Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs.

Introduction: Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock. Methods: In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05). Results: The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage. Conclusion: The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Effective control of refractory pulmonary hypertension with iloprost inhalation in an infant with congenital absence of the right pulmonary artery: a case report.

Unilateral absence of the pulmonary artery is a rare congenital cardiovascular anomaly that can lead to pulmonary hypertension and poor outcomes. We report the case of a 1-month-old infant with isolated unilateral absence of the pulmonary artery and severe pulmonary hypertension on the right and left sides, respectively. The patient was unresponsive to multiple medications for pulmonary hypertension, and surgical revascularisation was unfeasible. However, iloprost inhalation was effective.

Prostacyclin in trauma patients with hemorrhagic shock: A randomized clinical trial.

BACKGROUND: A main cause of trauma morbidity and mortality is multiple-organ failure, and endotheliopathy has been implicated. Pilot studies indicate that low-dose prostacyclin improves endothelial functionality in critically ill patients, suggesting that this intervention may improve trauma patient outcome. METHODS: We conducted a multicenter, randomized, blinded, clinical investigator-initiated trial in 229 trauma patients with hemorrhagic shock who were randomized 1:1 to 72 hours infusion of the prostacyclin analog iloprost (1 ng/kg/min) or placebo. The primary outcome was the number of intensive care unit (ICU)-free days alive within 28 days of admission. Secondary outcomes included 28-day all-cause mortality and hospital length of stay. RESULTS: The mean number of ICU-free days alive within 28 days was 15.64 days in the iloprost group versus 13.99 days in the placebo group (adjusted mean difference, -1.63 days [95% confidence interval (CI), -4.64 to 1.38 days]; p = 0.28). The 28-day mortality was 18.8% in the iloprost group versus 19.6% in the placebo group (odds ratio, 1.01 [95% CI, 0.51-2.0]; p = 0.97). The mean hospital length of stay was 19.96 days in the iloprost group versus 27.32 days in the placebo group (adjusted mean difference, 7.84 days [95% CI, 1.66-14.02 days], p = 0.01). CONCLUSION: Iloprost did not result in a statistically significant increase in the number of ICU-free days alive within 28 days of admission, whereas it was safe and a statistically significant reduction in hospital length of stay was observed. Further research on prostacyclin in shocked trauma patients is warranted. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Real life use of prostacyclin analog (iloprost), a multi-centric survey data from the Scleroderma study group Emilia Romagna (Sclero-RER) and review of the literature.

BACKGROUND AND AIM: Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out. RESULTS: All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses). CONCLUSIONS: These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

Congenital Isolated Unilateral Agenesis of Pulmonary Arteries with 3-Year Follow-Up after Initiation of Treatment.

Background and objective: Unilateral agenesis of pulmonary arteries (UAPA) is a rare disease, with approximately 400 cases reported to date. UAPA is often associated with congenital heart disease, and the uncomplicated form is isolated UAPA, which accounts for approximately 30% of all cases of UAPA. The incidence of pulmonary hypertension due to UAPA has been reported to range from 19 to 44%. There is no consensus treatment for pulmonary hypertension associated with UAPA. We present the first reported case in which a three-drug combination, comprising of iloprost inhalation, riociguat, and ambrisentan, was administered to a patient with UAPA, and was followed-up for 3 years post-diagnosis. Case presentation: A 68-year-old Japanese woman presented to our hospital with dyspnea and chest discomfort. She underwent chest radiography, blood tests, and echocardiography; however, the cause of the patient's symptoms could not be identified. During regular follow-up, an echocardiography 21 months after the initial visit revealed elevated right ventricular pressure (peak tricuspid regurgitation velocity: 5.2 m/s and right ventricular systolic pressure: 120 mmHg) and a diagnosis of pulmonary hypertension was made. Contrast-enhanced computed tomography (CT) of the chest and a pulmonary blood flow scintigram were performed to investigate the cause of pulmonary hypertension, and isolated UAPA was diagnosed. The patient was treated with a three-drug combination of iloprost inhalation, riociguat, and ambrisentan and followed up for 3 years with good therapeutic outcomes. Conclusions: We present a case of pulmonary hypertension caused by isolated UAPA. Although rare, this disease can lead to pulmonary hypertension and should be treated cautiously. While there is no consensus regarding the treatment of this disease, a three-drug combination of iloprost inhalation, riociguat, and oral ambrisentan proved effective.

