Intra-alveolar Hemorrhage Research Articles

Risk factors for local tumor progression after RFA of pulmonary metastases: a matched case-control study.

Curative treatment of oligometastatic pulmonary disease aims at eradication of all metastases. Radiofrequency ablation (RFA) has been shown to be an efficient method and the frequency of local tumor progression (LTP) should be minimized. The objective of this study was to determine the morphological and treatment-related risk factors for LTP after RFA of pulmonary metastases. All patients treated with RFA for pulmonary metastases from 2002 to 2014 were reviewed. All LTPs from 2011 to 2014 were individually matched on the basis of tumor size, number, and histology. In total, 48 LTPs and 112 controls were blindly analyzed for morphological factors including vicinity of bronchus and vessels as well as treatment-related factors such as the size of the ablation zone and ablation margins. In the simple regression analysis, the significant predictive variables were ≤ 5-mm distance to a large bronchus (OR = 4.94; p = 0.0095) or large vessel (OR = 7.09; p < 0.001), minimal ablation margin (≤ 5 mm (OR = 42.67; p < 0.001), and a central-peripheral ablation offset/ablation zone size > 0.36 (OR = 13.83; p = 0.013). In the multiple regression model, only a minimal ablation margin ≤ 5 mm remained a significant risk factor for LTP. Only the minimal ablation margin remains significant in the multiple regression analysis; the other factors are presumably surrogates of an insufficient ablation margin. Improvement of lung RFA outcomes can probably be obtained by immediate post RFA evaluation of ablation margins to ensure a minimal ablation margin of at least 5 mm. • A distance < 5 mm to a bronchus or vessel of over 3 mm diameter is associated with insufficient ablation margin and thus risk factors for local tumor progression after pulmonary radiofrequency ablation. • A minimal ablation margin of > 5 mm after pulmonary RFA is associated with significantly less local tumor progression and should be looked for at the end of treatment session before needle removal in order to decrease local tumor progression. • Tumor location, pleural contact, occurrence of intra-alveolar hemorrhage, pulmonary atelectasis, and pneumothorax are not associated with an increased risk of local tumor progression.

Differential diagnoses of severe COVID-19 in tropical areas: the experience of Reunion Island.

To identify the differential diagnoses of severe COVID-19 and the distinguishing characteristics of critically ill COVID-19 patients in Reunion Island to help improve the triage and management of patients in this tropical setting. This retrospective observational study was conducted from 11 March to 4 May 2020 in the only intensive care unit (ICU) authorised to manage COVID-19 patients in Reunion Island, a French overseas department located in the Indian Ocean region. All patients with unknown COVID-19 status were tested by polymerase chain reaction (PCR) on ICU admission; those who tested negative were transferred to the COVID-19-free area of the ICU. Over the study period, 99 patients were admitted to our ICU. A total of 33 patients were hospitalised in the COVID-19 isolation ward, of whom 11 were positive for COVID-19. The main differential diagnoses of severe COVID-19 were as follows: community-acquired pneumonia, dengue, leptospirosis causing intra-alveolar haemorrhage and cardiogenic pulmonary oedema. The median age of COVID-19-positive patients was higher than that of COVID-19-negative patients (71 [58-74] vs. 54 [46-63.5] years, P=0.045). No distinguishing clinical, biological or radiological characteristics were found between the two groups of patients. All COVID-19-positive patients had recently travelled or been in contact with a recent traveller. In Reunion Island, dengue and leptospirosis are key differential diagnoses of severe COVID-19, and travel is the only distinguishing characteristic of COVID-19-positive patients. Our findings apply only to the particular context of Reunion Island at this time of the epidemic.

ANCA-negative microscopic polyangiitis with diffuse alveolar hemorrhage masquerading as congestive heart failure

