Alveolar Hemorrhage Research Articles

Increased Mortality Risk at Septic Condition in Inflammatory Skin Disorders and the Effect of High-Fat Diet Consumption.

In recent years, attention has increasingly focused on various infectious diseases. Although some fatalities are directly attributed to the causative virus, many result from complications and reactive inflammation. Patients with comorbidities are at a higher risk of mortality. Refractory skin conditions such as atopic dermatitis, psoriasis, and epidermolysis bullosa, known for an elevated risk of sepsis, partly owe this to compromised surface barrier function. However, the detailed mechanisms underlying this phenomenon remain elusive. Conversely, although the detrimental effects of a high-fat diet on health, including the onset of metabolic syndrome, are widely recognized, the association between diet and susceptibility to sepsis has not been extensively explored. In this study, we examined the potential causes and pathogenesis of increased sepsis susceptibility in inflammatory skin diseases using a mouse dermatitis model: keratin 14-driven caspase-1 is overexpressed (KCASP1Tg) in mice on a high-fat diet. Our findings reveal that heightened mortality in the dermatitis mouse model is caused by the inflamed immune system due to the chronic inflammatory state of the local skin, and administration of LPS causes a rapid increase in inflammatory cytokine levels in the spleen. Intake of a high-fat diet exacerbates these cytokine levels. Interestingly, we also observed a reduced expression of Toll-like receptor 4 (TLR4) in monocytes from KCASP1Tg mice, potentially predisposing these animals to heightened infection risks and associated complications. Histological analysis showed a clear decrease in T and B cells in the spleen of KCASP1Tg mice fed a high-fat diet. Thickening of the alveolar wall, inflammatory cell infiltration, and alveolar hemorrhage were more prominent in the lungs of KCASP1Tg and KCASP1Tg with fat mice. We postulate that the chronic, non-infectious inflammation induces a negative feedback loop within the inflammatory cascade, and the suppressed expression of TLR4 renders the mice more susceptible to infections. Therefore, it is imperative for individuals with chronic skin inflammation to closely monitor disease progression upon infection and seek timely and appropriate treatment. Additionally, chronic inflammation of adipose tissue, induced by high-fat food intake, combined with dermatitis inflammation, may exacerbate infections, necessitating a review of dietary habits.

Clinical features, paraclinical characteristics, and etiology of mediastinal bleeding diffusion in children at the Vietnam National Children’s Hospital from 2018 to 2023

Background: In modern life, diffuse alveolar haemorrhage (DAH) is a serious and rare condition in children. Due to the subtle clinical manifestations and diverse causes of the disease, it is easy to be missed or diagnosed late. This study describes clinical and paraclinical characteristics, with the aim to find signs suggesting early diagnosis as well as determine the cause of DAH in children. Objects and methods: Case series. Results: From January 2018 to March 2023, there were 14 children diagnosed with DAH. The age of onset is 4.08 (1.58-5.41) years old, but most patients are diagnosed late with age at diagnosis being 5.25 (1.67-6.16) years old, male/female ratio is 1:1.8. The most common symptoms reported were anaemia (100%), hemoptysis (57.1%), shortness of breath (71.4%), and respiratory failure (85.7%). The common X-ray finding was diffuse infiltrates in both lungs (92.9%). On chest computed tomography scans, 92.9% of patients exhibited images of blurred opacity spreading, 57.1% showed interlobar pleural thickening, and 28.6% presented with images of lung consolidation. 3 patients (22%) had milk allergy, 2 patients (14%) had ANCA (Anti-neutrophil cytoplasmic antibody) vasculitis, and 9 patients (64%) had idiopathic pulmonary haemosiderosis (IPH).

Risk factors of diffuse alveolar hemorrhage in Chinese patients with systemic lupus erythematosus

This study aimed to investigate the frequency and features of diffuse alveolar hemorrhage (DAH) in Chinese patients with systemic lupus erythematosus (SLE) and evaluate the association of DAH with the features. A total of 943 patients with SLE were categorized into two groups: 896 patients without DAH and 47 patients with DAH. The demographic data, clinical and laboratory findings, and SLE disease activity index 2000 of all patients were statistically analyzed. The DAH frequency in patients with SLE was 4.98%, and the mortality rate of DAH was 42.55%. The clinical features with statistical differences between the two groups were analyzed by multivariate logistic regression, and the results suggested that shorter disease duration [odds ratio (OR): 0.972, 95% confidence interval (CI) 0.946, 0.998], younger age (OR: 0.867, 95% CI 0.764, 0.984), moderate (OR: 25.949, 95% CI 3.316, 203.065) or severe (OR: 24.904, 95% CI 2.675, 231.859) anemia, abnormally elevated levels of urine protein (OR: 10.839, 95% CI 1.351, 86.938) and serum creatinine (OR: 14.534, 95% CI 5.012, 42.142), interstitial lung disease (OR: 6.569, 95% CI 2.053, 21.021), and infection (OR: 8.890, 95% CI 3.580, 22.077) were independent risk factors for the occurrence of DAH in patients with SLE. Moderate or severe anemia was highly suggestive of DAH.

