Diffuse Alveolar Infiltrates Research Articles

E078 Long term outcomes of diffuse alveolar haemorrhage in antineutrophil cytoplasmic antibody-associated vasculitis: a single centre study

Abstract Background/Aims ANCA associated vasculitis (AAV) is a heterogeneous disease with significant mortality and morbidity. Diffuse Alveolar Hemorrhage (DAH) is a life-threatening condition and presents with hemoptysis, cough, breathlessness and respiratory failure. Studies have shown a prevalence of about 25%. This study was designed to assess the clinical features, serology, efficacy of treatment and long term outcomes in DAH patients secondary to AAV. Methods This was an observational study which included adult AAV Patients diagnosed based on Revised International Chapel Hill Consensus Conference classification criteria from January 2016 to August, 2023 after IEC approval. DAH was diagnosed based on clinical symptoms, Imaging (Diffuse alveolar infiltrates), drop in hemoglobin, hypoxia and Bronchoalveolar lavage in cases where feasible. Demographic details, clinical features, laboratory data including ANCA serology, treatment, disease activity, outcomes of patients were assessed prospectively. DAH and Non DAH groups were compared using Kruskal Wallis test for median values. Student t-test for mean values and Chi square for categorical variables were used to test association between two groups with statistical significance of P-Value <0.05. Results 133 AAV patients were included in the study. DAH was seen in 42(31.5%) patients. The mean (± SD) age of patients was 49.4(±18.9) years. Males (52.3%) were marginally higher in number then females (47.6%). Patients presented with a median of 8 weeks after AAV diagnosis. Hemoptysis (61.9%), cough (47.6%) and breathlessness(64.3%) were the presenting complaints. Renal, Sinusitis, Gastrointestinal involvement was seen in 83.3%, 61.9% and 14.2% respectively. Musculoskeletal and Ophthalmic features were seen in 33.3% each. RPRF was seen in 42.8%. c-ANCA, p-ANCA were seen in 73.8%,21.4% while Anti PR3 antibody and Anti MPO antibody were seen in 78.5%, 21.4% patients respectively. Median (IQR) BVAS score at presentation was 20(13-24) compared to 11(7-11) in Non DAH group which was statistically significant (p < 0.001). 10(23.8%) patients required ventilator support. IVIg was given in 3(7.1%), while plasmapheresis was used in 7(16.7%). Induction regimen with Cyclophosphamide was used in 73.8% and Rituximab (RTX) in 8(19%) patients. Maintenance RTX was used in 42.8% and 45.2% patients received Azathioprine. 23.8% patients relapsed and 54.6% patients were in remission. 10(23.8%) required Mechanical Ventilation. No patients were on long term oxygen therapy. 7(16.6%) patients died. Morbidity was seen in 16(38%) including CKD in 8(19%) patients. Median(IQR) duration of follow up was 10(6-24) months. Conclusion DAH is a serious manifestation of AAV and an important Rheumatological emergency. DAH was present in 31.5% with majority patients in remission. Mortality was seen in 16.6% and morbidity in 38% cases. Management with combination of Pulse steroids, Cyclophosphamide /Rituximab and Plasmapheresis is the key to better outcomes. Ventilator support may be necessary in severe cases. Timely diagnosis and aggressive management is the key to survival and prevents morbidity. Disclosure J.R. Yadavalli: None. K. Telang: None. P. Khatri: None. S. Dhuria: None. G. Ekbote: None. R. Gupta: None.

Fat embolism syndrome after humerus and pelvis fracture complicated by acute kidney injury requiring blood purification: a case report and literature review

