Pulmonary Alveolar Hemorrhage Research Articles

Late-Presenting Eosinophilic Granulomatosis with Polyangiitis as Cause of Pulmonary Fibrosis: A Case-Based Review.

Eosinophilic granulomatosis with polyangiitis (eGPA) is a necrotising vasculitis of small and medium calibre vessels, which affects mostly patients in their fourth to sixth decade of life, and it is a very uncommon aetiology for pulmonary fibrosis. A Hispanic 72-year-old female patient presents with a history of lower extremities pain, paraesthesia, oedema, and occasional macroscopic haematuria. During her hospitalisation, the patient presents, and images showed findings compatible with pulmonary fibrosis and alveolar haemorrhage, which require a biopsy, establishing the diagnosis of an eGPA. eGPA is a low-incidence autoimmune vasculitis, with a high number of phenotypes which explain the broad clinical spectrum, but recent advances has helped to understand the physiopathology and its link with other conditions like pulmonary fibrosis. Early diagnosis and management of this condition is mandatory because it is the only factor that change the outcome of the patients.

Lightning-strike induced acute injury: A case report

Lightning strike injury is a rare but a devastating lifethreatening condition affecting virtually all tissues and solid organs of the body. This can be attributed to the various energy transmission mechanisms from lightning strikes. This include ground strike, contact voltage, side flash, wire-mediated lightning, direct strike and weak upper streamer. Acute lung injury following lightning strike is an uncommon presentation which can manifest as pulmonary oedema, alveolar haemorrhage, pulmonary contusion and acute respiratory distress syndrome. This is a case report of a 15-year-old female, who presented to the Emergency CC –BY 4.0 unit following a lightning strike injury. She presented in coma from the referral centre, markedly dyspnoeic, and eventually admitted into the intensive care unit on account of respiratory failure. Chest radiograph findings showed features in-keeping with non- cardiogenic pulmonary oedema. She was mechanically ventilated, placed on steroids, hydrated, and given antibiotics. Following treatment, respiratory distress resolved and she regained full consciousness. She was discharged home after 11 days of admission.

Pulmonary involvement in catastrophic antiphospholipid syndrome: A descriptive analysis from the “CAPS Registry”

ObjectivesTo describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement, laboratory, radiological, and pathological findings. MethodsThis retrospective cross-sectional study includes all patients grouped in the “CAPS Registry”. All cases were reviewed, and those with pulmonary thromboembolism (PE) and/or diffuse alveolar hemorrhage (DAH) were selected. Data on pulmonary and extrapulmonary clinical presentation, radiologic patterns, laboratory findings, associated autoimmune diseases, treatments, and outcomes were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test, while T-test for independent variables was used to compare groups regarding continuous variables. IBM-SPSS v.22 was used for data analysis. ResultsPE was reported in 129 (48.6 %) episodes, DAH in 75 (28.3 %) episodes, and overlap (DAH plus PE) in 7 (2.6 %) episodes. Bronchoalveolar lavage (BAL) was performed in 35 (4.9 %) CAPS episodes, and lung pathology samples were obtained in 84 (10.5 %) episodes (including autopsies). A significant relationship was observed between DAH and laboratory features of thrombotic microangiopathy (TMA). A meaningful relationship was also found between triple antiphospholipid antibody positivity and pathological TMA (26.5 %) as well as hypocomplementemia and DAH (24 %). ConclusionsPulmonary involvement may include both TMA and non-thrombotic inflammation, which can be differentiated into three patterns: PE, DAH with systemic TMA with hypocomplementemia or DAH without systemic TMA with/without hypocomplementemia.

A booster administration of the OKA/SK strain causes fatal disseminated varicellain an immunocompetent child.

Live varicella vaccines are known to provide robust immunity against varicella zoster virus (VZV) infections. However, problems with viral attenuation have led to pathogenic VZV vaccine strains causing varicella-like rash and herpes zoster in immunocompetent children after immunization. We report the first fatal case of VZV infection caused by OKA/SK strain contained in the vaccine administrated as a booster shot in an immunocompetent child,which has been independently developed from any currently available varicella vaccines that are OKA strain or MAV/06 strain based. The patient died due to sudden pulmonary alveolar hemorrhage as a secondary complication of VZV pneumonitis. Sequencing of the four SNPs unique to the OKA/SK strain (SNP loci 14 035T; 32 626C; 58 777G; 70 319G) enabled discrimination of the strain responsible for the disseminated infection. OKA/SK strain does not have any SNPs in ORF62 postulated to be responsible for the attenuation of varicella vaccines which have been safely and effectively used world-wide or locally, and exclusively enriches a virulent factor in ORF31 identified in parental OKA strain, thus possibly resulting in disseminated VZV infection leading to mortality. Therefore, actions need to be taken to prevent vaccine related morbidity and mortality in children.