Prevalence of lung lesions at autopsy: A histopathological study

Introduction: Infections, occupational diseases and neoplastic lesions are common in lungs. In Autopsy internal organs including lungs are studied to determine cause of death and to study prevalence of various lung lesions. So, prophylactic prevention plan can be prepared for prevention of various lung lesions induced mortality and reducing need for invasive biopsy as well. Materials and Methods: This retrospective study was carried out in Pathology department. Tissue bits from lungs, retrieved at the time of autopsy, were preserved in 10% formalin, processed and examined microscopically. A total of 200 cases were received during the period of June 2021 to October 2022. Results: Among these 200 cases, in 10 cases (5%) the tissue was autolysed. Wide spectrum of microscopic findings were seen, the commonest being congestion (39%) followed by pneumonia (19.5%). There were 13% cases of inflammation in which 5.5% are of granulomatous type. There were 3% cases of intra alveolar hemorrhage and around 0.5% cases of interstitial fibrosis. The study also had 3.5% cases of malignancies. Conclusion: This study highlights various lesions in lungs confirmed by histopathology, which were either incidental or direct cause of death. The shortcoming in present study was non receipt of whole organ or representative sample at the time of autopsy, which if overcome will set much higher standard of autopsy reporting and would be a more useful tool in understanding cause of death. Key words: Histopathology, Medicolegal autopsy, Lung lesions.

Potential mechanisms of lung injury and repair after hexavalent chromium [Cr(VI)] aerosol whole-body dynamic exposure

Hexavalent chromium [Cr(VI)], known as "Top Hazardous Substances", poses a significant threat to the respiratory system. Nevertheless, the potential mechanisms of toxicity and the lung's repair ability after injury remain incompletely understood. In this study, Cr(VI) aerosol whole-body dynamic exposure system simulating real exposure scenarios of chromate workers was constructed to evaluate the lung injury and repair effects. Subsequently, miRNA sequencing, mRNA sequencing and metabolomics analyses on lung tissue were performed to explore the underlying mechanisms. Our results revealed that Cr(VI) exposure led to an increase in lactic dehydrogenase activity and a time-dependent decline in lung function. Notably, after 13 w of Cr(VI) exposure, alveolar hemorrhage, thickening of alveolar walls, emphysema-like changes, mitochondrial damage of alveolar epithelial cells and macrophage polarization changes were observed. Remarkably, a two-week repair intervention effectively ameliorated lung function decline and pulmonary injury. Furthermore, significant disruptions in the expressions of miRNAs and mRNAs involved in oxidative phosphorylation, glycerophospholipid metabolism and inflammatory signaling pathways were found. The two-week repair period resulted in the reversal of expression of oxidative phosphorylation related genes, and inhibited the inflammatory signaling pathways. This study concluded that the inhibition of the mitochondrial oxidative phosphorylation pathway and the subsequent enhancement of inflammatory response might be key mechanisms underlying Cr(VI) pulmonary toxicity, and timely cessation of exposure could effectively alleviate the pulmonary injury. These findings shed light on the potential mechanisms of Cr(VI) toxicity and provide crucial insights into the health protection for occupational populations exposed to Cr(VI).

Late Onset Systemic Lupus Erythematosus - Clinical and Autoantibody Profile and its Comparison with Young Onset Systemic Lupus Erythematosus.

The aim of the study was to determine the clinical features & autoantibody profile of patients having late onset Systemic Lupus Erythematosus (SLE) and to compare with young onset SLE due to its scarce data from India. All patients who fulfilled the 1997 ACR criteria for SLE were included. Late onset patients were >50 years of age and young onset were <50 years >18 years at the time of first SLE-related symptom. Clinical, laboratory, and autoantibody (ENA 25 & APLA) profiles were compared between the two groups using descriptive statistics and chi square test. Of the 305 patients, 69 had late onset (75.4% females). Mean age was 59.42±6.7 years (Late onset lupus) and 33.13±8.44 years (young onset lupus). The most common symptom was arthritis (60%) followed by oral ulceration (50%), fever (43%), and serositis (37.68%). Most common antibody was SSA/Ro60 (50%) and anti-SSA/Ro52 (46%). Interstitial lung disease (ILD) (14.5%), pancytopenia (13%) and diffuse alveolar haemorrhage (4.3%) were more frequent in late onset group. Statistically significant differences were found between two groups in terms of photosensitivity (p=0.009), malar rash (p=0.005), excessive hair loss (p=0.0006), Raynaud's phenomenon (p=0.001), lymphadenopathy (p=0.01), nephritis (p=0.0007), ILD (p=0.01), anti-dsDNA (p=0.005), anti-nucleosome (p=0.01), anti-Sm (p=0.007), Ribosomes P0 (p=0.0004). This study suggests that late onset SLE has distinct clinical and serological manifestations when compared with young onset SLE patients.