The effect of using iloprost on prognosis in COVID-19 patients with ARDS: a retrospective clinical study.

OBJECTIVE: Epithelial damage together with endothelitis and microvascular thrombi are responsible for COVID-19 associated acute respiratory distress syndrome (ARDS). Iloprost, improves endothelial damage and reduces thrombotic complications with its vasodilator, anti-platelet, anti-inflammatory, and anti-fibrotic effects. In our study, we aimed to determine the effect of iloprost on oxygenation, hemodynamics, weaning, and mortality in severe COVID-19 ARDS. PATIENTS AND METHODS: This was a retrospective study conducted in a pandemic hospital in the city of Istanbul, Turkey. Patients, with severe COVID-19 ARDS, who were receiving iloprost for seven days were included in the study. The demographic data, APACHE II, and SOFA (Sequential Organ Failure Assessment score) scores (at admission and discharge), pH, PaO2, PCO2, SatO2, lactate, PaO2/FiO2 (inspiratory fractionated oxygen), respiratory rate-oxygenation (ROX) index (peripheral oxygen saturation/fraction of inhaled oxygen), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressures (MAP), heart rate (HR) values were recorded before starting iloprost (T0), and on days of iloprost administration (2.0 nanograms/kg/minute/6 hours/day) (T1, T2, T3, T4, T5, T6, T7), and the day after last day of iloprost administration (Tfinal). Also, mortality was recorded in a retrospective manner. Two groups were formed according to mortality (Group M) and discharge (Group D). RESULTS: A total of 22 patients (16 men, 6 women) were evaluated. Age, APACHE II, SOFA scores were higher in Group M. The lactate value at T1-3-4-5-7 was lower than T0 in both groups. PaO2 value between T2-Tfinal was higher than T0. A statistically significant increase was found in PaO2/FiO2 levels in both groups. The PaO2/FiO2value between T5-Tfinal was significantly lower in Group M compared to Group D. ROX index was significantly higher between T4-Tfinal when compared with T0. CONCLUSIONS: Iloprost improves oxygenation but has no effect on mortality in COVID-19 ARDS.

A review of the development of gangrene in patients with systemic lupus erythematosus - A 44-year follow-up study.

OBJECTIVES: This review addresses the question of what happens long-term to those systemic lupus erythematosus (SLE) patients who develop gangrene. It also seeks to find common clinical and serological features, risk factors and triggers and how best to manage this challenging complication. METHODS: We reviewed 850 patients with SLE attending a UK tertiary referral center, followed up over 44 years, assessing their demographics, clinical and serological features, treatment in the acute phase, their long-term outcome and long-term management. RESULTS: Ten out of 850 patients (1.2%) developed gangrene; the mean age of onset was 17 years (range 12-26 years) Eight out of 10 patients had a single episode of gangrene. One of the other two was not willing to have anticoagulation. The first episode of gangrene ranged from presentation to 32 years after SLE onset, mean duration of SLE at the onset of the gangrene was 18.5 years SD 11.5 years. Anti-phospholipid (PL) antibodies were over-represented in the patients with gangrene. All had active SLE at the time the gangrene developed. All patients were treated with intravenous (IV) iloprost infusions, and the antiphospholipid-antibody positive patients were anti-coagulated, most staying on long term anticoagulation. Underlying possible triggers were treated appropriately. Two patients who did not respond to the initial treatment needed further immunosuppression. All patients suffered digit loss. CONCLUSION: Although rare, gangrene is a sinister, potentially late developing complication of SLE, it rarely recurs. It is associated with anti-phospholipid antibodies, active disease, and other possible triggers such as infection and cancer. Anticoagulation therapy, steroids and iloprost, and further immunosuppression may be needed to stop the evolution of gangrene.

Can iloprost be used for treatment of cold weather injury at the point of wounding in a forward operating environment? A literature review.