Negative pressure pulmonary oedema and alveolar haemorrhage due to upper airway obstruction after parathyroidectomy

36-year old female underwent elective parathyroidectomy at a Swiss tertiary teaching hospital for primary hyperparathyroid-ism. Induction, surgery and extubation were uneventful. During transfer to the post-anaesthetic care unit, some retching was interpreted as vomiting. At arrival, she was apnoeic and unresponsive but with palpable pulse.

A disproportionality analysis of the adverse effect profiles of methimazole and propylthiouracil in patients with hyperthyroidism using the Japanese Adverse Drug Event Report Database.

Antithyroid drugs (ATDs) are frequently used to achieve euthyroidism in patients with hyperthyroidism. ATDs cause characteristic common and rare adverse events; however, comprehensive comparisons between methimazole (MMI) and propylthiouracil (PTU) in terms of adverse events are limited. In this study, we thoroughly explored adverse events in association with MMI and PTU use with a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database and evaluated the prevalence of MMI and PTU prescriptions using the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. We analyzed 3271 cases of MMI use and 1029 cases of PTU use with respect to 9789 preferred terms (PTs) for adverse events registered in the JADER database by calculating and comparing reporting odds ratios (RORs). We found that 8 PTs, including agranulocytosis (p < 0.0001, 4.01-fold), aplasia cutis congenita (p < 0.0001, 123.22-fold), and exomphalos (p = 0.0002, 22.17-fold), demonstrated significantly higher RORs (more than 4-fold) for MMI use than for PTU use. Nineteen PTs, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (p < 0.0001, 29.84), rapidly progressive glomerulonephritis (p < 0.0001, 6.44), and pulmonary alveolar hemorrhage (p < 0.0001, 7.77), had RORs for PTU use more than four times those for MMI use. NDB Open Data Japan showed more frequent PTU prescriptions than MMI prescriptions for women of reproductive age. This large-scale study confirmed that a variety of congenital malformations were identified as having significantly high RORs for MMI use, while diseases related to ANCA-associated vasculitis were specific to PTU.

ЛЕГОЧНО-ПОЧЕЧНЫЙ СИНДРОМ, ОБУСЛОВЛЕННЫЙ АНТИ-ГБМ БОЛЕЗНЬЮ В СОЧЕТАНИИ С АНЦА-ВАСКУЛИТОМ ПОСЛЕ SARS-COV-2 ИНФЕКЦИИ

Introduction. Pulmonary-renal syndrome (PRS) manifested by a combination of idiopathic pulmonary alveolar hemorrhage and rapidly progressing glomerulonephritis, is most commonly associated with either anti-neutrophil cytoplasmic antibodies (ANCA) or anti-glomerular basement membrane (anti-GBM) antibodies. Despite the rather rarity of this disease, there is a sufficient number of observations with the simultaneous presence of both types of antibodies, the so-called double antibody-positive phenotype. During the pandemic of SARS-CoV-2 infection an increase in cases of PRS was noted, however, the phenomenon of double antibody positi¬vity – ANCA plus anti-GBM – is still a clinical casuistry. Observation. A 64-year-old woman was hospitalized 2 months after SARS-CoV-2 infection with PRS of a severe course with rapidly progressing renal failure, as well as lung affection with hemoptysis and typical changes on multidetector computed tomography. The patient was found to be double positive for ANCA and anti-GBM. Therapy including plasma exchanges, high doses of steroids and cyclophosphamide was carried out which gave a short-term improvement, but did not prevent dependence on hemodialysis. 7 months after the onset of PRS the patient died from a secondary infection. According to the pathoanatomical study, the diagnosis of anti-GBM disease in combination with ANCA-associated vasculitis was confirmed. Conclusion. As far as we know, this is the second reported case of 'double antibody' PRS after SARS-CoV-2 infection. We believe that in all such clinical situations it is necessary to test for both types of antibodies as this will determine the clinical tactics.