Deposition of Sevelamer crystals in gastrointestinal tract and lung parenchyma: A rare autopsy finding

Abstract Introduction/Objective Sevelamer carbonate is a non-calcium-based phosphate binder used for the management of hyperphosphatemia in patients with end stage renal disease. The well-known side effects of sevelamer include nausea, vomiting and abdominal pain. However, there are few case reports which described the deposition of sevelamer crystals in the gastrointestinal tract causing mucosal injury, pseudotumor or obstruction. Methods/Case Report We hereby present a case of a 43-year-old decedent female with past medical history of seizures, hypertension, cocaine use, type B aortic dissection status post thoracic endovascular aortic repair, total arch replacement, reconstruction of innominate, carotid, and subclavian artery who presented with hematochezia concerning for possible aorto-esophageal fistula on 10/06/2022 and acute kidney injury. Imaging showed a thrombus in mid-esophagus, blood in trachea and narrowing of the left main stem bronchus. Labs revealed worsening of BUN and creatinine and up trending hyperphosphatemia and therefore sevelamer carbonate via nasogastric route was started on 10/13/22. Unfortunately, the patient’s hospital course was complicated, and she passed away on 11/14/2022. At autopsy, the deceased had gross evidence of acute lung injury with diffuse alveolar hemorrhage, aorta-bronchial ruptured aneurysm defect and aorto-esophageal fistulas. On histopathological examination, the stomach, small and large bowel showed autolysis, necrosis, and numerous rectangular shaped, non-polarizable crystals. The crystals with characteristic morphology of “fish scale” with hues of pink in the center and yellow to orange in the periphery were identified as sevelamer crystals. Interestingly, crystal deposition was also identified in lung parenchyma and rarely in aortic wall and the fistula. Results (if a Case Study enter NA) NA Conclusion As one of the more commonly used resins in end stage kidney disease, gastrointestinal adverse effect of sevelamer carbonate is often underrecognized. Our case report heightens the awareness of the characteristic morphology of this biologically inert agent, sevelamer to those who are unaware of their morphology. This case also highlights the adverse effect of sevelamer in all patients presenting with gastrointestinal symptoms, such as gastrointestinal bleeding and abdominal pain with the use of sevelamer.

TLR3-Dependent Induction of TF Is Required to Maintain Lung Hemostasis during Poly IC-Induced ARDS-like Lung Dysfunction in Mice