INTRODUCTION: Cold Weather Injury (CWI) represents a spectrum of pathology, the two main divisions being Freezing Cold Injury (FCI) and Non-Freezing Cold Injury (NFCI). Both are disabling conditions associated with microvascular and nerve injury often treated hours after initial insult when presenting to a healthcarestablishment. Given that iloprost is used for the treatment of FCI, could it be used in a forward operating environment to mitigate treatment delay? Is there a role for its use in the forward treatment of NFCI? This review sought to evaluate the strength of evidence for the potential use of iloprost in a forward operating environment. METHODS: Literature searches were undertaken using the following question for both FCI and NFCI: in [patients with FCI/NFCI] does [the use of iloprost] compared to [standard care] reduce the incidence of [long-term complications]. Medline, CINAHL and EMBASE databases were searched using the above question and relevant alternative terminology. Abstracts were reviewed before full articles were requested. RESULTS: The FCI search yielded 17 articles that were found to refer to the use of iloprost and FCI. Of the 17, one referred to pre-hospital treatment of frostbite at K2 base camp; however, this was utilising tPA. No articles referred to pre-hospital use in either FCI or NFCI. DISCUSSION: Although evidence exists to support the use of iloprost in the treatment of FCI, its use to date has been in hospital. A common theme is delayed treatment due to the challenges of evacuating casualties from a remote location. There may be a role for iloprost in the treatment of FCI; however, further study is required to better understand the risk of its use.

Iloprost for the treatment of frostbite: a scoping review.

We performed a scoping review to identify the extent of the literature describing the use of iloprost in the treatment of frostbite. Iloprost is a stable synthetic analog of prostaglandin I2. As a potent inhibitor of platelet aggregation and vasodilator, it has been used to address the post-rewarming reperfusion injury in frostbite. The search using iloprost and frostbite as key words and MeSH terms yielded 200 articles. We included in our review the literature examining iloprost for the treatment of frostbite in humans in the form of primary research, conference proceedings and abstracts. Twenty studies published from 1994 to 2022 were selected for analysis. The majority were retrospective case series consisting of a homogeneous population of mountain sport enthusiasts. A total of 254 patients and over 1000 frostbitten digits were included among the 20 studies. The larger case series demonstrated a decrease in amputation rates relative to untreated patients. Primary gaps in the literature include a paucity of randomised trials and relatively limited study populations to date. While the case evidence is promising, a multi-centre collaboration would be crucial to adequately power prospective randomised studies to definitively determine if iloprost has a role in the treatment of frostbite.

A new digital health tool for the telemonitoring of patients with scleroderma during iloprost administration: a feasibility and acceptability study.

OBJECTIVE: To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion. MATERIALS AND METHODS: In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device. RESULTS: Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working. CONCLUSIONS: Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Inhaled treprostinil vs iloprost: Comparison of adherence, persistence, and health care resource utilization in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with a substantial clinical and economic burden. Inhaled prostacyclins are a well-established part of pharmacotherapy for PAH. There are differences between inhaled therapies in the burden imposed by administration frequency. Simpler and less time-consuming inhaled PAH therapies may improve both adherence and persistence and potentially affect outcomes. OBJECTIVE: To compare real-world health care resource use, costs, and treatment adherence and persistence in patients with PAH who initiated inhaled treprostinil or iloprost. METHODS: Adult patients with 1 inpatient or 2 outpatient medical claims separated by at least 30 days with a diagnosis of PAH were identified using International Classification of Diseases, Ninth Revision or Tenth Revision, Clinical Modification codes with a pharmacy claim for inhaled treprostinil or iloprost. Patients were required to be continuously enrolled in the health plan for 6 months prior to and 12 months after the index date. A proportion of days covered of 0.8 or more was considered adherent; persistence was no gap in therapy for at least 60 days. All-cause health care resource utilization and all-cause costs were assessed. RESULTS: 405 and 62 patients were included in the inhaled treprostinil and iloprost cohorts, respectively. Adherence (50.9% and 22.6%; P < 0.0001) and persistence (6 months, 65.2% vs 35.5%; 12 months, 46.7% vs 16.1%; log-rank P < 0.001) were significantly better with inhaled treprostinil. Post-index allcause inpatient admissions (39.3% vs 54.8%; P = 0.02) and post-index emergency department (ED) utilization (36.3% vs 50.0%; P = 0.04) were lower with inhaled treprostinil. Among patients who were persistent with therapy through 12 months, there was no significant difference between groups in mean (SD) all-cause total costs ($266,462 [137,324] vs $262,826 [112,452] for inhaled treprostinil vs iloprost, respectively; P = 0.98). CONCLUSIONS: The results suggest that inhaled treprostinil is less burdensome, is associated with greater adherence and persistence, and may reduce all-cause hospitalizations and ED visits. DISCLOSURES: This study was funded by the United Therapeutics Corporation to obtain data for this analysis and compose the manuscript. Dr Burger has served as clinical investigator in multicenter interventional trials sponsored by United Therapeutics but did not receive any direct compensation. Drs Wu and Morland and Mr Classi are employees of United Therapeutics Corporation and own stock/shares in the company.

