Does Ileus Represent the Forgotten End Organ Failure in Critical Illness?

PURPOSE OF REVIEW: This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome. RECENT FINDINGS: Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN).

Transitions of care from the womb to the world: Implementation of inpatient neonatal med rec.

BACKGROUND: Medication use during pregnancy is common. Safety of fetal medication exposures is an important consideration for pregnancy and for pharmacologic management and care of newborns. OBJECTIVES: The objective of this study was to describe the impact of implementing a neonatal medication reconciliation service at an acute-care hospital. PRACTICE DESCRIPTION: A neonatal medication reconciliation process was implemented at the University of New Mexico Hospital, a level 4 maternity center in a 500-bed academic medical center. Pharmacy personnel identified inpatient pregnant and postpartum patients who required medication reconciliation. In addition to performing maternal medication reconciliation, clinically significant medication exposures that occurred during pregnancy were recorded for neonates. PRACTICE INNOVATION: Our neonatal medication reconciliation process evaluated prenatal "medication use" via a maternal medication history. We considered our medication reconciliation to be occurring during a "transition" from in utero to being born, which, to the best of our knowledge, has not been commonly reported as a transition of care in which pharmacists may play a role. EVALUATION METHODS: We conducted a retrospective descriptive chart review of patients who had both maternal and neonatal medication reconciliation services performed. We collected demographics, comorbidities, medications, and clinically significant exposures from the medication reconciliation note. RESULTS: A total of 384 charts were included in the final analysis. Of these, 167 medication reconciliations (43.5%) identified at least one medication history problem and 97 medication histories (25.3%) identified at least one potentially clinically significant neonatal medication exposure. PRACTICE IMPLICATIONS: Although several limitations exist, a neonatal medication reconciliation process can be implemented in any inpatient setting with pharmacy staff available to perform and record reconciliation. CONCLUSION: Opportunities for pharmacist involvement in pregnancy, postpartum, and neonatal care are expected to increase. Further research is warranted to more clearly determine the maternal and neonatal benefits of this medication reconciliation process and to link fetal exposures to outcomes.

Analysis of prognostic germline polymorphisms in patients with advanced hepatocellular carcinoma.

Background: The prognosis of hepatocellular carcinoma (HCC) is influenced by both tumor and patient specific factors. Current therapies of advanced HCC target angiogenesis and immune evasion, however there are no clinically useful biomarkers to guide clinicians. Methods: Our aim in this retrospective cohort study was to validate single nucleotide polymorphisms (SNPs) prognostic of outcome in advanced HCC from the literature, and to analyze exploratory SNPs chosen from evaluation of the HCC tumor immune microenvironment. Using a database of patients with HCC treated with sorafenib, blood samples were genotyped, clinical variables were retrospectively collected, and SNPs were analyzed for association with progression-free survival (PFS) and overall survival (OS). A subsequent analysis was conducted to determine if identified SNPs were prognostic in trans arterial chemoembolization (TACE) treated patients. Results: Literature review identified 7 SNPs in vascular endothelial growth factor (VEGF), eNOS, angiopoietin 2 (ANGPT2) and vascular endothelial growth factor receptor 2 (VEGFR2), however none were externally validated in our dataset. Of the 35 exploratory immunomodulatory SNPs, the following were associated with PFS or OS: CCL2 C-C motif ligand 2 (CCL2) (rs1024611), interleukin-10 (IL-10) (rs1800896), cytotoxic T-lymphocyte antigen-4 (CTLA-4) (rs231775) and NFKB1 (rs28362491). Conclusions: SNPs identified by literature review to be prognostic in sorafenib treated patients with advanced HCC were not validated in our dataset. Our findings suggest potentially important prognostic implications of SNPs in VEGFR2, CCL2, IL-10, CTLA-4 and NFKB1 that deserve further study.

Nonatopic Eosinophilic Duodenitis in an Adult: A Case Report and Overview.