Background: Respiratory virus infection causes damage to the epithelial-endothelial barrier of the lung. Mice challenged with influenza A virus (IAV) exhibit bleeding in the airspace. IAV increases tissue factor (TF) expression in epithelial cells (EpC) of the lung and deletion of lung EpC TF is associated with increased bleeding. aThe ssRNA viruses IAV undergo a dsRNA genomic phase during viral replication. Poly IC is a chemical mimetic of dsRNA. dsRNA acts like PAMPs and can activate the innate immune receptor, toll-like receptor 3 (TLR3). TLR3 stimulation of endothelial cells increased TF expression. However, the role of TLR3 in virus-induced TF expression in the lung TF has not been studied. Aim: To investigate the role of TLR3 in induction of TF during poly IC induced acute respiratory distress syndrome (ARDS)-like lung dysfunction in mice Methods: The murine lung EpC line, E10, was treated with the dsRNA mimetic (5 µg/mL), poly IC, for 0-6h. TF expression was measured by western blotting and a one-stage plasma clotting assay. Wild-type (WT) mice, mice with lung EpC TF deletion (TF fl/fl;SPCCre +, TFΔEpC) and their controls (TFfl/fl) as wells as TLR3 +/+ and TLR3 -/- mice were used in the study. To induce ARDS, poly IC (100 µg in 50 µL PBS) was administered intranasally daily for 3 days to adult mice (both sexes). Lung function was recorded noninvasively using the Buxco whole-body plethysmography system and plasma and bronchoalveolar lavage fluid (BALF) were collected before and 24 hours after the last administration of poly IC. Cellular composition of the BALF and blood was analyzed by an automated cell counter. Lung TF activity was quantified by one-stage plasma clotting and TF activity of extracellular vesicles (EV-TF) was analyzed by two-stage FXa generation assay. Results: Poly IC stimulation induced NFκB-dependent TF expression in E10 cells in dose and time-dependent manner. In addition, poly IC administration induced ARDS-like lung dysfunction, local lung inflammation and coagulation activation in WT mice compared to PBS-treated WT mice. Lung TF activity was increased 2-fold after poly IC administration compared to PBS-treated mice. Mice with lung EpC TF deficiency (TFΔEpC) did not exhibit an increase in lung TF or EV-TF in BALF after poly IC administration compared to controls. Importantly, TFΔEpC mice exhibited reduced activation of coagulation, impaired pulmonary hemostasis and increased hemorrhage into the airspace after poly IC compared to their littermate controls. In addition, TFΔEpC mice showed increased signs of poly IC-induced ARDS and had reduced lung function, increased lung injury and local inflammation compared to their control mice after poly IC. TLR3 -/- mice had significantly less EV-TF activity and less thrombin-antithrombin complexes (TAT) in BALF compared to TLR3 +/+ mice after poly IC. Conclusion: We show that the dsRNA mimetic poly IC induces lung EpC TF expression in vitro and vivo in part via TLR3-dependent NFκB pathway activation. TLR3 stimulation by intranasal poly IC results in sterile inflammation, and ARDS-like phenotype in mice similarly to that observed after IAV infection. Importantly, a deficiency in lung EpC TF leads to impaired lung hemostasis that is associated with an increased poly IC-induced ARDS phenotype as seen previously in our studies using IAV infection of mice. dsRNA induces induction of lung TF via TLR3. We proposed that induction of TF expression in the lung during respiratory viral infections protects against alveolar hemorrhage but can also contribute to thrombosis.

Gemtuzumab Ozogamicin for Patients with Newly Diagnosed CD33 Positive Acute Myeloid Leukemia: Results from a French Retrospective Observational Study

Introduction: Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate targeting CD33 with a calicheamicin derivative payload. GO is approved in France in combination with daunorubicin and cytarabine for treatment-naïve patients aged ≥15 years with de novo CD33-positive acute myeloid leukemia (AML). Before the European Medicines Agency granted marketing authorization in 2018, GO was available in France with an authorization for temporary use (ATU) for specific patients since 2010, and between 2018 and 2019 as part of a “post-ATU” cohort until its reimbursement. This study aimed to describe the real-world use, effectiveness, and safety of GO in treatment-naïve patients with CD33-positive AML in France, as requested by the French Transparency Commission. Methods: This retrospective, multicenter, observational study included all patients in the French ATU and post-ATU cohorts treated between 01 December 2014 and 31 October 2022. Patient and disease characteristics, treatment (dose/combination), response outcomes, and adverse events (AEs) of interest were described. Prognostic factors for event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) were identified using Cox proportional hazard models. Results: Overall, 113 patients were included (ATU cohort, N=62; post-ATU cohort, N=51). The median age when GO was initiated was 63.0 years (range, 19-91); 54.9% (n=62) of patients were male; 81.8% (n=72/88) had an ECOG performance score 0-1, and 65.3% (n=64/98) had favorable risk according to the ELN classification 2017 ( Table). During the first induction treatment, most patients (98.1%; n=105/107) received GO in association with other agents, most commonly cytarabine and daunorubicin (60.0%; n=63/105). Most patients (78.5%, n=84/107) received 3 doses of GO during first induction. In all cases, patients received GO in second (7.1%; n=8) or subsequent (2.7%; n=3) induction courses - always in association with cytarabine and with or without daunorubicin/other agents. GO was given during the first, second, and subsequent consolidation treatment in 46.9% (n=53), 32.7% (n=37), and 2.7% (n=3) of patients, respectively, usually with cytarabine with or without daunorubicin. After a median follow-up of 44.6 months (95% CI, 33.8-69.3), 78.6% (n=88/112) of patients responded post-induction - of these, 72.3% (n=81) achieved a complete response (CR) and 6.3% (n=7) achieved a CR without platelet recovery. Minimal residual disease was evaluable in 46 patients; 52.2% (n=24) achieved a CR without minimal residual disease. Median EFS was 13.1 months (95% CI, 9.9-17.5); EFS by ELN risk group is shown in the Table. Median RFS was 17.5 months (95% CI, 12.6-35.6) and median OS was 49.8 months (95% CI, 21.8-not estimable; Figure). After a median period of 13.0 months (range, 3.0-33.0) following GO treatment, 31.5% (n=35/111) of patients received a hematopoietic stem cell transplant. Older age predicted shorter OS (hazard ratio [HR] 1.1 [95% CI, 1.0-1.1]; p&amp;lt;0.001). Having an FLT3TKD mutation (HR 4.1 [95% CI, 1.4-12.4]; p=0.013) or adverse cytogenetic classification (HR 13.0 [95% CI, 2.3-73.8]; p=0.015) predicted shorter EFS. Having ECOG-PS ≥2 (HR 6.6 [95% CI, 1.8-24.5]; p=0.005) or adverse cytogenetic classification (HR 72.7 [95% CI, 7.6-699.1]; p=0.001) predicted shorter RFS. AEs of interest were reported for 38.9% (n=44) of patients; 13.3% (n=15) were serious and 26.6% (n=30) were treatment-related (TRAE). The most common AEs were thrombocytopenia (21.2%; n=24), pyrexia (4.4%; n=5), and hepatic cytolysis (3.5%; n=4). AEs of special interest included persistent thrombocytopenia (15.9%; n=18), severe hemorrhage (5.3%; n=6), and veno-occlusive disease/sinusoidal obstruction syndrome (0.9%; n=1). Overall, 46.9% (n=53) patients died, with relapse or progressive disease accounting for 41.5% of deaths (n=22/53). Two (1.8%) patients died from TRAEs (laryngeal edema/pulmonary alveolar hemorrhage and hepatic cytolysis). Conclusions: GO was predominantly administered according to its indication. Response rates were similar to those reported in the pivotal ALFA-0701 study. Median OS was longer in this study than in ALFA-0701 (49.8 vs 27.5 months), although median RFS and EFS were reduced. No new safety signals were reported. Overall, GO appears safe and effective in real-world practice when added to induction therapy for treating patients with de novo CD33-positive AML.

