Transient pulmonary and gastric bleeding after iopamidol administration in a patient with marginal zone lymphoma: a case report.

BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication. CASE PRESENTATION: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding. CONCLUSION: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.

Pulmonary haemorrhage and extensive arterial thrombosis with anabolic steroid abuse.

Anabolic-androgenic steroids (AASs) are commonly implicated in thromboembolic events but rarely cause diffuse alveolar haemorrhage. We report the case of a Caucasian man in his late 40s who was consuming supratherapeutic doses of AAS and presented with shortness of breath and haemoptysis. Chest imaging showed bilateral patchy infiltrates in the lungs with diffuse blood throughout the airways on bronchoscopy. Extensive infectious and autoimmune workup were unremarkable. The patient then developed right foot ischaemia and was found to have extensive aortic and bilateral lower extremity arterial thrombosis. Anticoagulation was attempted despite haemoptysis. Thrombectomy procedures were unsuccessful and the patient eventually developed worsening rhabdomyolysis requiring intubation and bilateral amputation. His clinical condition continued to worsen and he passed away 10 days after admission. This case highlights the rare synchronous occurrence of two life-threatening complications secondary to anabolic steroid abuse which can pose a significant diagnostic and therapeutic challenge for clinicians.

Lung squamous cell carcinoma with hemoptysis after vaccination with tozinameran (BNT162b2, Pfizer-BioNTech).

A 66-year-old man with squamous cell carcinoma had been receiving chemoradiation therapy after stereotactic radiotherapy for brain metastases. Atezolizumab was initiated as second-line therapy, after which the patient became progression- and recurrence-free. Four days after his second dose of tozinameran (BNT162b2, Pfizer-BioNTech), the patient developed persistent hemoptysis. The patient had no thrombocytopenia or coagulation abnormalities. Bronchoscopy revealed active bleeding from the left lingual tracheal branch. The patient was intubated and admitted to the intensive care unit because of increased bleeding. Subsequently, left bronchial artery embolization was performed using a Serescue. Hemostasis was achieved after the procedure, and the patient was discharged 7 days after the onset of hemoptysis. Vaccination against coronavirus disease has been reported to be associated with thrombosis and cerebral hemorrhage, and the hemoptysis in this case was suspected to be induced by vaccination. In summary, the benefits of vaccination exceeded the risks of adverse events in a patient with cancer. However, in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, patients should be carefully monitored for hemorrhagic events after vaccination.

Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS: The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 . FINDINGS: Between Sept 4, 2012, and Aug 23, 2018, 256 patients were randomised. Final follow-up was on Feb 25, 2019. We excluded three patients who revoked consent and one ineligible participant who received no intervention. Of 252 patients included in data analysis, the mean age was 58 years (SD 15), 157 (62%) were men, and 118 (47%) had ARDS. 128 (51%) patients were assigned to the heparin group and 124 (49%) to the placebo group, all of whom received their assigned intervention. Survivors in the heparin group (n=97) had similar SF-36 Physical Function Scores at day 60 compared to the placebo group (n=94; mean 53·6 [SD 31·6] vs 48·7 [35·7]; difference 4·9 [95% CI -4·8 to 14·5]; p=0·32). Compared with the placebo group, the heparin group had fewer cases of ARDS develop to day 5 among the at-risk patients (nine [15%] of 62 patients vs 21 [30%] of 71 patients; hazard ratio 0·46 [95% CI 0·22 to 0·98]; p=0·0431), less deterioration of the MLIS to day 5 (difference -0·14 [-0·26 to -0·02]; p=0·0215), similar day 60 mortality (23 [18%] of 127 patients vs 18 [15%] of 123 patients; odds ratio [OR] 1·29 [95% CI 0·66 to 2·53]; p=0·46), and more day 60 survivors at home (86 [87%] of 99 patients vs 73 [73%] of 100 patients; OR 2·45 [1·18 to 5·08]; p=0·0165). A similar number of serious adverse events occurred in each group (seven [5%] of 128 patients in the heparin group vs three [2%] of 124 patients in the placebo group; OR 2·33 [0·59 to 9·24]; p=0·23), which were a transient increase in airway pressure during nebulisation (n=3 in the heparin group), major non-pulmonary bleeding (n=2 in each group), haemoptysis (n=1 in the heparin group), tracheotomy site bleeding (n=1 in the heparin group), and hypoxaemia during nebulisation (n=1 in the placebo group). INTERPRETATION: In patients with or at risk of ARDS, nebulised heparin did not improve self-reported performance of daily physical activities, but was well tolerated and exploratory outcomes suggest less progression of lung injury and earlier return home. Further research is justified to establish if nebulised heparin accelerates recovery in those who have or are at risk of ARDS. FUNDING: Rowe Family Foundation, TR and RB Ditchfield Medical Research Endowment Fund, Patricia Madigan Charitable Trust, and The J and R McGauran Trust Fund.