Eosinophilic duodenitis is an inflammation of the duodenum, characterized by an abundance of eosinophils, typically triggered by hypersensitivity reactions. Typically, recurrent abdominal pain with eosinophilic duodenitis is rare in individuals without a history of atopic conditions like asthma. Here, we present the case of a 62-year-old man who experienced recurrent upper abdominal pain for 12 months and unintended weight loss for the past six months. The patient reported no allergies to food, drugs, or the environment, and has no history of other atopic conditions. Esophagogastroduodenoscopy (EGD) with biopsy of the duodenum and stomach revealed 32 eosinophils per high-power field (HPF), which is mild. Skin prick testing yielded negative results. Following initial treatment with H2 inhibitors, proton pump inhibitors, and budesonide for a total of 12 weeks, the patient reported an improvement in symptoms and subsequent weight gain. This report emphasizes a rare case of eosinophilic duodenitis in a nonatopic individual with a successful treatment regimen. His quality of life improved with weight gain, resolved abdominal pain, and improved appetite. Although the patient's condition lasted about 12 months, our report showcased the importance of timely clinical diagnosis and appropriate combination therapy to alleviate progressive pain associated with eosinophilic duodenitis.

A Radiomics-Based Classifier for the Progression of Oropharyngeal Cancer Treated with Definitive Radiotherapy.

In this study, we investigated whether radiomics features from pre-treatment positron emission tomography (PET) images could be used to predict disease progression in patients with HPV-positive oropharyngeal cancer treated with definitive proton or x-ray radiotherapy. Machine learning models were built using a dataset from Mayo Clinic, Rochester, Minnesota (n = 72) and tested on a dataset from Mayo Clinic, Phoenix, Arizona (n = 22). A total of 71 clinical and radiomics features were considered. The Mann-Whitney U test was used to identify the top 2 clinical and top 20 radiomics features that were significantly different between progression and progression-free patients. Two dimensionality reduction methods were used to define two feature sets (manually filtered or machine-driven). A forward feature selection scheme was conducted on each feature set to build models of increased complexity (number of input features from 1 to 6) and evaluate model robustness and overfitting. The machine-driven features had superior performance and were less prone to overfitting compared to the manually filtered features. The four-variable Gaussian Naïve Bayes model using the 'Radiation Type' clinical feature and three machine-driven features achieved a training accuracy of 79% and testing accuracy of 77%. These results demonstrate that radiomics features can provide risk stratification beyond HPV-status to formulate individualized treatment and follow-up strategies.

Bouveret Syndrome: A Rare and Often Fatal Form of Gallstone Ileus.

Bouveret syndrome (BS) is a rare but serious complication of gallstone ileus that can cause gastric outlet obstruction secondary to a gallstone impacted in the pylorus or proximal duodenum. Gallstones pass from the gallbladder to the GI tract via a cholecystoenteric fistula that forms as a result of chronic inflammation and adhesions between the biliary system and GI tract. Although the case we are presenting is of a 53-year-old Hispanic male, females and the elderly are particularly at an increased risk of this condition. BS can present as typical mechanical obstruction symptoms that include nausea, vomiting, and diffuse abdominal pain. The vague symptoms patients present with makes the diagnosis difficult and often delayed, which can be fatal. In our case, the diagnosis of BS was supported by a CT with contrast, MRI, and an esophagogastroduodenoscopy (EGD) study. Our patient underwent an exploratory laparotomy after the diagnosis was made, and the stone was removed. Here, we aim to raise awareness of the importance of early recognition, and immediate action in establishing an early diagnosis of BS in patients presenting with nonspecific abdominal symptoms, which can prevent mortalities.

A Rare Finding of Gastric Pseudomelanosis in Chronic Kidney Disease: A Case Report.

Pseudomelanosis is a black-brown discoloration of the loose connective tissue layer of the intestinal mucosa, also known as the lamina propria. Although it is a benign condition and poses no real threat to the patient, it has been known to be associated with certain medication use in the colon, like anthraquinone laxatives, as well as various chronic illnesses in the duodenum and stomach, like iron deficiency anemia, end-stage kidney disease, hypertension, and diabetes mellitus. Only a handful of cases of gastric pseudomelanosis have been reported in the literature, often presenting to the physician as an elderly female with dark, tarry stools from excessive iron use. In this unusual case, a 75-year-old male came to the emergency room due to a concern about blackish stools in the toilet. After reviewing his past medical history, it was found that he takes iron tablets for anemia secondary to end-stage renal disease. While enteric iron was most likely the cause of the melena, an esophagogastroduodenoscopy (EGD) study was performed to rule out any proximal causes of gastrointestinal bleeding. Following the upper endoscopy, gastric pseudomelanosis was established.

Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

BACKGROUND: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. METHODS: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. RESULTS: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. CONCLUSIONS: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

Abdominal Migraines: A Rare Adulthood Manifestation of a Typical Childhood Disease.