Infectious and Non-Infectious Pulmonary Complications in HCT Patients Treated with Post Transplant Cyclophosphamide (PTCy) Based Gvhd Prophylaxis

Introduction: Pulmonary complications are a leading cause of mortality and morbidity amongst pts undergoing hematopoietic stem cell transplantation (HCT). Increasingly, allogeneic HCT recipients are undergoing HCT with PTCy based GVHD prophylaxis. While lower rates of severe GVHD has been reported with PTCy, increased infection and organ toxicity has also been seen compared with standard calcineurin inhibitor (CNI) prophylaxis. The incidence and outcomes of pulmonary complications, both infectious and non-infectious/immune in pts receiving PTCy remain poorly characterized. Therefore, we aimed to assess for these in this study. Methods: We performed a retrospective review of pts between 2012-2022 who underwent 1st allogeneic BMT and received PTCy as part of GVHD prophylaxis. We identified pts requiring hospitalization for pulmonary complications. Infectious cases were categorized as bacterial, fungal, viral, or mixed. Bacterial pneumonia was defined as fever, cough, dyspnea, purulence sputum, and new or progressive radiographic evidence of infiltrate not explained by a non-infectious cause, treated with at least 5 days of antibiotics. Viral and fungal pneumonia were diagnosed based on identified organism. Noninfectious complications included idiopathic pulmonary syndrome (IPS), diffuse alveolar hemorrhage (DAH), cryptogenic organizing pneumonia (COP), and bronchiolitis obliterans syndrome (BOS). IPS was defined as radiographic evidence of alveolar infiltrates, dyspnea, cough, increased work of breathing or oxygen requirements, exclusion of infection or alternate pathology, and treated with high-dose systemic corticosteroids. DAH was defined as radiographic evidence of widespread alveolar injury, increased work of breathing or oxygen requirements, and persistent and progressive bloody return on BAL. COP was defined as pathologic evidence of organizing pneumonia on transbronchial lung biopsy in the absence of pathogens. BOS was defined as FEV1/FVC &amp;lt;0.7 and FEV1 &amp;lt;75% with a ≥10% decline over &amp;lt;2 years. Results: A total of 224 pts were identified. Median age at HCT was 55 years (20-78) (Table 1). 138 (64%) were male. The median comorbidity index (HCT-CI) score was 3 and median Karnofsky Performance Score was 80. 56%(n=125) pts underwent HCT with nonmyoablative conditioning, 78% (n=157) underwent HCT with a haploidentical donor, and 65% (n=145) of grafts were peripheral blood. 4%(n=10) were current smokers at time of HCT, 38% (n=84) were former smokers. 16% (n=35) had an existing diagnosis of asthma or COPD. 72 (32%) pts were hospitalized for pneumonia at any point after HCT. There were 23 bacterial pneumonias (30%), 20 viral (27%), 13 fungal (18%), and 12 were mixed (17%) (Table 2). There were 4 pts (6%)with documented pneumonia of unknown etiology due to rapid progression to death or hospice. 10 pts (4%) developed IPS with a median onset of 153 days (20-354). 2 pts (1%) developed COP with a mean onset of 754 days (388 - 1119). 5 pts (2%) developed BOS with a median onset of 336 days (153-677). 8 pts (4%) developed DAH with a median onset of 48 days (20-152). Among all patients, 57 pts (25%) required mechanical ventilation at any point post-HCT, and 18 pts (8%) were prescribed home oxygen at any point post-HCT. Overall, 80pts (77%) died due to non-relapse causes. 29 deaths (28%) were pulmonary related, (21 (20%) infectious and 8 (8%) noninfectious). Of the noninfectious pulmonary deaths, 3 pts died due to IPS, and 5 died due to DAH. Conclusion: In our cohort of pts receiving PTCy based GVHD prophylaxis, significant infectious pulmonary complications were common and were fatal in 9.4% of pts. Infections were the major driver of pulmonary related mortality, however, we observed noninfectious/immunologic pulmonary complications at a rate within or only slightly below the previously reported ranges among transplanted pts predominantly receiving CNI based prophylaxis.