Kinetics of response to iloprost evaluated by laser speckle contrast analysis in systemic sclerosis.

OBJECTIVE: Iloprost (ILO) is recommended for the treatment of systemic sclerosis (SSc) microangiopathy, but there is no common consensus on its optimal dosage. The aim of this study is to evaluate the kinetics of response to ILO administered in a daily outpatient scheme in SSc subjects using laser speckle contrast analysis (LASCA). METHOD: Adult SSc patients in stable therapy with ILO administered for 6 h for 2 consecutive days every 4 weeks were enrolled. Peripheral finger perfusion was assessed by LASCA. Each patient underwent five LASCA evaluations: before and after each day of ILO (D1pre, D1post, D2pre, and D2post) and after 4 weeks (D30). RESULTS: Twenty-seven SSc patients (77.8% female, mean age 61.5 years) were enrolled. LASCA showed an increase in perfusion at the end of each ILO course, but on the second day (both D1pre vs D2pre and D2pre vs D2post) the increase was no longer significant in half of the fingers. Moreover, compared to D1post, at the beginning of the second ILO day most of the fingers had already shown a significant reduction in perfusion. After 1 month, there were no statistically significant differences between the perfusion values of D1pre and D30. CONCLUSION: This LASCA study highlights the transience of the vasoactive effect of ILO, with a perfusion benefit that is completely lost after 1 month. The brevity of the perfusion effect of ILO and the use of LASCA are elements to consider in the design of future SSc trials to determine the optimal ILO dosage.

Comparison of various treatment modalities for the management of bone marrow edema syndrome/transient osteoporosis in men and non-pregnant women: a systematic review.

Transient osteoporosis (TO) or bone marrow edema syndrome (BMES) is a self-limited clinical condition, which affects middle-aged men and women. It can be treated with miscellaneous conservative and surgical measures, which are analyzed in this systematic review. INTRODUCTION: BMES/TO is a transient clinical entity, which can be treated with various therapeutic modalities. The aim of our study was to assess the efficacy of different therapeutic options for the alleviation of pain and reduction of bone marrow edema (BME) in patients with BMES/TO, as well as to propose a therapeutic algorithm. METHODS: PubMed, Scopus, Cochrane, and Google Scholar were searched. Eligibility and extraction of studies were conducted by two authors. Methodological quality assessment was carried out with the modified Delphi technique, Methodological Index for Non-Randomized Studies (MINORS) criteria, and Cochrane Collaboration's risk of bias tool. Outcomes that were compared were time of pain resolution, VAS pain scores, and BME regression on magnetic resonance imaging (MRI). RESULTS: A total of 36 articles (880 patients) were included. Bisphosphonates had higher efficiency in less than 1-month outcomes on pain resolution compared with core decompression (CD), while iloprost was more efficient at 1-3 months compared with bisphosphonates and CD. At 3-6 months, all three of the aforementioned showed equal results on pain resolution, and at a period of 6-12 months, CD and extracorporeal shockwave therapy (ESWT) showed excellent results followed by bisphosphonates and the conservative group (CG) consisting of non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics and/or restricted weight bearing. On MRI at 1-3 months, bisphosphonates, iloprost, and CD had relatively the same outcomes on BME resolution, with the least promising being the CG. At 3-6 months, CD seemed to have achieved the best results on the resolution of BME, followed by ESWT, CG, and bisphosphonates group. At 6-12 months, ESWT had the best outcomes compared with the conservative, bisphosphonates, and iloprost groups. CONCLUSION: BMES/TO has been treated with many non-standardized measures due to the low number of highly reliable studies. Current literature shows promising results with regard to the reduction of the clinical course of BMES/TO, but further large multicenter randomized controlled trials, as well as standardized radiological and clinical scores, are warranted to acquire evidence-based recommendations on the therapeutic algorithm.

Protocol for intranasal chemoprevention delivery in a urethane mouse lung cancer model.