Abdominal migraine (AM) is a common childhood disease that rarely presents in adulthood. While multiple diagnostic guidelines have been established, AM can generally be described as unprovoked episodes of acute central abdominal pain with migrainous features and periods of relief. AM is believed to be caused by a disturbance in the gut-brain axis. We are presenting a case of a 47-year-old Caucasian female with a six-month history of abdominal pain and vomiting. The episodes occurred one to two times per week, for 12-18 hours. These episodes were unprovoked and the patient felt normal in between episodes. Her past medical history is notable for hypertension and childhood migraines. Extensive imaging and laboratory workups were unremarkable. A trial of as-needed 50-milligram sumatriptan was started. The patient's symptoms were aided and became less frequent over the next three months. Although uncommon, this patient's case presents convincing evidence of AM. Cyclic vomiting syndrome (CVS), another disease of gut-brain access, was once thought to be a pediatric disease. However, further research showed relevant prevalence in the adult population. CVS has a similar mechanism and treatment plan to AM. It seems plausible that a closely related gut-brain axis disorder like AM could have more prevalence in the adult population. To better identify AM in adults, it is important that physicians inquire about a history of childhood migraines when faced with vague abdominal symptoms. Increased identification of AM will help guide treatment and improve patient outcomes.

Rotating Gantries Provide Individualized Beam Arrangements for Charged Particle Therapy.

PURPOSE: This study evaluates beam angles used to generate highly individualized proton therapy treatment plans for patients eligible for carbon ion radiotherapy (CIRT). METHODS AND MATERIALS: We retrospectively evaluated patients treated with pencil beam scanning intensity modulated proton therapy from 2015 to 2020 who had indications for CIRT. Patients were treated with a 190° rotating gantry with a robotic patient positioning system. Treatment plans were individualized to provide maximal prescription dose delivery to the tumor target volume while sparing organs at risk. The utilized beam angles were grouped, and anatomic sites with at least 10 different beam angles were sorted into histograms. RESULTS: A total of 467 patients with 484 plans and 1196 unique beam angles were evaluated and characterized by anatomic treatment site and the number of beam angles utilized. The most common beam angles used were 0° and 180°. A wide range of beam angles were used in treating almost all anatomic sites. Only esophageal cancers had a predominantly unimodal grouping of beam angles. Pancreas cancers showed a modest grouping of beam angles. CONCLUSIONS: The wide distribution of beam angles used to treat CIRT-eligible patients suggests that a rotating gantry is optimal to provide highly individualized beam arrangements.

Portal Hypertension Due to Hepatoportal Sclerosis in an HIV-Positive Patient Secondary to Didanosine Use.

Noncirrhotic portal hypertension (NCPH) has recently been found in human immunodeficiency virus (HIV)-infected patients taking didanosine. Here, we describe an HIV-infected patient with portal hypertension due to hepatoportal sclerosis who presented with hematemesis at the emergency department (ED). CT angiography of the abdomen and pelvis with and without contrast revealed a diminutive portal vein with corresponding massive lower esophageal varices and superior mesenteric vein to the right gonadal vein varices. Esophagogastroduodenoscopy (EGD) revealed grade II varices were found in the lower third of the esophagus, for which the patient's symptoms improved with emergency endoscopic band ligation, octreotide and didanosine discontinuation. Our case demonstrates a rare complication that can occur with continued didanosine use in an HIV-positive patient. We highlight the need for a standard diagnostic upper gastrointestinal endoscopy to screen for portal hypertension and high-risk esophageal varices in patients with long-term didanosine use as seen in our patient.

Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data.

The incidence and biochemical consequences of rare tumor subtypes are often hard to study. Fibrolamellar liver cancer (FLC) is a rare malignancy affecting adolescents and young adults. To better characterize the incidence and biochemical consequences of this disease, we combined a comprehensive analysis of the electronic medical record and national payer data and found that FLC incidence is likely five to eight times higher than previous estimates. By employing unsupervised learning on clinical laboratory data from patients with hyperammonemia, we find that FLC-associated hyperammonemia mirrors metabolic dysregulation in urea cycle disorders. Our findings demonstrate that advanced computational analysis of rich clinical datasets can provide key clinical and biochemical insights into rare cancers.

Cecal Endometriosis Presenting as Hematochezia in a Postmenopausal Female.