Adverse Drug Effect Profiles of Gp2b/3a Inhibitors: A Comparative Review of the Last Two Decades.

ST-Elevation Myocardial Infarction and non-ST Elevation Myocardial Infarction belong to the acute coronary syndrome group of diseases. These conditions are characterized by the complete or partial blockage of one or several coronary arteries, resulting in myocardial injury or necrosis. Various medications are used in their treatment, with the most recent addition being Glycoprotein IIb/IIIa inhibitors. They work by hindering the activity of glycoprotein IIb/IIIa receptors, which, in turn, prevents the clumping of platelets. Some of the GpIIb/IIIa inhibitors available in this category include abciximab, tirofiban, eptifibatide, roxifiban, and orbofiban. With this comprehensive literature review, we aimed to explore the potential adverse effects of these medications and compare the three in terms of their side effects profile. We searched through PubMed and Google Scholar and pinpointed 13 articles aligned with our inclusion criteria: six articles utilized eptifibatide, four were related to abciximab, and three used tirofiban. In 85% of the cases, a severe drop in platelet count, reaching as low as 1000/μL, was reported. Additionally, several other side effects were noted: one case documented multiple bruising spots appearing around the patient's body, two cases reported diffuse alveolar hemorrhage, and one case described a cardiac tamponade resulting from hemorrhagic pericarditis. Our study highlights the crucial significance of keeping a watchful eye on and comprehending the potential drawbacks linked to these medications in cardiovascular treatment. The necessity of researching these medications and their side effects is also evident, as this will significantly enhance the quality of treatment provided.

Lesión pulmonar autoinducida por el paciente (P-SILI)

The article reviews the scientific literature on Patient Self-Induced Lung Injury (P-SILI) in patients with Acute Respiratory Distress Syndrome (ARDS). It begins with a history since 1985, highlighting events of pulmonary edema related to hyperventilation in diabetic patients and advances in the understanding of pulmonary mechanics. Experimental studies in sheep and humans are detailed that show lung damage due to hyperventilation, highlighting the importance of spontaneous ventilation and alveolar damage. In addition, studies on alveolar hemorrhage post-intense exercise in animals and high-performance athletes are mentioned. The text explores the relationship between Invasive Mechanical Ventilation (IMV) and lung injury, addressing therapeutic strategies such as neuromuscular blockade and the impact of positive end-expiratory pressure (PEEP). The theoretical mechanisms of P-SILI are delved into, highlighting pulmonary overdistension, increased pulmonary perfusion and patient-ventilator asynchronies. The clinical impact of P-SILI, especially in patients with COVID-19 and ARDS, is discussed, and management strategies such as high-flow oxygen therapy are highlighted. The article concludes by highlighting the need for more studies to standardize the monitoring of inspiratory efforts, understand its implication in prognosis and guide appropriate therapy, recognizing that the optimal approach is still the subject of debate.

Thrombotic Microangiopathy After Hematopoietic Stem Cell and Solid Organ Transplantation: A Review for Intensive Care Physicians.

Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies.

Galgravin Isolated from Piper kadsura Ameliorates Lipopolysaccharide (LPS)-Induced Endotoxemia in Mice

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.