BackgroundMicroscopic polyangiitis (MPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), involving small and medium sized vessels, often affecting the kidneys and lungs. Anti-neutrophil cytoplasmic antibody (ANCA) is detected in up to 90% of cases of MPA and its detection helps guide diagnosis, however cases of ANCA-negative MPA have been reported, hence definitive diagnosis relies on tissue biopsy.Case reportA 23-year-old man was evaluated for dyspnea and pleuritic chest pain, and found to have bilateral intra-alveolar opacities and hilar adenopathy. Diagnostic work up revealed positive anti-nuclear antibodies (ANA) and negative ANCA, which in the setting of a non-classical presentation, delayed diagnosis and appropriate treatment. Due to persistent symptoms and a high suspicion for autoimmune disease with pulmonary-renal syndrome, he underwent lung biopsy which revealed intra-alveolar hemorrhage and capillaritis indicative of microscopic polyangiitis (MPA). Surprisingly, kidney biopsy was not typical of classic MPA, but revealed less common features. Due to therapeutic noncompliance he was readmitted multiple times thereafter with rare complications of MPA such as acute pancreatitis and hemorrhagic pericardial effusion with tamponade.ConclusionThis case serves as an important clinical reminder to consider AAV even in those with negative ANCA serologies and a high suspicion for pulmonary-renal syndrome. It also demonstrates the high morbidity in cases of diagnostic delay and inadequate treatment.

Hughes-Stovin: A rare entity and challenging therapeutic management

Hughes Stovin is a rare disorder first described in 1959. It's usually diagnosed along Behcet disease (BD), with a High mortality rate that results from the ruptured pulmonary aneurysm. To investigate the course and spectrum of Hughes Stovin syndrome in BD and to assess the clinical and imaging features, treatment, and outcomes. A 38 year-old male, with a family history of AngioBehçet disease (brother who passed away) presented to the hospital with Hemoptysis in the context of a 1 year neglected history of genital/oral aphtae and pseudofolliculitis. CT angiography showed multiple pulmonary arterial aneurysms ( Fig. 1 ), pulmonary embolism along a right brachiocephalic vein thrombosis. A diagnosis of Hughes Stovin syndrome (HSS) associated with Behcet disease was made. Treatment was initiated with methylprednisolone IV 1 g daily for three days then discharged from hospital with prescription of Colchicine. Six months later, the patient had recurrence of his hemoptysis with a CT revealing an alveolar hemorrhage. Corticosteroid and immunosuppressant were the mainstay of therapy but the patient wasn’t compliant to treatment. 1 year later, without any follow-up meanwhile, the patient experienced chest pain and hemodynamic instability, CT revealed an increase in aneurysmal size and intraalveolar hemorrhage. The patient was immediately stabilized and an embolization of the right lower pulmonary artery was performed along immunosuppressants and corticoids. Few months later, the patient had a similar hospitalization that led to the embolization of right upper pulmonary artery with success. He is now still being monitored. HSS is a rare disease affecting mostly male patients between 12 and 40 years of age. Co-morbid conditions like Behçet disease and Hughes Stovin make medical management complicated and very challenging, as the history of this disease is unpredictable.

Features of pathological anatomy of COVID-19 according to autopsy results in the Volgograd Region

To make an assessment of morphological changes and a statistical analysis of the structure of mortality in COVID-19 on the basis of autopsy results in the Volgograd Region in 2020. The study was based on data from «The system for information on the work of the Volgograd Regional Autopsy Bureau» with a search for cases according to U07.1 code (the COVID-19 virus was identified) in January 1, 2020, to December 31, 2020, as well as on the autopsy materials of the Volgograd Regional Autopsy Bureau, and microscopic examination with photo fixation. Statistical processing was performed using the R programming language. During the above period, 1119 deaths were identified with a confirmed diagnosis of COVID-19. Anatomopathological examination of the autopsy material showed that 77.54% of cases had blood clots mainly in the vessels of the pulmonary microvasculature, often only in the single veins during the applied anticoagulant therapy. Thus, this investigation has revealed that the high frequency of thrombosis detected in the presence of perivascular and intra-alveolar diapedesis hemorrhages in COVID-19 confirms the tendency of patients with a severe course of the disease to manifest hemostatic disorders, significant blood vascular endothelial injury, and obvious vascular impermeability.