BackgroundFat embolism syndrome (FES) is a rare syndrome that typically occurs 12–72 h after long bone or pelvic fractures with a classic triad of respiratory distress, neurologic changes, and petechial rash. Although Gurd’s criteria for FES include anuria or oliguria, the mechanism of acute kidney injury (AKI) remain unknown. Here, we present a case of FES complicated by AKI that required blood purification.Case presentationA 79-year-old woman was admitted to our hospital because of a right humerus and pelvic fracture caused by a traffic accident. On the second day of hospitalization, she developed impaired consciousness, respiratory failure, and disseminated intravascular coagulation (DIC). Chest radiography revealed bilateral diffuse alveolar infiltration. Brain magnetic resonance imaging revealed diffuse high signal intensity on diffusion-weighted imaging and diffuse low signal intensity on susceptibility-weighted imaging in the cerebral and cerebellar regions. The diagnosis of FES was confirmed and the patient was treated with methylprednisolone (40 mg/day) and ulinastatin. On the third day of hospitalization, she was admitted to our department because of AKI with oliguria. Although echocardiography showed an elevated right ventricular artery systolic pressure suggestive of pulmonary hypertension (PH), pulmonary congestion was initially considered on chest imaging, and hemodialysis and rapid ultrafiltration were initiated. However, she developed hypovolemic shock and treatment was switched to continuous hemodiafiltration and slow ultrafiltration. Thereafter, her consciousness, hypoxemia, DIC and PH completely improved. She was weaned from blood purification therapy on the 29th day of hospitalization. She had hemolytic anemia that might have been caused by thrombotic microangiopathy (TMA), but it resolved without plasmapheresis. On the 51st day of hospitalization, the patient was transferred to another hospital for rehabilitation.ConclusionsFES can be complicated by AKI. In this case, DIC, which was difficult to differentiate from TMA, and/or renal congestion were considered to be a cause of AKI. Chest radiographs of FES may be indistinguishable from pulmonary congestion. In our case, chest radiography showed bilateral diffuse alveolar infiltrates which was not indicative of pulmonary congestion but pulmonary involvement of FES. FES is associated with PH, which may lead to right heart failure. Therefore, the patient could have developed hypovolemic shock due to hemodialysis and rapid ultrafiltration. Clinicians should pay attention to the hemodynamics when blood purification for FES is performed.

Idiopathic pulmonary hemosiderosis and stroke secondary to protein C deficiency in a child with Down syndrome: a case report

BackgroundPatients with Down syndrome are at a higher risk of developing autoimmune disorders such as thyroiditis, diabetes, and celiac disease compared with the general population. Although some diseases are well known to be associated with Down syndrome, others such as idiopathic pulmonary hemosiderosis and ischemic stroke due to protein C deficiency remain rare.Case presentationWe report a case of a 2.5-year-old Tunisian girl with Down syndrome and hypothyroiditis admitted with dyspnea, anemia, and hemiplegia. Chest X-ray showed diffuse alveolar infiltrates. Laboratory tests showed severe anemia with hemoglobin of 4.2 g/dl without hemolysis. A diagnosis of idiopathic pulmonary hemosiderosis was confirmed by bronchoalveolar lavage showing numerous hemosiderin-laden macrophages, with a Golde score of 285 confirming the diagnosis of pulmonary hemosiderosis. Concerning hemiplegia, computed tomography showed multiple cerebral hypodensities suggestive of cerebral stroke. The etiology of these lesions was related to protein C deficiency.ConclusionIdiopathic pulmonary hemosiderosis remains a severe disease, which is rarely associated with Down syndrome. The management of this disease in Down syndrome patients is difficult, especially when associated with an ischemic stroke secondary to protein C deficiency.

New Insights into the Mechanism of Immune-Mediated Tissue Injury in Yellow Fever: The Role of Immunopathological and Endothelial Alterations in the Human Lung Parenchyma.

Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- α, IFN-γ and TGF-β compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-γ and TNF-α participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-β, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease.

Granulomatosis With Polyangiitis Presenting With Diffuse Alveolar Hemorrhage: A Systematic Review.