Quick response to rituximab in a patient with Ro52-Jo1 complex-associated antisynthetase syndrome debuting with rapidly progressive interstitial lung disease and diffuse alveolar haemorrhage

Quick response to rituximab in a patient with Ro52-Jo1 complex-associated antisynthetase syndrome debuting with rapidly progressive interstitial lung disease and diffuse alveolar haemorrhage

Pneumorenal Syndrome Complicating ANCA-Negative Pauci-Immune Vasculitis Associated with Atypical Mycobacteriosis: Case Report

Among the forms of pneumorenal syndrome (PRS), one of the most urgent is characterized by the combination of diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis (RPGN). In 90% of cases, it is the manifestation of an autoimmune disease, such as pauci-immune vasculitis with anti-neutrophil cytoplasmic antibodies (ANCA) or Goodpasture's disease with the presence of antibodies directed against the basement membrane of the glomerular and alveolar capillaries (anti-GBM). These antibodies are absent in approximately 10% of cases with histological confirmation in the context of rare clinical situations. We report a case of a 66-year-old patient, with a history of alcoholism and active smoking, who was admitted to the hospital for respiratory distress with hemoptysis. The admission assessment showed severe renal failure requiring hemodialysis upon admission. ANCA and anti-GBM, as well as all other autoantibodies were negative. A renal biopsy revealed pauci-immune extra-capillary glomerulonephritis with the majority of chronic lesions. The orientation of the diagnostic approach in search of other causes of pauci-immune vasculitis with negative antibodies has been initiated. He was treated with glucocorticoids in combination with cyclophosphamide. The initial evolution was marked by the improvement of respiratory symptoms and a less considerable recovery of renal function. PRS can develop without the presence of ANCA or other autoantibodies. The diagnosis is then made by histology. Renal damage, such as extra-capillary glomerulonephritis (GN), is more severe and has a very poor prognosis with a high risk of mortality. The absence of ANCA should never delay diagnosis and treatment.

Purtscher-like retinopathy and paracentral acute middle maculopathy following breast filler injection

BackgroundTo report a rare case of pulmonary and ocular complications with visual loss due to bilateral Purtscher-like retinopathy and paracentral acute middle maculopathy (PAMM) following a hyaluronic acid (HA) filler injection to the breast. Systemic and visual recovery was attained following corticosteroid therapy.Case presentationA 27-year-old lady presented with painless blurring of vision in both eyes for 2 weeks following hyaluronic acid breast filler injections by a non-medical practitioner. She was initially admitted to the medical ward for diffuse alveolar haemorrhage and altered sensorium. The presenting visual acuity was counting fingers in both eyes. Bilateral dilated fundus examination showed hyperaemic discs, concentric rim of retinal whitening around macula with patches of polygonal-shaped retinal whitening, generalised cotton-wool spots, tortuous veins, and flame-shaped haemorrhages. Spectral-domain optical coherence tomography (SD-OCT) macula revealed hyper-reflective bands at the inner nuclear layer (INL). Fluorescein angiography demonstrated hot discs, delayed arm-to-retina time, arterial filling, and arterio-venous transit time with staining of the vessels at the posterior pole. She was managed with a tapering dose of systemic corticosteroids. The visual acuity improved to 6/12 over 8 weeks with significant anatomical and functional improvement. Dilated fundus examination showed resolution of initial funduscopy findings. The hyper-reflective bands on the OCT had resolved with subsequent thinning of the INL and disorganisation of retinal inner layers.ConclusionFiller injections are in increasing demand and are frequently being performed by non-medical practitioners. Visual loss from non-facial HA fillers is rare. Inadvertent entry of HA into a blood vessel may potentially cause systemic and sight-threatening ocular complications. Good anatomical knowledge and proper injection technique are vital in preventing this unfortunate sequela. There are limited reports on successful visual recovery following various treatment approaches and we hope this case provides valuable insights.

Abstract 12001: To Bleed or Not to Bleed: The Challenging Management of Saddle Pulmonary Embolism in a Patient With Widely Metastatic Breast Cancer