ENAMPT/TLR4 inflammatory cascade activation is a key contributor to SLE Lung vasculitis and alveolar hemorrhage

RationaleEffective therapies to reduce the severity and high mortality of pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) is a serious unmet need. We explored whether biologic neutralization of eNAMPT (extracellular nicotinamide phosphoribosyl-transferase), a novel DAMP and Toll-like receptor 4 ligand, represents a viable therapeutic strategy in lupus vasculitis. MethodsSerum was collected from SLE subjects (n = 37) for eNAMPT protein measurements. In the preclinical pristane-induced murine model of lung vasculitis/hemorrhage, C57BL/6 J mice (n = 5–10/group) were treated with PBS, IgG (1 mg/kg), or the eNAMPT-neutralizing ALT-100 mAb (1 mg/kg, IP or subcutaneously (SQ). Lung injury evaluation (Day 10) included histology/immuno-histochemistry, BAL protein/cellularity, tissue biochemistry, RNA sequencing, and plasma biomarker assessment. ResultsSLE subjects showed highly significant increases in blood NAMPT mRNA expression and eNAMPT protein levels compared to healthy controls. Preclinical pristane-exposed mice studies showed significantly increased NAMPT lung tissue expression and increased plasma eNAMPT levels accompanied by marked increases in alveolar hemorrhage and lung inflammation (BAL protein, PMNs, activated monocytes). In contrast, ALT-100 mAb-treated mice showed significant attenuation of inflammatory lung injury, alveolar hemorrhage, BAL protein, tissue leukocytes, and plasma inflammatory cytokines (eNAMPT, IL-6, IL-8). Lung RNA sequencing showed pristane-induced activation of inflammatory genes/pathways including NFkB, cytokine/chemokine, IL-1β, and MMP signaling pathways, each rectified in ALT-100 mAb-treated mice. ConclusionsThese findings highlight the role of eNAMPT/TLR4-mediated inflammatory signaling in the pathobiology of SLE pulmonary vasculitis and alveolar hemorrhage. Biologic neutralization of this novel DAMP appears to serve as a viable strategy to reduce the severity of SLE lung vasculitis.

Comparison of Therapeutic Efficacy between Hypomenthylating Agents Combined with Venetoclax and Half Dose Priming Regimen in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

To compare the clinical efficacy and safety of hypomenthylating agents (HMA) combined with Venetoclax (VEN) and half dose priming regimen (CAG-like) in the treatment of elderly patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for intensive chemotherapy. The clinical data of 43 newly diagnosed elderly patients with AML who were not suitable for intensive chemotherapy in our hospital from April 2019 to October 2020 were retrospectively analyzed. Among them, 16 cases received HMA-VEN regimen and 27 cases received HMA-CAG-like regimen. The remission rate, early mortality and survival were compared between the two groups. And, the patients were grouped according to HCT-CI score. The effects of two different regimens in different groups on the efficacy and survival of patients were compared, and the prognosis of patients was further analyzed. After one course of treatment, the total remission rate of HMA-VEN group and HMA-CAG-like group was 81.3% (13/16) and 51.9% (14/27), respectively, and the difference between the two groups was statistically significant (χ2=4.650, P=0.045). The median overall survival (OS) time of HMA-VEN group had not yet reached, while that of HMA-CAG-like group was 11.2 months, and the HMA-VEN group had a longer OS (P=0.055). There was no tumor lysis syndrome occurred in both groups. The main adverse reactions were digestive tract reaction, bone marrow suppression and infection. The amount of agranulocytosis infection, pulmonary infection and platelet infusion in HMA-VEN group were significantly lower than those in HMA-CAG-like group (P<0.05), while the time of agranulocytosis and amount of erythrocyte infusion were similar (P>0.05). In HMA-Ven group 1 case died early, while in HMA-CAG-like group 8 cases died early due to pulmonary infection, respiratory failure, cerebral hemorrhage, and alveolar hemorrhage, the mortality in HMA-CAG-like group was significantly higher than that in HMA-VEN group (P=0.043). Among 43 patients, there was a significant difference in OS between HCT score 0-2 group and ≥3 group (P=0.033). In HMA-CAG-like group, patients with HCT score ≥3 had a worse prognosis (P=0.01), while in HMA-VEN group patients showed no statistically significant difference in prognosis (P=0.681). In HCT score 0-2 group, 9 cases receiving HMA-VEN regimen and 22 cases receiving HMA-CAG-like regimen showed no statistical difference in OS (P=0.281). In HCT score ≥3 group, 7 cases receiving HMA-VEN regimen had a longer OS than 5 cases receiving HMA-CAG-like regimen (P=0.015). Venetoclax combined with HMA can achieve higher response rate, lower early mortality, and longer OS, especially in those with more comorbidities and poor tolerability.

