Search Results (68)

Background: Postoperative pancreatic fistula remains a frequent complication after distal pancreatectomy and represents the first cause for major morbidity and mortality. Multiple strategies have been proposed to mitigate the severity of pancreatic fistula, but their real benefits remain inconclusive. This study aimed to identify effective mitigation strategies for clinically relevant pancreatic fistula (CR-POPF) through a systematic review of randomized clinical trials. Methods: A systematic search of the Medline and Web of Science databases was conducted for studies published between 2006 and February 2025. Eligible studies included randomized clinical trials evaluating strategies to mitigate clinically relevant postoperative pancreatic fistula following distal pancreatectomy. Only studies in English and involving human subjects were included. Results: Twenty-seven studies were found eligible, comprising 4062 patients, treated with 22 different strategies classified in 8 categories: tissue coverage, sealants and glues, systemic corticoids, analogues of somatostatin, anastomosis of the stump, drain usage, closure of the stump and transpapillary stent. Only 6 studies demonstrated a significant reduction in CR-POPF, strategies applied include systemic corticoids, selective use of drains, polyglycolic acid mesh, reinforced staplers, and collagen enhanced thrombin sealant. Conclusions: Studies reporting successful strategies show considerable heterogeneity in both the included populations and the way the strategies were applied. A personalized approach based on the risk of developing fistula and specific pancreatic features may be beneficial and should be further explored in future randomized clinical trials. Full article

The intravenous low-dose dexamethasone suppression test (IV-LDDST) is considered the most accurate method for diagnosing Cushing’s syndrome (CS) in dogs, but its intravenous administration and repeated hospital sampling are stressful and time-consuming for both dogs and owners. This study evaluated an oral LDDST (O-LDDST) as a minimally invasive alternative. The approach is based on the urinary corticoid-to-creatinine ratio (uCC) measured in urine samples collected at home at baseline (B-uCC) and 8 h after administering a low oral dose of dexamethasone (0.01 mg/kg; 8h-uCC). A total of 168 client-owned dogs were prospectively recruited: 42 healthy dogs (HD), 40 dogs with disease mimicking CS (DMCS), and 86 dogs with confirmed CS. An ROC curve analysis showed that dogs with CS had significantly higher B-uCC and 8h-uCC and a lower suppression percentage (%S) compared with HD and DMCS (all p < 0.0001). Optimal cut-offs were B-uCC > 14.2 × 10⁻⁶, 8h-uCC > 6.7 × 10⁻⁶, and %S < 48.6%, yielding sensitivity/specificity of 82.9%/83.3%, 95.3%/92.6%, and 86.0%/85.3%, respectively. O-LDDST was preferred by 85.9% of owners, although it did not distinguish pituitary- from adrenal-dependent CS. The O-LDDST proved to be a reliable, accurate, and minimally invasive diagnostic option for CS in dogs, with 8h-uCC providing the highest accuracy. Full article

This retrospective study aimed to evaluate the survival rate of hybrid dental implants in different patient profiles and clinical conditions. A total of 1215 patients’ files were analyzed from patients with at least one hybrid dental implant inserted at ILAPEO College (Curitiba, Brazil) from 2018 to 2024. The data collection was performed from 2021 to 2024. Parameters related to patients, implants, and surgical characteristics were collected. Descriptive summary statistics were estimated for all parameters. The associations between the dependent variables “implant survival” and patient, procedure, and implant characteristics were assessed by the Cox proportional hazards model. A total of 4783 hybrid dental implants (Helix, GM, Neodent) were placed in 1215 patients with a mean age of 57.17 ± 12.09 years. The most frequent patients’ medical conditions were diabetes, hypertension, thyroid dysfunction, use of steroids (corticoids), psychological limitations, and bruxism and clenching. Patients were followed for a mean period of 29.54 ± 18.95 months. Immediate loading was applied in 2302 (48.13%) implants and conventional loading in 1735 (36.27%). One hundred and fifty-one implants were lost due to a lack of osseointegration, resulting in an implant survival rate of 95.4% (CI: 94.4%; 96.6%). Adverse events were reported in 389 (8.13%) implants. Uncontrolled hypertension, hypertension without information on control, absence of final abutment, replacement implant, and adverse event occurrence were associated with implant loss. Treatment using a hybrid macrogeometry dental implant is an option for total or partial edentulous patients with compromised health and different clinical conditions. Full article

