfunction by day 9 compared with placebo. ClinicalTrials.gov Identifier: NCT04990232.

Bladder dysfunction is a common clinical problem in stroke patients and a strong prognostic factor of disability and exerts an enormous impact on health and economy. The aim of this narrative review was tο examine the pathophysiological mechanisms of lower urinary tract symptoms after stroke, as well as the relevant clinical anatomy. Normal micturition is achieved through complex coordination between brain regions, spinal cord, and peripheral nerves, and anatomic brain connectivity is crucial to lower urinary tract physiology. The most important neurotransmitters involved in bladder control include γ-aminobutyric acid, opioids, glutamate, dopamine, norepinephrine, acetylcholine, and nitric oxide. The precise correspondence between brain damage and relevant urinary symptoms is not well understood. Urodynamic changes after stroke include detrusor overactivity, dyssynergia, and uninhibited sphincter relaxation. Several brain regions could be implicated in post-stroke urinary dysfunction. Brainstem lesions can cause various urinary symptoms. A lesion superiorly to the pontine micturition center (PMC) results in an uninhibited bladder, whereas a lesion between the sacral spinal cord and PMC leads to either a spastic bladder or sphincter-detrusor dyssynergia. Supra-pontine lesions usually cause bladder storage dysfunction. Frontoparietal lesions have been associated with urinary incontinence and insular lesions with urinary retention. Understanding the mechanisms underlying the dysfunction of the lower urinary tract following stroke can aid in the development of new therapeutic strategies for these patients.

To present the characteristics of patients with potential difficult-to-treat (D2T) PsA. We used data from the Greek multicentre registry of PsA patients. D2T PsA was defined as follows: patients with at least 6 months' disease duration, who have failed to at least one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (P < 0.0001) and were more likely to have higher BMI (P = 0.023) and a history of IBD (P = 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (P = 0.001 and P = 0.008, respectively). Moreover, female gender (P = 0.034) in the MODA analysis and axial disease (P = 0.040) in the MDA analysis were independent variables for D2T PsA. Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial disease and history of IBD were also associated with D2T PsA.

Multiple sclerosis is a systemic autoimmune disease characterized by demyelination of nerves within the central nervous system. The prevalence of the disease is increasing. Cases with varying severity are observed.Multiple sclerosis is accompanied by severe osteoporosis, which may lead to fractures and may compromise patient mobility.The aim was to describe the case of a patient with multiple sclerosis who developed severe osteoporosis with multiple fractures. A female patient was diagnosed with multiple sclerosis at the age of 52. At the age of 63, she presented with a fracture of the right femur.She was treated surgically with total arthroplasty.Osteoporosis was diagnosed and treatment was initiated.Seven months later the patient fell upon the fractured leg and developed a periprosthetic femoral fracture.She was treated with open reduction and internal fixation.Thereafter, bisphosphonates were administered.The patient can now walk with difficulty, independently, without orthotic help.In this case report, we have presented a case of multiple sclerosis who developed severe osteoporosis with multiple fractures.

ObjectiveTo discern predictive factors for the development of incident lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients.MethodsPatients with SLE, according to American College of Rheumatology 1997 criteria and/or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria, from a mixed prevalent and incident cohort (‘Attikon’ Lupus cohort) were followed for development of biopsy-proven nephritis. Demographics, clinical characteristics and laboratory values at baseline were compared against patients who did not develop LN. LN-free survival curves were generated using the Kaplan-Meier method and a multivariate Cox proportional hazards model was used to identify independent predictors of LN, after adjusting for potential confounders.ResultsOf 570 patients, 59 manifested LN as presenting clinical manifestation and 66 developed LN during follow-up (total 21.9% of the entire cohort). On univariate analysis, male sex, younger age at disease onset, low C3 and/or C4 and high anti-dsDNA titre at baseline were associated with a higher risk of LN. On multivariate analysis, baseline factors predictive of future nephritis were male sex (aHR 3.79, 95% CI: 1.61–8.91, p < 0.01), younger age of SLE diagnosis (aHR per year 0.94, 95% CI: 0.91–0.98, p < 0.01), low C3 and/or C4 (aHR 3.64, 95% CI: 1.06–12.5, p < 0.05) and high anti-dsDNA titre (although not statistically significant, a clear trend was evident, aHR 2.45, 95% CI: 0.96–6.25, p = 0.062) (figure 1). Of note, combined serologic activity at baseline conferred the most pronounced risk, underscoring the additive effect of each factor (figure 2).ConclusionsMale sex, younger age and -especially combined- serologic activity at the time of SLE diagnosis are strongly associated with LN development. Vigilant surveillance for early signs of nephritis is particularly warranted in these subsets of patients. P88 Figure 1Adjusted hazard ratios after multivariate analysis of lupus nephritis predictive factors P88 Figure 2Cumulative lupus nephritis incidence according to serologic activity at baseline