Ruxolitinib for Myelofibrosis in Resource Limited Settings : A Slip between the Cup and the Lip

Background and Objective:Ruxolitnib, an orally bioavailable non-specific JAK inhibitor is a novel drug used for treating myelofibrosis by targeting the unique disease biology and has significantly reduced symptomatic burden in these patients. In resource limited countries, the data on post marketing experience with this relatively novel agent is limited. The major objectives of this study was to examine the challenges encountered with the use of Ruxolitinib in our resource limited setting. Methods:Patients with confirmed diagnosis of myelofibrosis and initiated on ruxolitinib therapy consecutively during the time period between December 2013 to March 2019 at our institute were included in the study. The data was collected from electronic medical records over a period of 12 months from March 2020 to March 2021. Results:This retrospective analysis included forty six patients and their baseline characteristics are summarized in Table 1. Twenty five (54.3%) patients received lower than the recommended dose for the corresponding platelet count. On response assessment, the mean MPN SAF ISS score showed reduction from 30 (6-64) to 15 (2-38).Among the 36 patients with splenomegaly documented in records, a spleen response below costal margin of <5cm was seen in 2 (5.5%), 5 - 10cm in 9 (25%) and >10cm in 22 (61.1%) patients. . The patients were followed up for a median of 29.5 months (0-76 months) after Ruxolitinib initiation.At the time of data locking, 12 (26%) patients were still on ruxolitinib, 13 (28.2%) patients were lost to follow up and 7 (15.2%) patients died. Rest of the fourteen (30.4%) patients discontinued ruxolitinib, the reasons being financial constraints in 7 (50%), disease progression in 3 (21.4%), haematological toxicity in 2 (14.2%) and intolerance due to non-haematological causes in 2 (14.2%). Haematological adverse events that necessitated dose reduction or cessation of drug were anemia and thrombocytopenia. The serious non-hematological adverse events were renal dysfunction, pancreatitis, COVID infection, DIC and pulmonary alveolar haemorrhage in one patient each and two cases of active tuberculosis. Seven (15.2%) patients died while on therapy or shortly after discontinuing ruxolitinib. The causes of death were pulmonary alveolar haemorrhage, disease progression, disseminated intravascular coagulation post cardiac valve surgery, pneumonia complicated by sepsis/ hemophagocytic lymphohistiocytosis (HLH) and COVID infection. Among these, 2 patients died within one month of stopping ruxolitinib. The possibility of ruxolitinib discontinuation syndrome (RDS) was considered retrospectively in these patients. The overall mean survival time was 145.4 ±16 months (95% CI: 114 - 176.8months). Discussion:At the time of last follow-up, more than half of the patients in our study group had either discontinued therapy or were lost to follow up. The most common reason for discontinuation was financial burden, the other reasons being disease progression and intolerance. In our setting, the patients entail an annual cost of approximately 2560 USD, 4530 USD and 4770 USD for 5mg BD, 15mg BD and 20mg BD respectively within patient assisted programs and much higher outside these programs. In a country like India with a nominal Gross Domestic Product (GDP) per capita of around 2191 USD, this not only reflects the high cost of the drug but also the discordant pricing of the different doses resulting in opting for lower doses. The financial burden of the drug is also reflected in the NICE Appraisal Committee recommendation that though ruxolitinib is clinically effective, it is not cost effective for symptomatic therapy CONCLUSION In spite of having a good symptom response, many of our patients discontinued the drug because of its "financial toxicity". In developing economies, better access to the drug and doing away with suboptimal doses need to be addressed so that the target population can reap its therapeutic effect in entirety. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Negative-pressure pulmonary edema and alveolar hemorrhage are potentially life-threatening complications of upper airway obstruction

Negative pressure pulmonary edema and alveolar hemorrhage are potentially life-threatening complications after relief of upper airway obstruction. The laryngeal-pharyngeal obstruction results in high negative intrapleural pressures. The increased intrapleural pressures affect the integrity of the alveolo-capillary membrane due to various factors. This review describes clinical symptoms, etiologic factors, pathophysiology and treatment strategies associated with each of these factors. The aim of this review is to equip clinicians with the knowledge base necessary to identify patients at increased risk for negative pressure pulmonary edema and alveolar hemorrhage.