Value of Coronary Artery Calcium Scanning in Association With the Net Benefit of Aspirin in Primary Prevention of Atherosclerotic Cardiovascular Disease.

Importance: Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear. Objective: To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds. Design, Setting, and Participants: Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020. Exposures: Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher. Main Outcomes and Measures: Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis-derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds. Results: A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk. Conclusions and Relevance: Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.

Diffuse alveolar hemorrhage secondary to plastic fume exposure: A case report.

A 31-year non-smoker man, working in plastic making industry for 12 years presented with cough and streaking hemoptysis for 2 days. Computed tomography (CT) of chest showed patchy ground glass opacities with interlobular septal thickening in bilateral lung parenchyma. Fiber optic bronchoscopy (FOB) was done. Sequential lavage was taken which showed progressively increasing hemorrhagic fluid. His diffusion capacity for carbon monoxide (DLCO) was 38.08 mL/mmHg/Mi (126%) predicted on day 2 of admission, 32.36 ml/mmHg/Mi (106%) predicted on discharge and 39.63 mL/mmHg/Mi (130%) predicted on going back to work. He was diagnosed with plastic fume exposure related pulmonary alveolar hemorrhage.

Cavitation and fatal hemoptysis after immunotherapy for advanced lung adenocarcinoma: A case report.

Immune checkpoint inhibitor (ICI)-related massive hemoptysis with cavitation has rarely been identified. Here, we report a case of advanced lung adenocarcinoma with lethal bleeding after eight cycles of pembrolizumab. A 55-year-old male was diagnosed with stage IV non-small cell lung cancer (NSCLC). Following confirmation of high programmed death-ligand 1 (PD-L1) expression of 60% cancer cells, he subsequently received pembrolizumab monotherapy. His symptoms and chest images significantly improved after four cycles of therapy. However, after eight cycles of immunotherapy, he presented with recurrence of bloody sputum and shortness of breath. Pembrolizumab was discontinued and a diagnosis of checkpoint inhibitor-associated pneumonitis (CIP) was made. When the CIP was absorbed after glucocorticoid therapy, the patient died of sudden massive hemoptysis with cavitation in the lesion. KEY POINTS: Although checkpoint inhibitor associated pneumonitis was the leading cause of ICI-related death, clinicians should be alerted to the finding that more attention should be given to hemoptysis attributed to ICI therapy in advanced lung cancer.

A case of lung injury resembling diffuse pulmonary hemorrhage after the first administration of alemtuzumab in a patient with multiple sclerosis. Role of the HRCT.

Diffuse alveolar hemorrhage (DAH) is an acute often life-threatening condition characterized by a variable combination of hemoptysis, dyspnoea, diffuse and bilateral ground glass pulmonary opacities, anemia and hypoxemia, that can be induced by different causes, including several drugs. We report here the case of a 25-year-old woman who has been admitted to our pulmonary clinic for the onset of chest pain, cough and haemoptysis, started one week after her first treatment with alemtuzumab for multiple sclerosis. Computed tomography (CT) scan of the chest at the admission showed diffuse and bilateral ground glass pulmonary opacities. Her symptoms resolved completely without any treatment, after the interruption of alemtuzumab, and CT scan of the chest performed one month later showed total disappearance of the pulmonary opacities.

Sevoflurane induced diffuse alveolar haemorrhage in a young patient after orthopedic surgery: A case report.

We present a very rare case of Sevoflurane Induced Diffuse Alveolar Haemorrhage in a young male patient with a closed tibial fracture after direct trauma to the right cruris. The patient was operated for tibial fracture, but diffuse alveolar haemorrhage developed after sevoflurane inhalation in the postoperative period following general anesthesia. Diffuse alveolar haemorrhage (DAH) is associated with inhalation injury from halogenated gases and reported as a unique entity in the literature that practicing clinicians should be aware of and consider in post-operative cases of acute respiratory distress. As DAH usually presents with symptoms the presence of hemoptysis, anemia, dyspnoea and radiological alveolar infiltrates, rapid detection of the aetiology and initiation of cause-directed treatment are of great importance on survival.