Granulomatosis with polyangiitis (GPA) is a systemic disease that has variable clinical expression. GPA is the most common antineutrophilic cytoplasmic antibody(ANCA)-associated vasculitis (AAV). Diffuse alveolar hemorrhage (DAH) is one of the least common pulmonary manifestations in patients with GPA.DAH is clinically marked by hemoptysis, anemia, and diffuse alveolar infiltrates on imagingas well as hypoxemic respiratory failure. The diagnosis and treatment are challenging. Recommendations for ANCA-associated vasculitis, in general, are already established; however, there is a knowledge gap that addresses the association of GPA and DAH. The aim of this systematic review is to focus on the main clinical aspects and treatmentof patients with GPA who presentwith DAH. Thorough research of available literature was performed, including studies published in the last 10 years, following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) 2020 recommendations. The following databases were included: PubMed, Medline, Embase, ClinicalTrials.com, Google Scholar, and Prospero. The search terms included: [granulomatosis] AND [polyangiitis] AND [diffuse alveolar hemorrhage] OR [diffuse pulmonary hemorrhage] NOT [microscopic polyangiitis] NOT [eosinophilic granulomatosis]. NOS was used to assess the internal validity of the study in four domains, including selection, ascertainment, causality, and reporting. Our initial search identified 8989 studies. After excluding duplicated data and using our predetermined inclusion and exclusion criteria, we were able to retrieve 18 studies. Twelve out of 18 (67%) studies were case reports. Five were retrospective cohorts and one controlled trial. The average age of patients with GPA with DAH was 49.55 ± 17.54 years (18 - 76). Male individuals had a slight predominance (59%) in comparison to female individuals (41%). The hemoglobin level at the time of presentation was 8.86 mg/dL ± 1.43. The majority of patients (61.5%) reported hemoptysis. Renal involvement was present in 66.7%. Patients who required mechanical ventilation represented 61.5%. Plasmapheresis was used in 71.4%. Mortality was 20%, and gender was not associated with mortality (p = 0.822). Hemoptysis was not associated with the need for mechanical ventilation (p = 0.928). Renal impairment was not a predictor of mechanical ventilation (p = 0.207). In summary, patients with GPA and DAH were severely ill, frequently had renal impairment upon admission, and frequently required mechanical ventilation. Steroids, rituximab, and cyclophosphamide are the first-line treatment, and plasmapheresis is still in use. Eventually, extracorporeal membrane oxygenation (ECMO) can be the salvage therapy.Randomized controlled clinical trials (RCTs) are needed to address the best therapeutic options for this population.

Protocolo diagnóstico del síndrome de hemorragia alveolar

Various diseases can produce alveolar hemorrhage, a condition which, in its acute form, can threaten the patient's life. It tends to progress with hemoptysis (although it can be absent in one-third of patients), acute anemia, and diffuse alveolar infiltrates together with acute respiratory failure. Its diagnosis is a challenge which generally requires performing bronchoalveolar lavage on a fibrobronchoscopy. The clinical progress is variable and it tends to require immunosuppressive treatment.

COVID-19-Related ARDS: Key Mechanistic Features and Treatments.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis and fluid-filled alveoli. Coronavirus disease 19 (COVID-19)-associated ARDS (C-ARDS) is a novel etiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may present with distinct clinical features as a result of the viral pathobiology unique to SARS-CoV-2. In particular, severe injury to the pulmonary vascular endothelium, accompanied by the presence of diffuse microthrombi in the pulmonary microcirculation, can lead to a clinical presentation in which the severity of impaired gas exchange becomes uncoupled from lung capacity and respiratory mechanics. The purpose of this review is to highlight the key mechanistic features of C-ARDS and to discuss the implications these features have on its treatment. In some patients with C-ARDS, rigid adherence to guidelines derived from clinical trials in the pre-COVID era may not be appropriate.

Vascular Endothelial Glycocalyx Damage and Potential Targeted Therapy in COVID-19.

COVID-19 is a highly infectious respiratory disease caused by a new coronavirus known as SARS-CoV-2. COVID-19 is characterized by progressive respiratory failure resulting from diffuse alveolar damage, inflammatory infiltrates, endotheliitis, and pulmonary and systemic coagulopathy forming obstructive microthrombi with multi-organ dysfunction, indicating that endothelial cells (ECs) play a central role in the pathogenesis of COVID-19. The glycocalyx is defined as a complex gel-like layer of glycosylated lipid–protein mixtures, which surrounds all living cells and acts as a buffer between the cell and the extracellular matrix. The endothelial glycocalyx layer (EGL) plays an important role in vascular homeostasis via regulating vascular permeability, cell adhesion, mechanosensing for hemodynamic shear stresses, and antithrombotic and anti-inflammatory functions. Here, we review the new findings that described EGL damage in ARDS, coagulopathy, and the multisystem inflammatory disease associated with COVID-19. Mechanistically, the inflammatory mediators, reactive oxygen species (ROS), matrix metalloproteases (MMPs), the glycocalyx fragments, and the viral proteins may contribute to endothelial glycocalyx damage in COVID-19. In addition, the potential therapeutic strategies targeting the EGL for the treatment of severe COVID-19 are summarized and discussed.