Mouse iloprost lung cancer chemoprevention studies typically use oral delivery. Here, we present a protocol for intranasal iloprost delivery within a urethane lung adenocarcinoma mouse model. We detail steps for intraperitoneal urethane injection in mice, followed by nine-week monitoring, intranasal iloprost treatment, and lungs harvesting for analysis. This iloprost delivery approach parallels an ongoing phase II clinical trial of inhaled iloprost for lung cancer chemoprevention. This protocol diversifies options for chemoprevention studies and offers a relevant and translatable model. For complete details on the use and execution of this protocol, please refer to Sompel et al. (2022).

The Prostacyclin Analogue Iloprost Modulates CXCL10 in Systemic Sclerosis.

The prostacyclin analogue iloprost is used to treat vascular alterations and digital ulcers, the early derangements manifesting in systemic sclerosis (SSc), an autoimmune disease leading to skin and organ fibrosis. Bioindicator(s) of SSc onset and progress are still lacking and the therapeutic approach remains a challenge. The T helper 1 (Th1) chemokine interferon (IFN)γ-induced protein 10 (IP-10/CXCL10) associates with disease progression and worse prognosis. Endothelial cells and fibroblasts, under Th1-dominance, release CXCL10, further enhancing SSc's detrimental status. We analyzed the effect of iloprost on CXCL10 in endothelial cells, dermal fibroblasts, and in the serum of SSc patients. Human endothelial cells and dermal fibroblasts activated with IFNγ/Tumor Necrosis Factor (TNF)α, with/without iloprost, were investigated for CXCL10 secretion/expression and for intracellular signaling cascade underlying chemokine release (Signal Transducer and Activator of Transcription 1, STAT1; Nuclear Factor kappa-light-chain-enhancer of activated B cells, NF-kB; c-Jun NH2-terminal kinase, JNK: Phosphatidyl-Inositol 3-kinase (PI3K)/protein kinase B, AKT; Extracellular signal-Regulated Kinase 1/2, ERK1/2). CXCL10 was quantified in sera from 25 patients taking iloprost, satisfying the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria for SSc, and in sera from 20 SSc sex/age-matched subjects without therapy, previously collected. In human endothelial cells and fibroblasts, iloprost targeted CXCL10, almost preventing IFNγ/TNFα-dependent cascade activation in endothelial cells. In SSc subjects taking iloprost, serum CXCL10 was lower. These in vitro and in vivo data suggest a potential role of iloprost to limit CXCL10 at local vascular/dermal and systemic levels in SSc and warrant further translational research aimed to ameliorate SSc understanding/management.

The Efficacy of Conservative Treatment of Bone Marrow Edema Syndrome: A Scoping Review of the Last Ten Years of Literature.

PURPOSE: The purpose of this review was to conduct a literature search assessing the efficacy of various conservative treatments of BMES. METHODS: According to the PRISMA guidelines, a literature search was conducted in April 2021 in MEDLINE database via PubMed and Embase to identify original articles describing the results of conservative treatments for BMES of hip and knee published in the last ten years. For each study, information regarding study characteristics, description of the treatment, patient's demographic and clinical data, length of follow-up, clinical outcome measure, disability, adverse events, classification, and extent and of edema on MRI, were extracted. RESULTS: A total of 12 studies were identified. Two studies described treatment with iloprost, three with hyperbaric oxygen (HBO), two with bisphosphonates, five with extracorporeal shockwave therapy (ESWT). The total number of patients was 351: 34 treated with iloprost, 64 with hyperbaric oxygen, 37 with bisphosphonates, 216 with ESWT. In ESWT studies, treatment with a higher flux density and a higher number of therapy sessions lead to better clinical and radiological scores. In iloprost studies, a more remarkable improvement in the VAS scale was observed in the study on hip patients. CONCLUSIONS: The treatment of idiopathic bone marrow edema is currently not standardized, making it difficult to find data that can be compared in a highly reliable way. The studies available in the literature show promising results as for the possibility to cure bone marrow edema efficiently. Standardized radiological scores for evaluating bone marrow edema area are needed in future studies.

Early Use of Iloprost in Nonfreezing Cold Injury.