Cortisol follows a 24 h circadian rhythm that plays a pivotal role in maintaining the optimal function of various physiological systems in alignment with behavioural cycles. Its synthesis and secretion are regulated by the hypothalamic–pituitary–adrenal (HPA) axis. The 24 h fluctuations of cortisol may result from physiological changes influencing its regulation, or conversely, hormone-mediating physiological changes within the body. This review mainly aims to synthesize current evidence on methods for detecting cortisol. In addition, it focuses on evaluating cortisol’s potential as a biomarker for circadian disruption and related health impacts. A literature search was conducted across databases, including Google Scholar, PubMed, and Scopus, using search terms such as “circadian rhythm OR circadian clock OR circadian disruption OR circadian dysregulation” and “cortisol OR hydrocort* OR corticoid OR corticosteroid”. A total of 47 articles were included on methods of cortisol detection, and 41 articles were reviewed for their health implications. Cortisol measured via saliva, blood serum, urine, interstitial fluid (ISF), and sweat has been reported as suitable for 24 h monitoring, reflecting circadian regulation. In contrast, hair cortisol is suitable for identifying chronic changes and prolonged elevations in cortisol levels. This review highlights the stability, suitability, and challenges of each detection method, including reported cortisol levels across studies. Additionally, it provides a comprehensive overview of health implications associated with changes in cortisol, offering insights into its potential as a marker for circadian disruption and related health outcomes. Full article

Background: Immunomodulatory treatments targeting excessive host immune responses favorably shifting the course of COVID-19. High doses of calcifediol may reduce the mortality of this infection. Objective: To evaluate how a high dose of calcifediol modifies the risk of death in patients hospitalized with COVID-19 during the first outbreaks. Design: A retrospective, observational study to evaluate the relationship between treatment with calcifediol and the risk of death in patients hospitalized with COVID-19 at the “Complejo Hospitalario Universitario de Albacete” (CHUA), Spain, during the months of January to March 2021. Patients were treated with corticosteroids, and some patients also received baricitinib and/or high doses of calcifediol, according to CHUA’s therapeutic protocol 2021 for COVID-19. The primary outcome measure was mortality according to calcifediol treatment. Results: A total of 230 patients were included. 25(OH)D levels were measured on admission in 148 patients, showing a high prevalence of vitamin D deficiency [median 25(OH)D: 17.5 ng/mL]. Thirty-four (23%) had severe deficiency (25(OH)D ≤ 10 ng/mL). In the 119 patients (51.7%) who received in-hospital treatment with a high dose of calcifediol, the mortality rate was 12.6% (15 cases, 95% confidence interval [CI], 7.8–19.8%), while in 111 patients who did not receive treatment with calcifediol, the death rate was 23.4% (26 cases, 95% CI: 16.5–32.1%; p = 0.039). The odds ratio (OR) in treated vs. untreated patients was 0.47 (95% CI: 0.23–0.95). Among the patients admitted with severe deficiency, 16 received treatment with calcifediol, with a mortality rate of 0.0% (0 cases, 95% CI: 0.0–19.4%), while in the 18 not treated with calcifediol, a death rate of 38.9% was observed (7 cases, 95% CI: 20.3–61.4%; p = 0.008). The mortality rate was lower in patients treated with the combination of calcifediol and corticosteroids vs. those treated with corticosteroids alone (p = 0.038) and vs. those treated with corticosteroids and baricitinib (p = 0.033). Conclusions: In the ALBACOVIDIOL study, calcifediol treatment was associated with a lower observed mortality rate in hospitalized patients with COVID-19 treated with corticosteroids (with or without baricitinib), especially in those with severe vitamin D deficiency. Causality cannot be inferred due to the retrospective study design. (Public database: ClinicalTrials.gov, NCT05819918). Full article