Unusual presentation of haemoptysis following accidental inhalation of the 'superwarfarin' rodenticide brodifacoum.

Haemoptysis is a worrying symptom for patients and can represent a diagnostic challenge for clinicians. We present the case of a 56-year-old woman who presented to the emergency department with acute haemoptysis and associated sudden-onset dyspnoea. The patient remained haemodynamically stable and there was no demonstrable drop in haemoglobin concentration. Following rigorous investigations, on further questioning, the patient recalled inadvertent inhalation of the rodenticide brodifacoum. This exposure was deemed to represent the cause of their acute haemoptysis, which subsequently fully resolved without intervention.

[A rare and severe complication related to acenocoumarol therapy: intra-alveolar bleeding]. / Une complication rare et grave du traitement par l'acénocoumarol: l'hémorragie intra-alvéolaire.

Intra-alveolar bleeding is a rare and severe medical emergency due to numerous causes. We report the clinical case of a patient who could contribute to extend the literature on this subject. The study included a 62-year old man, with a history of a trial fibrillation, under anti-vitamins K antagonist admitted with dyspnoea of sudden onset associated with haemoptysis and practising self-medication using non-steroidal anti-inflammatory drugs. X-rays and chest scan showed diffuse bilateral alveolar opacities. Haemostatic screening tests on admission showed non-coagulable INR. The diagnosis of intra-alveolar bleeding was clinically and radiologically suspected and then confirmed by bronchial endoscopy with broncho-alveolar lavage (BAL) which detected uniformly hemorrhagic liquid. Previous studies of similar complications occurring after anti-vitamins K antagonists assumption are rare. In conclusion, it seems very important to emphasize the interest of strict and optimal clinico-biological monitoring of patients treated in anti-vitamins K antagonists to avoid an overdose which could contribute to a life-threatening severe haemorrhagic event.

Early fatal hemoptysis after first-dose, first-line pembrolizumab in a central lung cancer: did tumor shrinkage matter?

A patient diagnosed with centrally located advanced lung adenocarcinoma with signs of large vessels infiltration, strongly expressing PD-L1, was candidate to first-line pembrolizumab. He had not complained of any bleeding manifestation before immunotherapy. 5 days after the first dose of pembrolizumab, the patient experienced massive, fatal hemoptysis. Given the central localization of the tumor and the strong PD-L1 expression, a contribution of rapid disease shrinkage is envisaged in determining the fatal hemorrhagic event. An attentive clinical attitude should be dedicated in centrally located and vessel-infiltrating tumors strongly expressing PD-L1 and candidate to anti-PD-1/PD-L1 agents.

Role of Hypertension and Other Clinical Variables in Prognostication of Patients Presenting to the Emergency Department With Major Bleeding Events.

BACKGROUND: Clinical variables including hypertension could be linked with major bleeding events and death beyond vitamin K antagonist (warfarin) or direct oral anti-coagulants (DOACs) treatment strategy. METHODS: Subgroup analysis of major bleeding (primary endpoint) associated with clinical variables, site of bleeding, ongoing antithrombotics, reversal treatment or blood transfusion, outcomes (secondary endpoints) was performed in patients with bleeding events submitted to hard 5:1 propensity-score matching for hypertension. RESULTS: Enrolled patients were 2,792 (mean age, 65.6 ± 19.9 years) during 2-year survey including 166,000 visits, of 200,000 inhabitants catchment area; 8,239 patients received warfarin and 3,797 DOACs. Hypertension account for 1,077 (39%) patients; major bleeding for 474 (17%); death for 29 (1%), and 72 (3%) on 1-month and 1-year, respectively. Hypertension, age, glucose, cancer, ischemic vascular disease, and CHA2D2VASc score were more likely to link with major bleeding. On multivariate analysis, only age (odds ratio [OR], 1.02; P < 0.001), CHA2DS2VASc score ≥ 2 (OR, 2.14; P = 0.001), and glucose (OR, 1.01; P = 0.005) were predictors of major bleeding. Kaplan-Meier analysis demonstrated patients with hypertension as compared with patients without showed 60% versus 20% death on 1-month (P < 0.001). Warfarin compared with DOACs was more likely to present with major bleeding (0.7% versus 0.2%; OR, 2.8; P = 0.005). Receiver operator characteristics analysis showed high value (0.61) of age and glucose over creatinine and systolic arterial pressure (P = NS). CONCLUSIONS: Four in 10 patients with major bleeding showed hypertension; of these 8 in 10 will die within 1 month. Warfarin compared with DOACs was more likely to present with major bleeding.