LBODP104 Thyroid Plasmapheresis: An Alternative Option For Thyroid Storm

Abstract Introduction Thyroid storm is a rare, life-threatening condition with a high mortality rate approaching 10-30%. The mainstay of treatment includes initiation of therapy directed against the thyroid, supportive intensive care, and treatment of any precipitating factors. We report three cases of patients with thyroid storm and successful therapeutic use of plasmapheresis when traditional therapy was contraindicated. Clinical Cases Case 1 A 22-year-old male with no known past medical history, presented with fever, shortness of breath, and syncope. Labs showed TSH 0. 014 mIU/L (range 0.4-4.5), FT4 4.30 ng/dL (range 0.9-2.2), TSI 546% (range &amp;lt;140), and TPO 20 U/mL (range &amp;lt;60). He was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 60). He was initially treated with propylthiouracil (PTU), hydrocortisone, propranolol, and Lugol's iodine solution. He developed transaminitis and shock liver so was not able to continue PTU or trial methimazole. He underwent 4 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Case 2 A 37-year-old female with known Graves’ disease (non-adherent to antithyroid drug), presented with shortness of breath and palpitations. Labs showed TSH &amp;lt;0. 01 mIU/L (range 0.4-4.5), FT4 4.83 ng/dL (range 0.9-2.2), and FT3 6. 0 pg/mL (range 2.3-4.2). Burch-Wartofsky score was 40 and supported the diagnosis of thyroid storm. She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed transaminitis and there was also concern for methimazole-induced insulin autoimmune syndrome, so methimazole was discontinued. She underwent 3 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Case 3 A 31-year-old female with no known past medical history, presented with shortness of breath and altered mental status requiring intubation. Labs showed TSH &amp;lt;0. 01 mIU/L (range 0.4-4.5), FT4 4.65 ng/dL (range 0.9-2.2), FT3 25.2 pg/mL (range 2.3-4.2), TSI 467% (range &amp;lt;140), TPO 375 U/mL (range &amp;lt;60). She was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 90). She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed pulmonary alveolar hemorrhage and it was unclear if this was due to methimazole, thus methimazole was discontinued. She underwent 5 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy. Conclusion Plasmapheresis can be an effective and safe treatment option in thyroid storm when there are contraindications for antithyroid drugs or when rapid normalization of thyroid hormone levels is needed. It should be considered as a stabilizing measure as it leads to marked improvement of thyrotoxicosis within 3-5 days, allowing thyroidectomy for definitive therapy. Presentation: No date and time listed

The Accuracy 0f CT Chest in Determining Between Ground Glass Opacities And Those Caused by Covid-19 And Other Medications

Introduction: Diagnostic ct scanning of the chest is currently being investigated for its ability to distinguish between ground glass opacities (GGO) caused by coronavirus 2019 (COVID-19) and GGO produced by other causes. Place and Duration: From January 2022 until June 2022, I will work as a Radiologist at Qazi Hussain Ahmad Hospital in Nowshera. Methods: This study was cross sectional study carried out at the Qazi Hussain Ahmad Hospital, Nowshera for a period of six months. The overall sample size in the current study was100 non-contrast chest CTs. Eexperienced radiologists analyzed the CT images of the chest after redacting any personal information. laboratory results and the patient's medical history were noted. Results: The participants comprised 46 people with COVID19 and 100 without COVID19 who also had ground glass opacities on chest CT. There was no statistically significant difference in age between the groups (p-value = 0.212). Out of the non-COVID-19 GGO cases, three patients have hypersensitivity pneumonia in 3, eosinophilic pneumonia in 3, interstitial pneumonia in 7, pulmonary pneumonia in 3, pulmonary fibrosis in 7, drug-induced lung damage in 7, pulmonary alveolar hemorrhage in 3, and pulmonary emphysema in 11. Practical implication: This study will provide physician with the data to compare the likelihood that COVID-19 causes ground glass opacities on a chest CT scan versus the likelihood that they are caused by other probable causes Conclusion: Moreover, the specificity of chest CT in differentiating COVID-19 from viral pneumonia is only intermediate, and the specificity of chest CT in distinguishing COVID-19 from other reasons of ground glass opacities is poor. Keywords: CT Chest, Determining, Ground-Glass Opacities, Covid-19, Medications

Pulmonary Manifestations and Vascular Changes in Pediatric Transplantation-Associated Thrombotic Microangiopathy

