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Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH). To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH. A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance. Both iloprost doses failed to improve six-minute walking distance (p = 0.36). Low dose iloprost (estimated difference of the means -1.0%, p = 0.035) as well as high dose iloprost (-2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p = 0.002 and p = 0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (-76 ml/min, p = 0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p = 0.040) and impaired ventilation during exercise (-3.0l/min, p<0.001). Improvement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely. Controlled-Trials.com ISRCTN61661881.

Background Part of the pathophysiology in septic shock is a progressive activation of the endothelium and platelets leading to widespread microvascular injury with capillary leakage, microthrombi and consumption coagulopathy. Modulating the inflammatory response of endothelium and thrombocytes might attenuate this vicious cycle and improve outcome. Method The CO-ILEPSS trial was a randomised, placebo-controlled, double-blind, pilot trial. Patients admitted to the intensive care unit with septic shock were randomised and allocated in a 2:1 ratio to active treatment with dual therapy of iloprost 1 ng/kg/min and eptifibatide 0.5 μg/kg/min for 48 h or placebo. The primary outcomes were changes in biomarkers reflecting endothelial activation and disruption, platelet consumption and fibrinolysis. We compared groups with mixed models, post hoc Wilcoxon signed-rank test and Mann-Whitney U test. Results We included 24 patients of which 18 (12 active, 6 placebo) completed the full 7-day trial period and were included in the per-protocol analyses of the primary outcomes. Direct comparison between groups showed no differences in the primary outcomes. Analyses of within-group delta values revealed that biomarkers of endothelial activation and disruption changed differently between groups with increasing levels of thrombomodulin ( p  = 0.03) and nucleosomes ( p  = 0.02) in the placebo group and decreasing levels of sE-Selectin ( p  = 0.007) and sVEGFR1 ( p  = 0.005) in the active treatment group. Platelet count decreased the first 48 h in the placebo group ( p  = 0.049) and increased from baseline to day 7 in the active treatment group ( p  = 0.023). Levels of fibrin monomers declined in the active treatment group within the first 48 h ( p  = 0.048) and onwards ( p  = 0.03). Furthermore, there was a significant reduction in SOFA score from 48 h ( p  = 0.024) and onwards in the active treatment group. Intention-to-treat analyses of all included patients showed no differences in serious adverse events including bleeding, use of blood products or mortality. Conclusion Our results could indicate benefit from the experimental treatment with reduced endothelial injury, reduced platelet consumption and ensuing reduction in fibrinolytic biomarkers along with improved SOFA score. The results of the CO-ILEPSS trial are exploratory and hypothesis generating and warrant further investigation in a large-scale trial. Trial registration Clinicaltrials.com, NCT02204852 (July 30, 2014); EudraCT no. 2014-002440-41

The aim of the work was the synthesis of a new 28-acetylbetulin derivative containing an ester group with a carbon–carbon triple bond in the C3 position. To obtain the title compound, a reaction of 28-acetylbetulin with but-2-ynoic acid was carried out according to the Steglich method. The synthetized compound was fully characterized by analyzing the nuclear magnetic resonance spectra ([sup.1]H-NMR, [sup.13]C-NMR), as well as the heteronuclear single quantum coherence (HSQC), and by conducting a heteronuclear multiple bond coherence (HMBC) experiment. Infrared (IR) spectroscopy and high-resolution mass spectrometry (HRMS) were also performed. Additionally, pharmacokinetic parameters and drug similarity of the studied molecule were calculated using in silico methods.