Nonfreezing cold injury (NFCI) is caused by prolonged exposure to cold, usually wet conditions and represents a separate pathological entity from frostbite. The pathophysiology of NFCI is characterized by vasoconstriction and microcirculatory disturbance. Iloprost, a synthetic prostaglandin analogue with vasodilatory properties is a recognized adjuvant treatment in frostbite; however, its role in NFCI is unclear. We present a case of a 29-y-old man with severe NFCI to both forefeet after prolonged immersion in cold seawater. Initial treatment with passive rewarming, analgesia and aspirin was initiated. Infusion of iloprost was used within 24 h from presentation and was well tolerated. This resulted in reduced tissue loss compared to the apparent tissue damage documented during the initial assessment. Delayed surgical intervention allowed minor debridement and minor toe amputations, maintaining the patient's ability to ambulate. This case demonstrates the safe use of iloprost in acute NFCI and highlights the importance of delayed surgical intervention in patients presenting with severe NFCI.

Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study.

PURPOSE: We assessed the effectiveness and safety of a 5-day intravenous prostaglandin (iloprost) protocol at reducing digital amputation for patients with severe frostbite injuries at urban emergency departments. METHODS: This retrospective study examines consecutive patients who presented to Calgary emergency departments from April 2017 to April 2020 with Grade 2-4 frostbite injuries. Patients from February 2019 onward were managed using a 5-day iloprost infusion protocol, whereas patients prior to this time were managed with standard care (local best practice without iloprost as a therapeutic option). The primary effectiveness outcome was rate of affected digits amputated, stratified by frostbite severity. The secondary safety outcome was the incidence of serious adverse events associated with iloprost (allergic reactions or symptomatic hypotension requiring treatment or discontinuation of the infusion). RESULTS: 90 patients were included, 26 were treated with iloprost, compared to 64 patients who received usual care. Both the treatment and usual care groups experienced substantial rates of homelessness and substance use. No digital amputations were required for patients with Grade 2 injuries in either group, but significantly lower digital amputation rates were observed for patients with more severe frostbite injuries treated with iloprost versus usual care: Grade 3 (18% vs 44%, p < 0.001), Grade 4 (46% vs 95%, p < 0.001). No serious adverse events were associated with iloprost. CONCLUSION: In this unselected socially complex urban population, administration of iloprost for patients with frostbite was shown to be safe and was associated with lower digital amputation rates, particularly for those with more severe injuries.

RéSUMé: OBJECTIF: Nous avons évalué l'efficacité et la sécurité d'un protocole de 5 jours de prostaglandine intraveineuse (iloprost) pour réduire l'amputation digitale chez les patients souffrant d'engelures graves dans les services d'urgence urbains. MéTHODES: Cette étude rétrospective examine des patients consécutifs qui se sont présentés aux services d'urgence de Calgary d'avril 2017 à avril 2020 avec des engelures de niveau 2 à 4. À compter de février 2019, les patients ont été traités au moyen d'un protocole de perfusion d'iloprost de 5 jours, tandis que les patients avant cette période ont été pris en charge avec des soins standard (meilleures pratiques locales sans iloprost comme option thérapeutique). Le principal résultat d'efficacité était le taux de doigts affectés amputés, stratifié selon la gravité des gelures. Le critère secondaire de sécurité était l'incidence des événements indésirables graves associés à l'iloprost (réactions allergiques ou hypotension symptomatique nécessitant un traitement ou l'arrêt de la perfusion). RéSULTATS: 90 patients ont été inclus, 26 ont été traités avec de l'iloprost, contre 64 patients qui ont reçu les soins habituels. Les groupes de traitement et de soins habituels ont tous deux connu des taux importants de sans-abrisme et de consommation de substances. Aucune amputation digitale n'a été nécessaire pour les patients présentant des lésions de grade 2 dans l'un ou l'autre groupe, mais des taux d'amputation digitale significativement plus faibles ont été observés pour les patients présentant des lésions de gelures plus sévères traités par iloprost par rapport aux soins habituels : Grade 3 (18 % contre 44 %, p < 0,001), Grade 4 (46 % contre 95 %, p < 0,001). Aucun événement indésirable grave n'a été associé à l'iloprost. CONCLUSION: Dans cette population urbaine non sélectionnée et socialement complexe, l'administration d'iloprost pour les patients souffrant d'engelures s'est avérée sûre et a été associée à des taux d'amputation digitale plus faibles, en particulier pour ceux présentant des blessures plus graves.