Our report highlights the diagnosis of cecal endometriosis as a unique cause of hematochezia in a postmenopausal female. Cecal endometriosis manifesting as intermittent hematochezia and abdominal pain is uncommon but requires prompt clinical diagnosis and management. We report a case of cecal endometriosis causing hematochezia and subsequent syncope, which prompted the patient's admission to the emergency department. In our patient, a diagnosis of cecal endometriosis was made after a colonoscopy, with multiple biopsies confirming the presence of endometrial tissue embedded in the cecum. We aim to bring awareness of cecal endometriosis presenting as hematochezia in a postmenopausal woman with a history of abdominal pain. This case highlights intestinal endometriosis as a differential diagnosis to be considered in women, regardless of age, with intermittent hematochezia and abdominal pain.

Symptoms of Chronic Dysphagia Secondary to Multiple Cervical Inlet Patches and Esophageal Stricture.

Ectopic gastric mucosa can be present throughout the gastrointestinal tract; however, when located within the upper esophagus, it is termed an esophageal inlet patch. To the best of our knowledge, most esophageal inlet patches occur as a single area of gastric mucosa. Here, we present a 44-year-old female who suffered from symptoms of chronic dysphagia and globus sensation for two years due to multiple inlet patches located in the cervical area of the upper esophagus with an associated cervical esophageal stricture. The patient underwent esophageal dilation and proton pump inhibitor therapy, resulting in a resolution of her symptoms. Our case demonstrates the appropriate clinical management of patients suffering from symptoms of chronic dysphagia due to multiple esophageal inlet patches. We recommend routine examination of the cervical esophagus in developing a differential diagnosis of inlet patch, especially in patients with chronic upper dysphagia.

Nonatopic Eosinophilic Esophagitis in an Adult.

Eosinophilic esophagitis (EoE) is an inflammatory condition limited to the esophagus, predominantly consisting of eosinophils, and triggered by hypersensitivity reactions. Recurrent dysphagia secondary to EoE is uncommon in patients with no history of asthma and/or atopic conditions. We are presenting a case of a 48-year-old male suffering from dysphagia for 10 years that worsened over a six-month period. The patient reported no known food and drug allergies, asthma, and other atopic conditions. On esophagogastroduodenoscopy (EGD), the patient fulfilled all five endoscopic reference score (EREFS) criteria, granting a final diagnosis of eosinophilic esophagitis with a score of 6. Biopsy confirmed eosinophilic esophagitis, revealing 20 eosinophils/high-power fields. Skin prick testing was negative. His symptoms had improved at the office follow-up after three weeks after esophageal dilation and proton pump inhibitor (PPI) but did not completely resolve. The patient was then started on fluticasone 440 mcg two times a day. After eight weeks, the patient was symptom-free by taking dual therapy of PPI and fluticasone. The patient was advised to continue taking the daily PPI and then a six-week course of fluticasone if he experienced an exacerbation in his symptoms. In this report, symptom improvement with esophageal dilation, PPI, and fluticasone suggested a successful treatment regimen for EoE in the setting of no known atopy in our patient. Our case highlights EoE in an adult with no known asthma and allergies. The report identifies the importance of a prompt clinical diagnosis and appropriate combination treatment due to the progressive pain and its worsening associated with eosinophilic esophagitis.

Nuclear Fragmentation Imaging for Carbon-Ion Radiation Therapy Monitoring: an In Silico Study.

Purpose: This article presents an in vivo imaging technique based on nuclear fragmentation of carbon ions in irradiated tissues for potential real-time monitoring of carbon-ion radiation therapy (CIRT) treatment delivery and quality assurance purposes in clinical settings. Materials and Methods: A proof-of-concept imaging and monitoring system (IMS) was devised to implement the technique. Monte Carlo simulations were performed for a prospective pencil-beam scanning CIRT nozzle. The development IMS benchmark considered a 5×5-cm2 pixelated charged-particle detector stack positioned downstream from a target phantom and list-mode data acquisition. The abundance and production origins, that is, vertices, of the detected fragments were studied. Fragment trajectories were approximated by straight lines and a beam back-projection algorithm was built to reconstruct the vertices. The spatial distribution of the vertices was then used to determine plan relevant markers. Results: The IMS technique was applied for a simulated CIRT case, a primary brain tumor. Four treatment plan monitoring markers were conclusively recovered: a depth dose distribution correlated profile, ion beam range, treatment target boundaries, and the beam spot position. Promising millimeter-scale (3-mm, ≤10% uncertainty) beam range and submillimeter (≤0.6-mm precision for shifts <3 cm) beam spot position verification accuracies were obtained for typical therapeutic energies between 150 and 290 MeV/u. Conclusions: This work demonstrated a viable online monitoring technique for CIRT treatment delivery. The method's strong advantage is that it requires few signal inputs (position and timing), which can be simultaneously acquired with readily available technology. Future investigations will probe the technique's applicability to motion-sensitive organ sites and patient tissue heterogeneities. In-beam measurements with candidate detector-acquisition systems are ultimately essential to validate the IMS benchmark performance and subsequent deployment in the clinic.