Although transplant-associated thrombotic microangiopathy (TA-TMA) commonly complicates pediatric hematopoietic cellular therapy (HCT), pulmonary manifestations and histology of TA-TMA (pTA-TMA) are rarely reported, with scant data available on timing, risk factors, pathogenesis, and outcomes. Pulmonary hypertension (PH) and diffuse alveolar hemorrhage (DAH) are recognized manifestations of pTA-TMA. The objective of this study was to characterize the pathologic findings, outcomes, and coincident diagnoses preceding biopsy-proven pTA-TMA. In Institutional Review Board- approved retrospective studies, available lung tissue was reviewed at 2 institutions between January 2016 and August 2021 to include those with pulmonary vascular pathology. Histologic features of pTA-TMA were present in 10 children with prior respiratory decline after an allogeneic HCT (allo-HCT; n=9) or autologous HCT (n=1). Pathologic lesions included muscular medialization, microthrombi, and red cell fragments, in addition to perivasculitis and intimal arteritis. Parenchymal findings included diffuse alveolar damage, organizing pneumonia, and plasmocytic infiltrates. Six children were clinically diagnosed with TA-TMA, and all were treated with eculizumab, at a median of 2.5 days after clinical diagnosis (range, 0 to 11 days). Four were identified postmortem. Coincident pulmonary infection was confirmed in 8 of the 10 patients. Five allo-HCT recipients (56%) experienced graft-versus-host disease (GVHD; 4 acute, 1 chronic) prior to the onset of respiratory symptoms. Two patients (20%) had clinically recognized DAH, although 9 (90%) had evidence of DAH on histology. Although all 10 patients underwent echocardiography at the time of symptom onset and 9 had serial echocardiograms, only 2 patients had PH detected. Treatments varied and included sildenafil (n=3), steroids (n=1), and eculizumab (n=6). One patient was alive at the time of this report; the remaining 9 died, at a median of 52 days after onset of respiratory symptoms (range 4 to 440 days) and a median of 126 days post-HCT (range, 13 to 947 days). pTA-TMA is a heterogeneous histologic disease characterized by arteriolar inflammation, microthrombi, and often DAH. pTA-TMA presented with respiratory decline with systemic TA-TMA in all patients. Clinicians should maintain a high degree of suspicion for DAH in patients with TA-TMA and pulmonary symptoms. Coincident rates of GVHD and pulmonary infections were high, whereas the rate of PH identified by echocardiography was 20%. Outcomes were poor despite early use of eculizumab and other therapies. Our data merit consideration of pTA-TMA in patients with acute respiratory decline in the setting of systemic TA-TMA, GVHD, and infection. Investigation of additional therapies for pTA-TMA is needed as well. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme 2 (ACE2) as a main receptor to enter target cells. The goal of this study was to demonstrate the preclinical efficacy of a novel soluble ACE2 protein with increased duration of action and binding capacity in a lethal mouse model of COVID-19. A human soluble ACE2 variant fused with an albumin binding domain (ABD) was linked via a dimerization motif hinge-like 4-cysteine dodecapeptide (DDC) to improve binding capacity to SARS-CoV-2. This novel soluble ACE2 protein (ACE2-1-618-DDC-ABD) was then administered intranasally and intraperitoneally to mice before intranasal inoculation of SARS-CoV-2 and then for two additional days post viral inoculation. Untreated animals became severely ill, and all had to be humanely euthanized by day 6 or 7 and had pulmonary alveolar hemorrhage with mononuclear infiltrates. In contrast, all but one mouse infected with a lethal dose of SARS-CoV-2 that received ACE2-1-618-DDC-ABD survived. In the animals inoculated with SARS-CoV-2 that were untreated, viral titers were high in the lungs and brain, but viral titers were absent in the kidneys. Some untreated animals, however, had variable degrees of kidney proximal tubular injury as shown by attenuation of the proximal tubular brush border and increased NGAL and TUNEL staining. Viral titers in the lung and brain were reduced or nondetectable in mice that received ACE2-1-618-DDC-ABD, and the animals developed only moderate disease as assessed by a near-normal clinical score, minimal weight loss, and improved lung and kidney injury. This study demonstrates the preclinical efficacy of a novel soluble ACE2 protein, termed ACE2-1-618-DDC-ABD, in a lethal mouse model of SARS-CoV-2 infection that develops severe lung injury and variable degrees of moderate kidney proximal tubular injury.