Fulminant Leptospirosis Leading to Shock Lung &amp; Severe Coagulopathy in a Pregnant Patient: A Case Report and Review of the Literature

Background: Leptospirosis is a zoonotic disease with high prevalence in Sri Lanka predominantly in paddy cultivat­ing areas. Severe leptospirosis is rarely described in pregnancy and there is a scarcity of data regarding its effect on pregnant patients. Acute lung injury has been recognized as the commonest fatal complication of leptospirosis. We report a case of delayed presentation of fulminant leptospirosis in a pregnant patient complicated with acute respi­ratory distress syndrome (ARDS) and severe coagulopathy resulting in death despite the optimum medical care.Case Presentation: A-31-year-old woman in the twelfth-week of pregnancy admitted with a subacute history of frequent vomiting, dry cough, watery stools, vaginal spotting, hemoptysis, and progressive shortness of breath. She had tachycardia, hypotension, and acute severe respiratory distress with high-grade fever on admission. Her inflammatory markers were high with evidence of severe coagulopathy. With worsening clinical and biochemical parameters despite intensive medical intervention, patient had a fatal outcome. The autopsy revealed shock lung with multiple intra-alveolar hemorrhages. The serum Leptospira microscopic agglutination test (MAT) was positive confirming the fulminant leptospirosis.Conclusion: Prolongrespiratory symptoms; positive lung signs with acute respiratory distress can mimic the clinical picture of atypical pneumonia. Delayed presentation of ARDS limits the management options whilst increasing the risk of fatality. A high degree of suspicion is needed to diagnose leptospirosis in pregnancy.

Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study.

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group.MethodologyThis retrospective study was performed on SLE patients’ sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml).ResultsThe cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found “ambivalent” (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.ConclusionAnti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer. We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study. Thirty patients were included. The mean age was 69 ± 12years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18years; p< 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p< 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p< 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p< 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3months, 8 deaths were observed but none was related to IgAV. Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

Comparison of the СT patterns and pulmonary histology in patients with COVID-19

Aim. Compare radiological patterns of COVID-19 pneumonia with pulmonary histology in deceased patients.Materials and methods. The analysis of recent lifetime CT studies of deceased patients was performed with the identification of all existing and leading CT symptoms, including “ground glass”, “crazy paving”, consolidation, as well as the symptom complex (pattern) of organizing pneumonia. Based on the CT symptoms, we selected the target points for taking the specimens by 3-D reconstructions. At the autopsy the lungs were entirely fixed into the front and then marked on CT sections cut from 1 to 3 pieces that were placed in paraffin and processed according to the standard technique, stained with hematoxylin and eosin and fuchsin-facelina. The specimens were analyzed by identifying all available histology changes and selecting the leading one.Results. 45 targeted pieces of lung tissue were obtained from 14 deceased COVID-19 patients (7 men/ 7 women), with an average age of 77.1 ± 12.9 (49–90 years). In deceased patients with the presence of the "ground glass" symptom, in most cases (57.1%) revealed an increase in intra-alveolar cellularity, hyaline membranes, desquamation of the alveolar epithelium and infiltration of the interalveolar septum by lymphocytes, which corresponds to the exudative phase of diffuse alveolar damage (DAP). Mosaic histological changes with alternation of filled alveoli (intraalveolar edema, clusters of red blood cells, macrophages, lymphocytes) and air alveoli were detected from the areas of “crazy paving” zones. Several cases demonstrated interstitial edema and lymphoid infiltration of interalveolar partitions of different severity without their thickening. Areas of consolidation were histologically represented by extensive intraalveolar hemorrhages and / or typical zones of hemorrhagic infarcts in 45.5% of cases. Perilobular consolidation, subpleural cords, symptoms of “halo” and “reverse halo”, which we considered as part of the symptom complex of organizing pneumonia in 43% of cases, morphologically corresponded to organizing pneumonia (the proliferative phase of DAP), as well as to distelectases.Conclusion. Comparison of CT patters and post-mortem pulmonary histology in COVID-19 deceased patients demonstrated that CT symptoms and patterns correspond to certain morphological changes of different phases of DAP.

Heme on Pulmonary Malaria: Friend or Foe?

Malaria is a hemolytic disease that, in severe cases, can compromise multiple organs. Pulmonary distress is a common symptom observed in severe malaria caused by Plasmodium vivax or Plasmodium falciparum. However, biological components involved in the development of lung malaria are poorly studied. In experimental models of pulmonary malaria, it was observed that parasitized red blood cell-congested pulmonary capillaries are related to intra-alveolar hemorrhages and inflammatory cell infiltration. Thus, it is very likely that hemolysis participates in malaria-induced acute lung injury. During malaria, heme assumes different biochemical structures such as hemin and hemozoin (biocrystallized structure of heme inside Plasmodium sp.). Each heme-derived structure triggers a different biological effect: on the one hand, hemozoin found in lung tissue is responsible for the infiltration of inflammatory cells and consequent tissue injury; on the other hand, heme stimulates heme oxygenase-1 (HO-1) expression and CO production, which protect mice from severe malaria. In this review, we discuss the biological mechanism involved in the dual role of heme response in experimental malaria-induced acute lung injury.