Diffuse Alveolar Hemorrhage as a Life-Threatening Feature of Juvenile Onset Systemic Lupus Erythematosus: A Case-Based Review

Diffuse alveolar hemorrhage is an uncommon but serious complication of systemic lupus erythematosus (SLE). We reported a 17-year-old boy with idiopathic thrombocytopenic purpura, who admitted with pallor and petechiae. He had Coombs positive hemolytic anemia and thrombocytopenia (hemoglobin 6.2g/dL, platelets 10,000/mm3 and lactate dehydrogenase 1024U/L), cough, tachypnea, and desaturation in the room air. Chest radiograph revealed bilateral diffuse alveolar opacities and computed tomography showed bilateral diffuse alveolar infiltrates and ground-glass opacity consistent with pulmonary hemorrhage. Anti-nuclear antibody (ANA) was 1:640 with positive Ro and anti-phospholipid antibodies, low C3 and C4, but negative anti-double-stranded DNA. He was treated with pulse methylprednisolone followed by tapering doses of steroids and with 6 doses of intravenous cyclophosphamide once every two weeks followed by mycophenolate mofetil. He had no relapse in the following 3 years. The case was reported to emphasise this life-threatening complication of juvenile-onset SLE and we reviewed the literature.

Acute Respiratory Distress Syndrome and COVID-19: A Literature Review.

Acute respiratory distress syndrome (ARDS) is an overwhelming inflammatory disorder of the lung due to direct and indirect insults to the lungs. ARDS is characterized by increased vascular permeability, protein-rich edema, diffuse alveolar infiltrate, and loss of aerated lung tissue, leading to decreased lung compliance, tachypnea, and severe hypoxemia. COVID-19 is generally associated with ARDS, and it has gained prime importance since it started. The mortality rate is alarmingly high in COVID-19-related ARDS patients regardless of advances in mechanical ventilation. Several pharmacological agents, including corticosteroids, nitric oxide, neuromuscular blocker, anti-TNF, statins, and exogenous surfactant, have been studied and some are under investigation, like ketoconazole, lisofylline, N-acetylcysteine, prostaglandins, prostacyclin, and fish oil. The purpose of this review is to appraise the understanding of the pathophysiology of ARDS, biomarkers, and clinical trials of pharmacological therapies of ARDS and COVID-19-related ARDS.

A RARE CASE OF PAUCI-IMMUNE PULMONARY CAPILLARITIS WITH PERIPHERAL EOSINOPHILIA

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a syndrome classically presenting with hemoptysis, diffuse alveolar infiltrates, and acute respiratory failure. It is usually associated with systemic vasculitis and auto-antibodies. Idiopathic pauci-immune pulmonary capillaritis (IPPC) is a rare form of isolated DAH that presents without other clinical features of systemic vasculitis or circulating auto-antibodies. We present a patient with DAH from IPPC, who was also found to have peripheral eosinophilia. CASE PRESENTATION: 76-year-old female presented with subacute complaint of generalized weakness and confusion. Her past medical history was significant for multiple sclerosis treated with rituximab. Initial vital signs were afebrile, BP 126/66, HR 78, RR 22, saturating 95% on 1 liter nasal cannula. Physical examination findings were significant for a markedly obese woman, decreased breath sounds and crackles noted in both lung bases, 3+ edema in both lower extremities. Laboratory workup revealed a WBC count of 7.9/µL with 30% eosinophils, hemoglobin 10 g/dL and platelets 84K. Urinalysis was consistent with urinary tract infection (UTI). Chest x-ray revealed a right basilar infiltrate and effusion, small left basilar infiltrate, pulmonary venous congestion and mild cardiomegaly. She was started on an antibiotic for UTI and a diuretic for preliminary diagnosis of heart failure. Despite diuretics, her oxygen requirements continued to increase. CT chest showed bilateral infiltrates and extensive bilateral ground glass changes. Infectious and auto-immune workup were negative. Bronchoscopy showed progressive bloody return on sequential lavage consistent with DAH. Cytology of the bronchial lavage (BAL) fluid was negative for malignancy and did not show any organisms or eosinophilia. She was treated with steroids and plasmapheresis. DISCUSSION: The differential diagnosis for DAH is broad, but mostly consists of various underlying systemic diseases, none of which our patient manifested with despite extensive work-up. The remaining practical diagnosis of exclusion was IPPC. Furthermore, her presentation included eosinophilia, although she did not appear to manifest with any of the common differentials for peripheral eosinophilia. Her presentation was not consistent with disorders such as acute eosinophilic pneumonia or acute interstitial pneumonia as her BAL did not reveal eosinophilia or neutrophilia, respectively. This may have been confounded by steroid treatment. It remains possible that her initial peripheral eosinophilia was due to an unrelated process from her pulmonary disease. CONCLUSIONS: Our patient manifested with pauci-immune pulmonary capillaritis. Our case also demonstrates concurrent peripheral eosinophilia which has not been previously described in this already rare disease. Further studies are needed to understand the pathogenesis of IPPC. REFERENCE #1: Park MS. Diffuse alveolar hemorrhage. Tuberc Respir Dis (Seoul). 2013;74(4):151-162. doi:10.4046/trd.2013.74.4.151 REFERENCE #2: Jason S. Oh, Uni Wong, Divyansh Bajaj, Stella E. Hines, "Isolated Pauci-Immune Pulmonary Capillaritis Associated with Hydrocarbon Inhalation and Marijuana Smoking: An Unusual Case of Severe Hypoxemia", Case Reports in Pulmonology, vol. 2020, Article ID 1264859, 5 pages, 2020. https://doi.org/10.1155/2020/1264859 DISCLOSURES: No relevant relationships by Joseph Bahgat, source=Web Response No relevant relationships by Frantz Hastrup, source=Web Response