Phase II clinical trial of cabozantinib for the treatment of recurrent hepatocellular carcinoma after liver transplantation.

Recurrent hepatocellular carcinoma (HCC) develops in 15-20% of liver transplant recipients, and it tends to be more aggressive due to underlying immunosuppression. The multikinase inhibitor cabozantinib has been shown to be effective for the treatment of advanced HCC. However, there is no study evaluating this medication in patients with recurrent HCC. Adult patients with measurable biopsy-proven recurrent HCC are eligible for enrollment provided they are not amenable to curative treatments and no prior treatment with cabozantinib. In this study, 60 mg once daily cabozantinib will be administered orally. Participants will receive study treatment as long as they continue to experience clinical benefit or until there is unacceptable toxicity. Tumor measurements will be repeated every 8 weeks to evaluate response. The primary end point of this study will be the disease control rate at 4 months after treatment. The secondary end points will be overall survival, progression-free survival and safety profile of cabozantinib. Furthermore, potential biomarkers will be evaluated to identify their role in tumor progression. The total duration of this trial is expected to be 3 years. We anticipate that this trial will show the effectiveness and safety of cabozantinib in the treatment of post-liver transplant recurrent HCC. Cabozantinib is expected to be an effective treatment due to its activity against many protein kinases, including MET and AXL which are not inhibited by sorafenib.

Liver cancer is the sixth most diagnosed cancer worldwide with few available curative treatments. Liver transplantation (LT) is considered as one of the treatments for liver cancer especially in earlier stages of cancer. However, after LT, cancer develops again in 15­20% of the patients who undergo transplant for liver cancer. Compared with liver cancer in the nontransplant population, recurrent cancer grows faster and spreads in the body very quickly. Therefore, unfortunately, to date there are limited treatment options for these patients without significant effect on their survival. In this study, we aim to evaluate the effect of a new medication called cabozantinib on patients who develop recurrent liver cancer after their LT. Cabozantinib has been already tested in patients with liver cancer and was shown to be effective and safe in nontransplant patients. However, this is the first study to evaluate the effect of cabozantinib in liver transplant recipients with recurrent liver cancer. Clinical Trial Registration: NCT04204850 (ClinicalTrials.gov).

Severity of neonatal opioid withdrawal syndrome with prenatal exposure to serotonin reuptake inhibitors.

OBJECTIVE: To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). METHODS: A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. RESULTS: Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). CONCLUSIONS: Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. IMPACT: A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.

Treatment Patterns and Outcomes of Patients With Advanced Pleural Mesothelioma at an Academic Referral Centre.

BACKGROUND: Overall survival (OS) for malignant pleural mesothelioma (MPM) in vulnerable subgroups remains poorly understood with scarce data available to guide treatment decisions. The study describes real-world detailed treatment patterns and outcomes of patients with advanced MPM overall and specifically in elderly and poor performance status (PS) patients. METHODS: Retrospective chart review was performed for all patients with histologically confirmed MPM seen at University Health Network/Princess Margaret Cancer Centre (UHN-PM). RESULTS: A total of 667 patients with MPM were identified and 304 advanced-disease MPM (aMPM) patients had continuing care at UHN-PM (UP-cohort). In the UP-cohort, 77% of patients received ≥ one line of systemic treatment. Systemic therapy trial participation was 39%. Patients not treated with systemic therapy (29%) were more likely to be ≥ 75 years and PS ≥ 2. Median OS was 15.3 months (95%CI 13.6-18.3), with longer survival in treated vs. untreated patients (17.4 vs. 10.6 months; P = .01). Longer survival with systemic treatment was seen in patients ≥75 years (12.7 vs. 6.6 months) and patients with poor PS (9.1 vs. 5.9 months). Median progression-free-survival (PFS) and OS for patients treated with second-line therapy was poor (3.0 and 8.9 months, respectively). DISCUSSION: In our real-world analysis of patients with aMPM treated at an academic referral centre, systemic treatment was given to the majority of patients and benefit was seen even in the elderly and poor PS patients frequently underrepresented in clinical trials. Trial participation was potentially facilitated by the formation of a dedicated multidisciplinary MPM clinic.