Diagnostic Accuracy of CT-Scan Chest in Distinguishing Ground-Glass Opacities from Covid-19 Causes and Other Causes of Ground-Glass Opacities

Introduction: Evaluation of the effectiveness of diagnostic computed tomography of the chest in differentiating between coronavirus 2019 (COVID-19) ground glass opacities and other reasons of ground glass opacities (GGO) not related to COVID-19. Place and Duration: In the department of Radiology, Miangul Abdul Haq Jahenzeb Kidney Hospital Swat for six-months duration from March 2021 to August 2021. Methods: 90 total covid-19 confirmed patients by RT-PCR having GGO (53 males and 37 females, with 47.20 ± 15.10 years mean age) and 110 patients (63 males and 47 males) who were confirmed GGO on chest CT but not due to Covid-19 were selected for the study. The experienced radiologists studied all chest CT scans after removing all descriptive information from the images. They tested negative or positive for COVID-19 and noted other features of CT of the lungs, including laterality, distribution pattern and lobe involvement. The laboratory results and clinical data were documented. Results: This study consisted of 90 COVID19 patients and 100 non-COVID-19 with ground glass opacities on CT chest. In terms of age; no statistically significant alteration was noted amid the 2 groups (p-value = 0.129). Non-COVID-19 cases with GGO; 6 patients have atypical bacterial pneumonia, 42 patients have GGO after viral pneumonia, 14 patients have interstitial pneumonia, 5 patients have PJP, eosinophilic pneumonia in 3 patients, 9 patients have hypersensitivity pneumonia, 6 patients have drug-induced lung injury, 5 patients have pulmonary alveolar hemorrhage and pulmonary edema in 11 patients (cardiogenic and noncardiogenic). Conclusion: Chest CT is rational for distinguishing ground glass opacities form COVID-19 and non-COVID-19 reasons, with less specificity for distinguishing COVID-19 from viral pneumonia and intermediate specificity for distinguishing COVID-19 from other reasons of ground glass opacities. Keywords: SARS-COV2, COVID-19, Diagnosis, Computed tomography and ground glass opacities.

A national, multi-center study in Germany to assess implementation of infusion management, treatment satisfaction and quality of life in MS patients receiving alemtuzumab

BackgroundAlemtuzumab is an anti-CD52 antibody approved for the treatment of relapsing remitting multiple sclerosis (RRMS). The summary of product characteristics (SmPC) provides recommendations on the administration of alemtuzumab to prevent or reduce the risk of serious side effects associated with alemtuzumab infusion, including myocardial ischemia, hemorrhagic stroke, arterial dissection, and pulmonary alveolar hemorrhage. However, real-world implementation of alemtuzumab infusion management recommendations has not been previously assessed. MethodsHere we provide a large-scale multi-center (in- and outpatient) observational study on alemtuzumab infusion management in daily clinical care in Germany (ALEMLL08025; INFUSE-MS; NIS-no. 364). Parameters of infusion management - including infusion administration, clinical and laboratory monitoring - were assessed, compared between study centers and the occurrence of infusion-associated reactions (IARs) was documented. Moreover, the TSQM and MSIS-29 questionnaires were used to quantify patient satisfaction and health-related quality of life. Results140 RRMS patients were enrolled in this study. Alemtuzumab infusion regimes (treatment course 1 and 2) were comparable between infusion sites and in accordance with recommendations by the SmPC. Standardization of infusion management was associated with a satisfactory safety profile. IARs were usually mild, headache (13.6%), rash (10.7%), and pyrexia (6.4%) being the most common ones. TSQM and MSIS-29 scores denoted high patient satisfaction and health-related quality of life among RRMS patients treated with alemtuzumab. ConclusionIn conclusion, our results indicate that infusion management of alemtuzumab is highly standardized and in line with the SmPC. Alemtuzumab treatment and implementation of infusion management recommendations are associated with a satisfactory safety profile regarding the occurrence of IARs, a high patient satisfaction and health-related quality of life as important indicators for the quality of MS care.

Pulmonary thromboembolism and alveolar hemorrhage as initial manifestations of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs. SLE can affect the lung, the pulmonary vasculature, and the pleura. A 38-year-old female with limb pain and ecchymosis who later developed pulmonary thromboembolism and alveolar hemorrhage is presented here. Clinical, imaging, laboratory, and histopathological evidence is presented. The patient met the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) criteria for SLE. Furthermore, the patient had a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 35; thus, indicating severe disease. This case is an example of concomitant venous and arterial lung complications in an SLE patient.