DIFFUSE ALVEOLAR HEMORRHAGE: A RARE COMPLICATION OF ACUTE MYELOID LEUKEMIA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary syndrome affecting individuals with hematologic malignancies with increased incidence post bone marrow transplant. We present a rare case of DAH presumably related to pulmonary leukemic infiltration (PLI) in a newly diagnosed Acute Myelogenous Leukemia (AML) patient. CASE PRESENTATION: A 55-year-old female, previously healthy, presented to the emergency room with a 1-week history of dyspnea, cough, and epistaxis. Laboratory data were relevant for leukocytosis (WBC 150,000/mm3) with 84% blasts, thrombocytopenia (platelets 15,000/mm3), and anemia (Hb 8.9 g/dL). CT angiography of the chest was negative for pulmonary embolism but showed scattered bilateral ground-glass opacities (GGO). Peripheral blood flow cytometry revealed AML. She underwent leukapheresis with an appropriate response. On day 5 of admission, she was transferred to the intensive care unit for increased oxygen requirement and required endotracheal intubation the day after. Chest CT showed significant worsening in bilateral GGO and septal thickening. WBC 27,000/mm3, Hb 7.7 g/dL, and platelets 50,000/mm3. Bronchoscopy with serial bronchoalveolar lavages (BAL) showed an increasingly bloody return. BAL cell differential was significant for 75% blasts. She was treated with platelet transfusion, nebulized tranexamic acid, high dose corticosteroids, and empiric antibiotic therapy. Emergent induction chemotherapy (daunorubicin + cytarabine) was started. Repeat bronchoscopy in 48h showed resolution of DAH and undetectable blasts in BAL. She was extubated on day 7 post-intubation, and her respiratory status improved back to baseline. DISCUSSION: Pulmonary opacities in leukemia may be the result of an infectious process, pulmonary edema, drug toxicity, diffuse alveolar hemorrhage, intravascular leukostasis, or pulmonary leukemic infiltrates. Though the timing of pulmonary complications, clinical presentation, and chest CT findings may help identify the etiology, diagnosis is frequently challenging, and early BAL may be of benefit. In this patient, worsening respiratory status and pulmonary infiltrates despite leukapheresis excluded leukostasis and suggested PLI. Hemoptysis is absent in more than one-third of patients with DAH. She had no hemoptysis, and DAH was subsequently diagnosed with bronchoscopy. We believe that early diagnosis of PLI, excellent response to induction chemotherapy, along with other supportive measures led to a favorable outcome. CONCLUSIONS: Early recognition of acute respiratory failure etiology in patients with leukemia and pulmonary infiltrates is essential. Albeit rare, DAH should always be on the differential as early identification and treatment can likely improve outcomes. REFERENCE #1: Nanjappa S, Jeong DK, Muddaraju M, Jeong K, Hill ED, Greene JN. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia. Cancer Control. 2016 Jul;23(3):272-7 REFERENCE #2: Nucci M, Nouér SA, Anaissie E. Distinguishing the Causes of Pulmonary Infiltrates in Patients with Acute Leukemia. Clin Lymphoma Myeloma Leuk. 2015 Jun;15 Suppl: S98-103. DISCLOSURES: No relevant relationships by Tony Abdo, source=Web Response No relevant relationships by Samiksha Gupta, source=Web Response No relevant relationships by SYED HUSSAIN, source=Web Response No relevant relationships by Miloni Parmar, source=Web Response

Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters.

The effect of low environmental temperature on viral shedding and disease severity of Coronavirus Disease 2019 (COVID-19) is uncertain. We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21°C), low (12-15°C), and high (30-33°C) temperature after challenge by 105 plaque-forming units of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The nasal turbinate, trachea, and lung viral load and live virus titer were significantly higher (~0.5-log10 gene copies/β-actin, P < .05) in the low-temperature group at 7 days postinfection (dpi). The low-temperature group also demonstrated significantly higher level of tumor necrosis factor-α, interferon-γ (IFN-γ), interleukin-1β, and C-C motif chemokine ligand 3, and lower level of the antiviral IFN-α in lung tissues at 4 dpi than the other 2 groups. Their lungs were grossly and diffusely hemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7 dpi, the low-temperature group still showed persistent and severe alveolar inflammation and hemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low-temperature group were significantly higher than those of the other two groups from 10 to 17 dpi by about 0.5-1.0 log10 gene copies/β-actin. The mean neutralizing antibody titer of the low-temperature group was significantly (P < .05) lower than that of the room temperature group at 7 dpi and 30 dpi. This study provided in vivo evidence that low environmental temperature exacerbated the degree of virus shedding, disease severity, and tissue proinflammatory cytokines/chemokines expression, and suppressed the neutralizing antibody response of SARS-CoV-2-infected hamsters. Keeping warm in winter may reduce the severity of COVID-19.

A COVID-19-association-dependent categorization of death causes in 100 autopsy cases

From March through December 2020, 100 autopsies were performed (Semmelweis University, Budapest, Hungary), with chart review, of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrated by real-time reverse-transcription polymerase chain reaction testing (mean age, 74.73 years, range 40–102 years; 50 males, mean age 71.96 years, and 50 females, mean age 77.5 years). Classified by the date of death, 21 cases were from the pandemic’s “first wave” (March through July) and 79 from the “second wave” (August through December). Three mortality categories were defined by relevance of SARS-CoV-2 infection: (1) “strong” association (n=57), in which COVID-19 was primary responsible for death; (2) “contributive” association (n=27), in which a pre-existing condition independent of COVID-19 was primary responsible for death, albeit with substantial COVID-19 co-morbidity; (3) “weak” association (n=16), in which COVID-19 was minimally or not at all responsible for death. Distributions among categories differed between the first wave, in which the “contributive” association cases dominated (strong: 24%, contributive: 48%, weak: 28%), and the second wave, in which the “strong” association cases dominated (strong: 66%, contributive: 21%, weak: 13%). Charted co-morbidities included hypertension (85 %), cardiovascular diseases (71 %), diabetes (40 %), cerebrovascular diseases (31 %), chronic respiratory diseases (30 %), malignant tumors (20 %), renal diseases (19 %), diseases of the central nervous system (15 %), and liver diseases (6 %). Autopsy evaluation analyzed alterations on macroscopy as well as findings on microscopy of scanned and scored sections of formalin-fixed, paraffin-embedded tissue samples (50–80 blocks/case). Severity of histological abnormalities in the lung differed significantly between “strong” and “contributive” (p<0.0001) and between “strong” and “weak” categories (p<0.0001). Abnormalities included diffuse alveolar damage, macrophage infiltration, and vascular and alveolar fibrin aggregates (lung), with macro- and microvascular thrombi and thromboemboli (lung, kidney, liver). In conclusion, autopsies clarified in what extent COVID-19 was responsible for death, demonstrated the pathological background of clinical signs and symptoms, and identified organ alterations that led to the death. Clinicopathologic correlation, with conference discussions of severity of co-morbidities and of direct pathological signs of disease, permitted accurate categorization of cause of death and COVID-19 association as “strong,” “contributive,” or “weak.” Lung involvement, with reduced ventilatory capacity, was the primary cause of death in the “strong” and “contributive” categories. Shifts in distribution among categories, with “strong” association between COVID-19 and death dominating in the second wave, may reflect improved clinical management of COVID-19 as expertise grew.