Background/Objectives: The COVID-19 pandemic resulted in 675 million cases and 6.9 million deaths by 2022. Despite substantial declines in case fatalities following widespread vaccination campaigns, the threat of future coronavirus outbreaks remains a concern. Current treatments for COVID-19 have been repurposed from existing therapies for other infectious and non-infectious diseases. Emerging evidence suggests a role for genetic factors in both susceptibility to SARS-CoV-2 infection and response to treatment. However, comprehensive studies correlating clinical outcomes with genetic variants are lacking. The main aim of our study is the identification of host genetic biomarkers that predict the clinical outcome of COVID-19 pharmacological treatments. Methods: In this study, we present findings from GWAS and candidate gene and pathway enrichment analyses leveraging diverse patient samples from the Spanish Coalition to Unlock Research of Host Genetics on COVID-19 (SCOURGE), representing patients treated with immunomodulators (n = 849), corticoids (n = 2202), and the combined cohort of both treatments (n = 2487) who developed different outcomes. We assessed various phenotypes as indicators of treatment response, including survival at 90 days, admission to the intensive care unit (ICU), radiological affectation, and type of ventilation. Results: We identified significant polymorphisms in 16 genes from the GWAS and candidate gene studies (TLR1, TLR6, TLR10, CYP2C19, ACE2, UGT1A1, IL-1α, ZMAT3, TLR4, MIR924HG, IFNG-AS1, ABCG1, RBFOX1, ABCB11, TLR5, and ANK3) that may modulate the response to corticoid and immunomodulator therapies in COVID-19 patients. Enrichment analyses revealed overrepresentation of genes involved in the innate immune system, drug ADME, viral infection, and the programmed cell death pathways associated with the response phenotypes. Conclusions: Our study provides an initial framework for understanding the genetic determinants of treatment response in COVID-19 patients, offering insights that could inform precision medicine approaches for future epidemics. Full article

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (PH-HFpEF) represents a frequent form of PH related to left ventricular dysfunction. The pathophysiology of PH-HFpEF is intricate, and varied and includes vascular, cardiac, and pulmonary factors that contribute synergistically to developing this clinical syndrome. Improved knowledge of the pathophysiology of PH-HFpEF has paved the way for the use of new drugs such as angiotensin receptor neprilysin inhibitors (ARNIs), non-steroidal mineral corticoid receptor antagonist (nsMRA), sodium-glucose cotransporter inhibitors (SGLT2is), levosimendan, and glucagon-like peptide 1 (GLP-1) agonists. ARNIs are a widely used drug for the treatment of PH associated with heart failure with reduced ejection fraction. They have also recently been used in PH-HFpEF patients with hemodynamic benefits that need to be confirmed in future research. Finerenone is an innovative non-steroidal mineralocorticoid receptor antagonist that exhibits notable cardioprotective and renoprotective properties in individuals suffering from chronic diabetic kidney disease. It also enhances outcomes for patients with heart failure, whether they have mildly reduced or preserved ejection fraction. Moreover, in experimental studies, finerenone has been found to lower pulmonary artery pressure, reduce muscularization, and decrease the wall thickness of pulmonary arteries. SGLT2i have revolutionized the treatment of patients with heart failure irrespective of left ventricular ejection fraction, and their treatment is also associated with an improvement in the hemodynamics profile in patients with PH-HFpEF. Levosimendan is a widely used inodilator in the treatment of acute and advanced heart failure. In addition, its use in patients with PH-HFpEF (supported by the positive effects on pulmonary hemodynamics that levosimendan exerts) has recently demonstrated hemodynamic benefit in a small phase 2 study that paved the way for phase 3 studies and the creation of an oral formulation of levosimendan. Finally, GLP1 agonists are a class of drugs that, in preliminary evidence, have shown a positive effect on cardiac hemodynamics, mainly by facilitating left ventricular unloading. These effects, along with the reduction in insulin resistance and weight loss, likely lead to beneficial outcomes for PH-HFpEF patients, especially those with obesity as a comorbidity. Full article