The Efficacy and Safety of Caplacizumab in Japanese Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP): An Open-Label, Phase 2/3 Study

The Efficacy and Safety of Caplacizumab in Japanese Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP): An Open-Label, Phase 2/3 Study

DIFFUSE ALVEOLAR HEMORRHAGE IN A PATIENT WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME: A RARE BUT SERIOUS ENTITY

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a case of a middle-aged female diagnosed with antiphospholipid syndrome (APS) with biopsy-proven pulmonary capillaritis coming with dyspnea and hemoptysis. CASE PRESENTATION: 66 years female with a history of APS with pulmonary vasculitis, multiple hospitalizations for recurrent pneumonia presented to Emergency Department (ED) with 2 weeks of worsening dyspnea, coughing out of blood clots, & nose bleeds for a day. She denied fever, chills, chest pain, and bleeding from elsewhere. ED vitals includes oxygen saturation of 70% on room air, otherwise afebrile with stable hemodynamics. Physical exam showed diffuse wheezing & crackles over bilateral lungs. Lab revealed pancytopenia requiring blood transfusion. Serology showed persistently positive antiphospholipid antibodies (ACL, Beta 2 Glycoprotein) but negative ANA, dsDNA, C-ANCA, P-ANCA, Anti-GBM antibody, hemolysis labs with normal complement 3 & 4, and ESR/CRP markers. Chest x-ray & CT chest showed diffuse ground-glass opacities. Echo revealed EF 71-75% with pulmonary hypertension. She was admitted to the ICU and started on pulse steroid & broad-spectrum antibiotics. She underwent 4 cycles of plasmapheresis followed by mycophenolate & rituximab for vasculitis flare. After a week, she improved without further need of supplemental oxygen and was discharged with mycophenolate, rituximab & oral steroid. DISCUSSION: Diffuse alveolar hemorrhage (DAH) can be a rare but fatal (21% mortality) manifestation of APS ( a hypercoagulable condition) where antiphospholipid antibodies (aPL) mediated pulmonary endothelial injury causes RBCs to leak into the alveoli [1,2]. The patient may recurrently present with dyspnea, fever, cough, hemoptysis with diffuse ground-glass opacity in chest film and dropping hematocrit [1,2,3]. A thorough history, examination, lab/imaging studies, or sometimes biopsy may be required to diagnose the underlying etiology so that specific treatment can be directed along with supportive care. Serological work-up should include ANCA Abs, ANA, dsDNA, Anti-GBM, complement 3 & 4 levels to identify underlying systemic vasculitis and cardiac echo should exclude heart failure [1]. Patient with this condition has persistently elevated & high titer of aPL antibodies [1,2]. Persistent bloody fluid in bronchoscopy with bronchoalveolar lavage supports DAH [1,3]. Though not recommended routinely, tissue biopsy shows pulmonary capillaritis more often than microvascular thrombosis in APS [1,2]. Respiratory support, maintenance of hemodynamics, temporary avoidance of anticoagulants, exclusion of infection, and initiation of high dose systemic steroid with immunosuppressive agents with or without plasma exchange are key to the management in patients with DAH secondary to capillaritis from underlying autoimmune condition [1,2,3]. CONCLUSIONS: Though rare, DAH should be suspected in patient with APS to direct the appropriate treatment timely. REFERENCE #1: Stoots SA, Lief L, Erkan D. Clinical Insights into Diffuse Alveolar Hemorrhage in Antiphospholipid Syndrome. Curr Rheumatol Rep. 2019;21(10):56. Published 2019 Sep 6. doi:10.1007/s11926-019-0852-7 REFERENCE #2: Deane KD, West SG. Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. Semin Arthritis Rheum. 2005 Dec;35(3):154-65. doi: 10.1016/j.semarthrit.2005.05.006. PMID: 16325656. REFERENCE #3: Gertner E. Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment. J Rheumatol. 1999 Apr;26(4):805-7. PMID: 10229400. DISCLOSURES: No relevant relationships by Varun tej Gonuguntla, source=Web Response No relevant relationships by Resha Khanal, source=Web Response No relevant relationships by Sharad Oli, source=Web Response No relevant relationships by Shital Oli, source=Web Response No relevant relationships by kiran para, source=Web Response No relevant relationships by Ankur Sinha, source=Web Response No relevant relationships by husnain waseem, source=Web Response