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? COMMENTARY.

“To plasmapherese (PLEX) or not to PLEX” is a question in the induction therapy for patients with ANCA-associated vasculitis (1). Drs. Glassock and Derebail present differing yet sometimes overlapping conclusions to this question in their virtual debate. Their erudite analysis carefully examines the available literature from their respective pro or con positions. To focus the issues, let us consider three real-life patients who illustrate the quandary of when, or whether, PLEX should be used. A 32-year-old mother of three is coughing up blood in the emergency room, complaining of worsening fatigue over the past 3 weeks. Physical examination 7 months prior was unremarkable; hemoglobin was 12.8 mg/dl, and serum creatinine was 0.7 mg/dl. Urinalysis was not performed. She describes new, dark, “tea-colored” urine over the past 2 days. Urinalysis shows numerous red blood cells and red cell casts. Kidney biopsy reveals pauci-immune necrotizing and crescentic glomerulonephritis (GN) with necrosis and crescents in three of seven glomeruli. There is minimal or no interstitial infiltrate, fibrosis, or tubular atrophy. Myeloperoxidase (MPO) ANCA is positive at a titer of 93 (normal <20). High-resolution chest computed tomography reveals diffuse alveolar infiltrates with minimal bronchial abnormalities involving multiple lung lobes. Oxygen saturation is 88% on 2 L of oxygen. The diagnosis is MPO ANCA with diffuse alveolar hemorrhage and necrotizing and crescentic GN. In addition to glucocorticoids and intravenous cyclophosphamide/rituximab, would you order plasmapheresis? Dr. Derebail would argue that this patient should receive plasmapheresis. Dr. Glassock specifies that no randomized, controlled trials of PLEX as therapy for diffuse alveolar hemorrhage are available and concludes that “PEXIVAS is not very informative regarding the utility of PLEX …

Microscopic polyangiitis associated with coronavirus disease-2019 (COVID-19) infection in an elderly male

BackgroundMicroscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that affects predominantly small- sized vessels. A causal relationship between viral infections and vasculitis has been postulated.Aim of the workTo present the concomitant association of coronavirus disease 2019 (COVID-19) infection with MPA in an elderly Iranian male. Case presentationA 67 year old Iranian man with the history of COVID-19 infection and a positive polymerized chain reaction (PCR) test four weeks before admission to the neurology department with acute onset pain, numbness and progressive weakness in both hands grip, sudden left foot drop and paresthesia. Erythrocyte sedimentation rate (ESR) was 95 mm/hr, ferritin 912 ng/ml and C-reactive protein (CRP) positive, proteinuria 1.1 g/24 h and markedly elevated perinuclear (P-ANCA): 526 IU/ml. Diagnosis of MPA was held presenting with mononeuritis multiplex, glomerulonephritis followed by diffuse alveolar hemorrhage and infiltration of lymphocytes in muscle fibers and vessels wall in sural nerve biopsy. He was successfully treated by methylprednisolone (1 g/day for 3 days) followed by 1 mg/kg with gradual tapering along with cyclophosphamide (CYC) (2 mg/kg). Intravenous immunoglobulin (IVIG, 2 g/kg in four divided doses) started for the management of inflammatory mononeuritis multiplex with gradual improvement. During hospitalization, plasmapheresis was performed due to alveolar hemorrhage for 5 day. The patient returned home on day 32 and followed-up in the rheumatology clinic with improvement of muscle power and handgrip strength. ConclusionVasculitis is potentially one of COVID-19′s presenting symptoms and prompt diagnosis and treatment is crucial in improving outcome of patients.

Articles That May Change Your Practice: Current Evidence for Coronavirus Disease 2019 Therapies

Articles That May Change Your Practice: Current Evidence for Coronavirus Disease 2019 Therapies

Acute lung injury - from pathophysiology to treatment.