Background/Objectives: Fetal spina bifida (fSB) is the most common neural tube defect, and intrauterine repair has become a valid treatment option for selected cases. If fSB repair is offered, the ideal time for surgery is from 24 to 26 gestational weeks (GWs). The preoperative steroids for lung maturation and preoperative tocolytics that are administered are known to increase the prevalence of gestational diabetes (GD), which normally occurs in about 10–15% of all pregnant women. This study assessed the prevalence, possible influencing factors, and consequences on the course of pregnancy regarding GD in this cohort. Methods: Between 2010 and 2022, 184 fSB cases were operated. Those patients operated on after 24 0/7 GWs received steroids before surgery. All the patients received tocolysis, and an oral glucose tolerance test was performed between 26 and 28 GWs at least 7 days after steroid administration. In 2020, we established an early postoperative mobilization protocol. The perioperative management procedures of those patients with and without GD were compared to each other, and also, the patients treated according to the early mobilization protocol were compared to the remaining cohort. Results: Nineteen percent were diagnosed with GD. Corticosteroids were administered in 92%. Neither the corticoid administration nor the interval between the administration and glucose tolerance test was different in patients with or without GD. Further, 99.5% received postoperative tocolytics for at least 48 h. The women with GD had significantly longer administration of tocolytics. The length of stay (LOS) was higher in those patients with GD. The gestational age (GA) at delivery was significantly lower in the cohort with GD. In the early mobilized group, we found a significantly higher GA at delivery (37.1 GWs vs. 36.2 GWs, p = 0.009) and shorter LOS (p < 0.001), and their GD rate was lower (10% vs. 20%), although not statistically significant. Conclusions: The GD incidence in the women after fSB repair was higher than in the usual pregnant population. Early mobilization, rapid tocolytics decrease, and shorter LOS could benefit the pregnancy course after fSB repair and may decrease the risk for GD in this already high-risk cohort without increasing the risk for preterm delivery. Full article

Quantitative systems pharmacology (QSP) models are rarely applied prospectively for decision-making in clinical practice. We therefore aimed to operationalize a QSP model for potas-sium homeostasis to predict potassium trajectories based on spironolactone administrations. For this purpose, we proposed a general workflow that was applied to electronic health records (EHR) from patients treated in a German tertiary care hospital. The workflow steps included model exploration, local and global sensitivity analyses (SA), identifiability analysis (IA) of model parameters, and specification of their inter-individual variability (IIV). Patient covariates, selected parameters, and IIV then defined prior information for the Bayesian a posteriori prediction of individual potassium trajectories of the following day. Following these steps, the successfully operationalized QSP model was interactively explored via a Shiny app. SA and IA yielded five influential and estimable parameters (extracellular fluid volume, hyperaldosteronism, mineral corticoid receptor abundance, potassium intake, sodium intake) for Bayesian prediction. The operationalized model was validated in nine pilot patients and showed satisfactory performance based on the (absolute) average fold error. This provides proof-of-principle for a Prescribing Monitoring of potassium concentrations in a hospital system, which could suggest preemptive clinical measures and therefore potentially avoid dangerous hyperkalemia or hypokalemia. Full article

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. Objective: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. Design, patients and setting: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). Interventions: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. Measurements: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. Results: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. Interpretation: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation. Full article

Budesonide is a mineral corticoid applied in the local therapy of pediatric atopic dermatitis. Unfortunately, its dermal administration is hindered by the concomitant adverse effects and its physicochemical properties. The characteristic pH change in the atopic lesions can be utilized for the preparation of a pH-sensitive nanocarrier. In this view, the formulation of Eudragit L 100 nanoparticles as a budesonide delivery platform could provide more efficient release to the desired site, improve its penetration, and subsequently lower the undesired effects. In this study, budesonide-loaded Eudragit L100 nanoparticles were prepared via the nanoprecipitation method (mean diameter 57 nm, −31.2 mV, and approx. 90% encapsulation efficiency). Their safety was proven by cytotoxicity assays on the HaCaT keratinocyte cell line. Further, the drug-loaded nanoparticles were incorporated into two types of hydrogels based on methylcellulose or Pluronic F127. The formulated hydrogels were characterized with respect to their pH, occlusion, rheology, penetration, spreadability, and drug release. In conclusion, the developed hydrogels containing budesonide-loaded nanoparticles showed promising potential for the pediatric treatment of atopic dermatitis. Full article

Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number of publications on EBV encephalitis mainly document isolated clinical cases. This study aimed to summarize published data on EBV encephalitis. A systematic literature search identified 97 EBV encephalitis cases. In the selected cases, EBV-related neurological disorders manifested as lymphocytic pleocytosis in the cerebrospinal fluid (CSF) with moderate hyperproteinorachia. The EBV PCR test was positive in 87% of the CSF samples, with wide-ranging viral loads. When encephalitis occurred in the context of past EBV infections, all of the EBV PCR tests on CSF samples were positive. On the contrary, negative EBV PCR tests on CSF samples occurred only in the context of primary infections. EBV PCR was rarely carried out on blood samples, contributing minimally to the diagnosis. For the treatment of EBV encephalitis, Aciclovir was used alone in 29% of cases, and in association with other drugs in 40% of cases. Ganciclovir (30%), corticoids (52%), and immunoglobulins (15%) were mainly used in association with other drugs. Cerebral imaging was abnormal in 69% of cases, mostly in the cerebellum and basal ganglia. This work highlights that the EBV PCR test on CSF samples is currently the main laboratory diagnostic test to diagnose EBV encephalitis. This diagnostic test is useful; however, it is imperfect. New complementary diagnostic tools, approved treatments, and standardized practices could improve patient management. Full article

Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. To address this, a comprehensive review was conducted, analyzing 30 recent papers from databases PubMed, CAPES journals, and the Virtual Health Library (VHL). The studies encompassed a wide range of therapeutic approaches, including antiretrovirals, immunomodulators, antineoplastics, amino acids, antiparasitics, and even natural products and plant extracts. Notably, the category with the highest number of articles was related to drugs for the treatment of ATLL. Studies employing mogamulizumab as a new perspective for ATLL received greater attention in the last 5 years, demonstrating efficacy, safe use in the elderly, significant antitumor activity, and increased survival time for refractory patients. Concerning HAM/TSP, despite corticosteroid being recommended, a more randomized clinical trial is needed to support treatment other than corticoids. The study also included a comprehensive review of the drugs used to treat disseminated strongyloidiasis in co-infection with HTLV-1, including their administration form, in order to emphasize gaps and facilitate the development of other studies aiming at better-directed methodologies. Additionally, docking molecules and computer simulations show promise in identifying novel therapeutic targets and repurposing existing drugs. These advances are crucial in developing more effective and targeted treatments against HTLV-1 and its related diseases. Full article

Idiopathic recurrent pericarditis (IRP) can be the hallmark of an autoinflammatory syndrome with recurrent attacks of chest pain and symptom-free intervals following an acute episode. The recurrence rate may be 35% in the pediatric population, frequently with less severe manifestations than at the first episode. Pericarditis can be the sole clinical manifestation or may be part of a systemic autoinflammatory disease (SAID), especially in the case of a recurrence. Familial Mediterranean Fever (FMF), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Mevalonate-Kinase Deficiency (MKD), nucleotide-binding oligomerization domain 2 (NOD2)-associated autoinflammatory syndrome, and others are closely related to IRP based on similar clinical manifestations and treatment responses to anti-interleukin 1 (IL-1) agents, such as anakinra, and should therefore be excluded in patients with IRP. A newly described SAID, an autosomal dominant disorder known as NLRP12-AID (nucleotide-binding leucine-rich repeat-containing receptor 12-related autoinflammatory disease) is caused by heterozygous mutations in the NLRP12 gene and most commonly affects children. Fewer than 40 pediatric patients with NLRP12-AID have been described in the medical literature, with none presenting with RP. We report a case of relapsing pericarditis responsive to anti-IL-1 therapy in a male adolescent who carried a missense mutation in the NLRP12 gene potentially causative of the excessive activation of inflammatory pathways. This is a unique case in the medical literature that associates recurrent pericarditis in an adolescent presumed to be related to the missense mutation in the NLRP12 gene. The role of the NLRP12 inflammasome in generating and maintaining recurrent pericardial inflammation should be considered. Full article

Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient’s adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs. Full article