Background. We present the case of a 75-year-old patient with a past medical history of melanoma removed in 2020, type 2 diabetes mellitus, cognitive decline evolving into Lewy body dementia, and IgG-lambda MGUS (0.5 g/dL) under hematological follow-up.   Case Report. Starting in 2020, the patient reported the recurrent appearance of small, subcentimeter ulcers on the fingers, which resolved spontaneously within a few weeks, and an isolated episode of frank purpura on the lower limbs, which subsequently evolved into dyschromic scars. In the rheumatological field, immunological and instrumental tests were performed (capillaroscopy, echocardiogram, ANA, ENA, ANCA, ACPA, antiphospholipids, RF, C3/C4, PCR, serologies for HBV and HCV, Bence Jones proteinuria), all of which were within normal limits. In this context, the presence of a 6% cryocrit was documented, composed of monoclonal IgM-lambda cryoglobulin (2%) and cryofibrinogen (4%). Subsequent hematological investigation with flow cytometry documented a circulating T-LGL population (30%), with no evidence of clonality on bone marrow biopsy, nor signs of myelodysplasia. In the absence of criteria for overt lymphoproliferative disease, there was no indication for specific treatment. In the following years, subcentimeter digital lesions continued to appear episodically, always self-limiting, without deep ulcerations or purpuric recurrences. However, in early 2025, following reported exposure to low temperatures, a sudden worsening was observed, with the appearance of crusted ulcers on the lower limbs, not consistent with vascular distribution. The major lesions were located on the lateral surface of both legs (up to 4 cm in diameter), on the heels, and on some toes. The patient initially reported home management without benefit. A lower extremity ECD was negative for occlusive changes. A skin biopsy of a lesion on the right heel showed partial epidermal ulcerative necrosis, hyperkeratosis, epidermal hyperplasia, and in the dermis, scar-like fibrosis, reactive vascular proliferation, and minimal lymphocytic inflammation, with no histological evidence of vasculitis. The patient arrived at the Difficult Wounds service of the Rheumatology unit in February 2025. Considering the comorbidities, the histological picture, and the high-titer cryofibrinogen, monthly therapy with Iloprost via continuous infusion was initiated, along with advanced local wound care. Progressive resolution of the lesions was observed by May 2025, with good tolerance to the therapy and no apparent clinical recurrences.   Conclusions. Iloprost represents an effective and well-tolerated therapeutic option for the treatment of ulcers associated with cryofibrinogenemia, especially in fragile patients for whom the use of immunosuppressants is risky or contraindicated. In complex cases, multidisciplinary discussion is confirmed to be crucial for a correct diagnostic assessment and targeted management.  

An increasingly recognized prognostic factor for out-of-hospital-cardiac-arrest (OHCA) patients is the ischemia-reperfusion injury after restored blood circulation. Endothelial injury is common in patients resuscitated from cardiac arrest and is associated with poor outcome. This study was designed to investigate if iloprost infusion, a prostacyclin analogue, reduces endothelial damage in OHCA patients. 50 patients were randomized in a placebo controlled double-blinded trial and allocated 1:2 to 48-hours iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Endothelial biomarkers (soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), vascular endothelial cadherine (VEcad), nucleosomes) and sympathoadrenal activation (epinephrine/norepinephrine) from baseline to 48 and 96-hours were evaluated. Iloprost infusion did not influence endothelial biomarkers by the 48-hour endpoint. A rebound effect was observed with higher biomarker plasma values in the iloprost group (sTM p=0.02; Syndecan p=0.004; nucleosomes p<0.001; VEcad p<0.03) after 96-hours. There was a significant difference in 180-day mortality in favor of placebo. There was no difference regarding total adverse events between groups (p=0.73). Two patients were withdrawn in the iloprost group due to hypotension. The administration of low-dose iloprost (1ng/kg/min) to OHCA patients did not significantly influence endothelial biomarkers as measured by the 48- hour endpoint. A rebound effect was however observed in the 96-hour statistical model, with increasing endothelial biomarker levels after cessation of the iloprost-infusion.

The number of effective, long-term treatments for pulmonary hypertension is limited. In this double-blind, randomized trial, an aerosolized form of iloprost, a stable analogue of the pulmonary vasodilator prostacyclin, was assessed over a 12-week period. Iloprost had a beneficial effect on the combined end point of the distance walked in six minutes and an improvement in the New York Heart Association functional class. A continuous infusion of prostacyclin was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. 1 However, its use is associated with a number of serious drawbacks. The lack of pulmonary selectivity results in systemic side effects, tolerance leads to progressive increases in the dose, and there may be recurrent infections of the intravenous catheter. 2 As an alternative, inhaled nitric oxide possesses pulmonary selectivity, but it is less potent than prostacyclin in the pulmonary vasculature. 3 , 4 Moreover, an interruption in the inhalation of continuous nitric oxide may cause rebound pulmonary hypertension. 5 , 6 Designed . . .