Acute lung injury is characterized by acute respiratory insufficiency with tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates on chest X-ray. The 1994 American-European Consensus Conference defined "acute respiratory distress syndrome, ARDS" by acute onset after a known trigger, severe hypoxemia defined by PaO2/FiO2</=200 mm Hg, bilateral infiltrates on chest X-ray, and absence of cardiogenic edema. Milder form of the syndrome with PaO2/FiO2 between 200-300 mm Hg was named "acute lung injury, ALI". Berlin Classification in 2012 defined three categories of ARDS according to hypoxemia (mild, moderate, and severe), and the term "acute lung injury" was assigned for general description or for animal models. ALI/ARDS can originate from direct lung triggers such as pneumonia or aspiration, or from extrapulmonary reasons such as sepsis or trauma. Despite growing understanding the ARDS pathophysiology, efficacy of standard treatments, such as lung protective ventilation, prone positioning, and neuromuscular blockers, is often limited. However, there is an increasing evidence that direct and indirect forms of ARDS may differ not only in the manifestations of alterations, but also in the response to treatment. Thus, individualized treatment according to ARDS subtypes may enhance the efficacy of given treatment and improve the survival of patients.

COVID-19 in a child with down syndrome and extensive pulmonary tuberculosis: a case report

Abstract Introduction: although pediatric patients have comparatively fewer cases of COVID-19, children with Down Syndrome exhibit comorbidities such as immunodeficiency, diabetes and, in this perspective, are considered a population at risk for severe COVID-19. In addition, the literature also points to an unfavorable perspective on co-infection with Mycobacterium tuberculosis, considered an important comorbidity and a predictor of a worse clinical outcome. Description: female child, nine years old, with Down Syndrome, congenital heart disease and prematurity, with significant weight loss and intermittent fever for six months. A week ago, she had an intensification of fever, productive cough and mild respiratory distress. RT-PCR for SARS-CoV-2 detectable in nasopharynx swab, chest X-ray with diffuse alveolar infiltrate, chest CT with consolidations, excavation, solid micronodules in a sprouting tree pattern mainly in the right upper and lower lobes. Molecular rapid test for Mycobacterium tuberculosis detectable in gastric lavage. After specific treatment, the patient progressed well and was discharged from the hospital after 72 hours without fever and improvement in her breathing pattern. Discussion: despite the extensive pulmonary involvement, the patient did not require invasive ventilatory support and presented a satisfactory short-term outcome. Therefore, the relevance of the association of Tuberculosis and COVID-19 and other comorbidities in the pediatric age group still remains uncertain.

Be aware of misdiagnosis tied to COVID-19 focusing: a case report of abciximab-induced alveolar haemorrhage thought to be SARS-CoV-2 in a patient with ST-segment elevation myocardial infarction.

BackgroundEarly diagnosis of diffuse alveolar haemorrhage (DAH) can be extremely difficult, as the common clinical picture is often attributed to more common clinical conditions. High degree of suspicion is key to diagnosis which can be much more difficult during the coronavirus disease 2019 (COVID-19) pandemic.Case summaryA 61-year-old man with inferolateral ST-segment elevation myocardial infarction treated by a stent to the left circumflex artery and intravenous abciximab treatment was started for the high thrombus burden. Two hours later, the patient developed dyspnoea and hypoxaemia. Chest examination revealed diffuse rales over both lung fields. Chest X-ray revealed bilateral diffuse alveolar infiltrates, while the echocardiography was normal. Chest computed tomography (CT) was performed and the ‘crazy paving appearance’, which is the typical radiological finding of COVID-19, was reported. The patient was considered to be suspected of COVID-19 and was transferred to a quarantine unit. Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) test was obtained and azithromycin and hydroxychloroquine were initiated. 48 h later, 2.6 mmol/L reduction was observed in haemoglobin levels and haemoptysis was developed. After the second negative RT-PCR with an interval of 24 h, CT was repeated and the patient was diagnosed to have abciximab-induced DAH. The patient was later followed up conventionally and discharged after two weeks without additional complications.DiscussionDAH and COVID-19 might share common clinical and radiological findings during examination. The physicians must be aware of the high motivation of the COVID-19 pandemic which can lead to misdiagnosis by overlooking other important clinical conditions.