Introduction: In patients with high-risk pulmonary embolism (PE), anticoagulation (AC) is the mainstay of treatment before and after systemic thrombolysis and/or catheter-directed therapy. Our case highlights a challenging clinical decision where AC had to be initiated due to hemodynamic instability despite its controversial role in patients with CNS metastases. Case Description: A 52 years old female with ER+/PR+/HER2- breast cancer with widespread brain &amp; vertebral metastases presented after a syncopal event. She had tachycardia and hypotension necessitating IV fluids and vasopressors. Echocardiogram showed RV dilation with reduced systolic function &amp; septal wall motion concerning for RV pressure overload. CTA of chest showed large saddle PE with extension into bilateral segmental arteries and enlarged RV. Significant labs: Troponin-I 1.64 ng/mL, BNP 186 pg/mL, hemoglobin 8 g/dL, and platelets 54,000/μl. She was initiated on IV heparin but given worsening hemodynamic instability, she underwent catheter-based thrombectomy with improvement in hemodynamics. Serial CT head showed no evidence of intracranial hemorrhage but she developed diffuse alveolar hemorrhage necessitating intubation. Her bleeding eventually resolved, and she was extubated and discharged on DOAC. Discussion: This patient had high-risk PE given her hemodynamic instability, elevation in cardiac biomarkers, and RV strain on imaging. Treatment includes AC followed by systemic thrombolysis or catheter-directed therapy followed by AC. This patient’s management was complicated due to widespread metastases, thrombocytopenia and anemia. AC was nonetheless initiated due to her hemodynamic instability and patient eventually required thrombectomy. Conclusion: Brain metastases are an absolute contraindication to systemic thrombolysis, but the role of systemic AC is controversial. Our case highlights the importance of personalized decision-making regarding AC.

Abstract 13671: A Case of Diffuse Alveolar Hemorrhage While on Systemic Anticoagulation for Impella

A 57 year old male with PMH of non-ischemic cardiomyopathy (EF 30%), atrial fibrillation, and VT s/p ICD was admitted to the cardiac intensive care unit for cardiogenic shock. His condition deteriorated necessitating Impella 5.5 implantation as bridge to cardiac transplant. Systemic heparin was started per Impella protocol with a lower anti-Xa goal of 0.2 - 0.3 given post-op bleeding at the R axillary Impella site. Five days post Impella placement he developed bloody secretions from the endotracheal tube requiring multiple blood transfusions and discontinuation of systemic heparin, while maintaining heparin purge. Labs were notable for anti-Xa 0.22, hemoglobin 9.7, and platelets 221. CT Chest demonstrated parenchymal opacities concerning for diffuse alveolar hemorrhage (DAH) which was confirmed via bronchoalveolar lavage; he had no known history of lung disease. High-dose corticosteroids were administered as a high ANA titer (1:128) and low C3 suggested capillaritis. However, decreasing ANA (1: 320) and a negative autoimmune workup decreased the likelihood of a rheumatologic cause for DAH and steroids were discontinued. DAH secondary to acquired von Willebrand syndrome (aVWS) was considered, but factor VIII and vWF activity levels were normal. The bloody secretions improved with inhaled thromboxane and systemic heparin was restarted. Orthotopic heart and kidney transplant was performed with subsequent Impella removal 104 days after Impella placement. Discussion: We present the first documented case of DAH with isolated Impella 5.5 support. Previously reported cases of DAH post-Impella were observed in patients with concurrent ECMO or RVAD. As autoimmune and coagulopathic causes of DAH were excluded, bland DAH secondary to systemic anticoagulation is most likely in this case. This raises a question about how to balance the risk of bleeding with the risk of device thrombosis, stroke and embolic events and when to switch from heparin to sodium bicarbonate purge.

Autopsy Histopathologic Lung Findings in Patients Treated With Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in the treatment of respiratory and cardiac failure, but data describing lung histopathology in ECMO recipients are limited. To examine pulmonary histopathologic findings in patients who underwent venovenous (VV) ECMO for pulmonary reasons or venoarterial (VA) ECMO for cardiac indications shortly before death, and to determine if the pulmonary changes provided insights into therapy that may prevent complications and improve outcome. We conducted a retrospective study of lung autopsies, from VV and VA ECMO recipients and patients with acute respiratory distress syndrome (ARDS) and non-ECMO treatment, between 2008 and 2020 in Silesia Center for Heart Diseases in Zabrze, Poland. Among 83 ECMO patients (42-64 years; men, 57 [68.7%]), the most common histopathologic findings were bronchopneumonia (44 [53.0%]), interstitial edema (40 [48.2%]), diffuse alveolar damage (DAD; 32 [38.6%]), hemorrhagic infarct (28 [33.7%]), and pulmonary hemorrhage (25 [30.1%]). DAD was associated with longer ECMO treatment and longer hospital stay. The use of VV ECMO was a predictor of DAD in patients with ARDS and undergoing ECMO, but it also occurred in 21 of 65 patients (32.3%) in the VA ECMO group, even though VA ECMO was used for heart failure. Although DAD was significantly more common in lung autopsies of VV ECMO patients, one-third of VA ECMO patients had histopathologic changes characteristic of ARDS. The presence of DAD in lung autopsies of patients treated with VA ECMO indicates that in these patients, protective lung ventilation should be considered.