Background Proximal humerus fractures (PHFs) are the third most common fractures in elderly patients. Over 70% of PHFs in patients aged over 60 are displaced fractures, often necessitating surgical treatment. However, osteosynthesis is associated with a high rate of complications, highlighting the urgent need for additional therapeutic approaches to enhance bone healing and prevent osteonecrosis. This study evaluates the safety, feasibility and potential efficacy of local prostacyclin (iloprost) to improve bone healing in patients with PHFs. Methods Thirty eligible patients will be randomized into one of three groups at a 1:1:1 ratio. All patients will receive angular stable locking plate fixation. Two treatment groups will receive an additional single dose of local iloprost through a 24-hour infusion postoperatively (group 1: low dose; group 2: high dose), while the control group will only receive the osteosynthesis. Patients will be monitored for 52 weeks. The primary endpoint is safety, with secondary endpoints including the preservation of the screw tip apex distance as an indicator of fracture healing, head shaft angle, necrosis rate, and patient-related outcome measures. Discussion The Ilobone study aims to provide data on the potential for biological augmentation of osteosynthesis procedures in PHFs, prone to healing challenges and complications. Trial registration The trial is registered with ClinicalTrial.gov (NCT04543682), registered 02 Sep. 2020, https://clinicaltrials.gov/show/NCT04543682 and the German Clinical Trials Registry (DRKS00027081), registered 10 Nov. 2021 https://drks.de/search/de/trial/DRKS00027081 .

Background. To evaluate the safety and perceived efficacy of home-based prostacyclin analogue infusions compared with hospital administration in patients with vascular manifestations of the Scleroderma Spectrum.   Methods: In 2019, a pilot program for home-based Iloprost infusions was launched at the Local Health Authority (ASL) of Pescara. We performed a retrospective 6-year analysis including patients receiving home therapy for at least 6 months. Patients completed a structured questionnaire assessing: • frequency of vascular manifestations, • comparison between home (EL) and hospital (DH) administration in terms of side effects, • acceptability and overall impact of home treatment. Blood pressure values were collected before, during, and after each home infusion.   Results. Thirty-four patients were included. Most reported subjective improvement of Raynaud’s phenomenon. A moderate positive correlation (ρ ≈ 0.47) was observed between the duration of home treatment and perceived benefit. Among the 5 patients with active digital ulcers, 4 reported improvement. Only two patients had pulmonary arterial hypertension; therefore, no conclusions were drawn for this subgroup. Eight side effects were evaluated on a 0–3 scale. Nausea, flushing, and headache were significantly reduced during home treatment (p < 0.05), while hypotension and diarrhea showed no significant differences. Elastomer pump acceptability was high: 100% of patients judged it easy to handle, 97% felt safe using it, and 88% reported improved quality of life. Regarding hemodynamic effects, systolic blood pressure showed a significant reduction during infusion (−4.6 mmHg; p = 0.0015) followed by recovery afterwards (+3.1 mmHg; p = 0.011). Diastolic pressure changes were milder, with a slight decline during infusion (−1.5 mmHg; p = 0.083) and a significant increase at the end (+2.8 mmHg; p = 0.026). Mean arterial pressure varied transiently and was well tolerated. Only one patient showed marked variability, suggesting the need for individualized monitoring in unstable cases.   Conclusions. Home-based prostacyclin analogue infusions appear safe, well tolerated, and associated with high patient acceptance in the Scleroderma Spectrum. These findings support the implementation of home Iloprost therapy as an integral component of vascular management in this population.

Background Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90-day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS. Trial registration EUDRA-CT: 2016-003168-37. Registered on 12 April 2017. ClinicalTrials.gov : NCT03111212 . Registered on 4 June 2017.