Guidance for the management of adult patients with coronavirus disease 2019.

In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19). On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.

Clinical Characteristics, Histopathology, and Tissue Immunolocalization of Chikungunya Virus Antigen in Fatal Cases.

Death in patients with chikungunya is rare and has been associated with encephalitis, hemorrhage, and septic shock. We describe clinical, histologic, and immunohistochemical findings in individuals who died following chikungunya virus (CHIKV) infection. We identified individuals who died in Puerto Rico during 2014 following an acute illness and had CHIKV RNA detected by reverse transcriptase-polymerase chain reaction in a pre- or postmortem blood or tissue specimen. We performed histopathology and immunohistochemistry (IHC) for CHIKV antigen on tissue specimens and collected medical data via record review and family interviews. Thirty CHIKV-infected fatal cases were identified (0.8/100 000 population). The median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of 4 days (range: 1-29) after illness onset. Nearly all (93%) had at least 1 comorbidity, most frequently hypertension, diabetes, or obesity. Nine had severe comorbidities (eg, chronic heart or kidney disease, sickle cell anemia) or coinfection (eg, leptospirosis). Among 24 fatal cases with tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was most frequently detected in mesenchymal tissues and mononuclear cells including tissue macrophages, blood mononuclear cells, splenic follicular dendritic cells, and Kupffer cells. Common histopathologic findings were intra-alveolar hemorrhage and edema in the lung, chronic or acute tenosynovitis, and increased immunoblasts in the spleen. CHIKV infection likely caused fatal septic shock in 2 patients. Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations.

Structural Integrity of the Alveolar–Capillary Barrier in Cynomolgus Monkeys Challenged with Fully Virulent and Toxin-Deficient Strains of Bacillus anthracis

Inhalational anthrax, a disease caused by inhaling Bacillus anthracis spores, leads to respiratory distress, vascular leakage, high-level bacteremia, and often death within days. Anthrax lethal toxin and edema toxin, which are composed of protective antigen (PA) plus either lethal factor (LF) or edema factor (EF), respectively, play an important yet incompletely defined role in the pulmonary pathophysiology. To better understand their contribution, we examined the structural integrity of the alveolar-capillary barrier in archival formalin-fixed lungs of cynomolgus monkeys challenged with the fully virulent B. anthracis Ames wild-type strain or the isogenic toxin-deficient mutants ΔEF, ΔLF, and ΔPA. Pulmonary spore challenge with the wild-type strain caused high mortality, intra-alveolar hemorrhages, extensive alveolar septal sequestration of bacteria and neutrophils, diffuse destabilization of epithelial and endothelial junctions, increased markers of coagulation and complement activation (including tissue factor and C5a), and multifocal intra-alveolar fibrin deposition. ΔEF challenge was lethal and showed similar alveolar-capillary alterations; however, intra-alveolar hemorrhages, bacterial deposition, and markers of coagulation or complement were absent or markedly lower. In contrast, ΔLFor ΔPA challenges were nonlethal and showed no signs of alveolar bacterial deposition or alveolar-capillary changes. These findings provide evidence that lethal toxin plays a determinative role in bacterial dissemination and alveolar-capillary barrier dysfunction, and edema toxin may significantly exacerbate pulmonary pathologies in a systemic infection.

P0507ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE. ABOUT 32 CASES

Abstract Background and Aims Anti-Glomerular basement membrane disease « anti-GBM » is a rare autoimmune disease. It most often results in a rapidly progressive glomerulonephritis syndrome associated with intra-alveolar hemorrhage. The diagnostic confirmation is histological, by the demonstration of linear deposits of immunoglobulins (IgG) along the glomerular basement membrane. The aim of our study was to describe its epidemiological, clinical, biological, immunological, histological, and evolutionary characteristics and to identify the different prognostic factors for predicting patient survival and renal survival. Method It was a retrospective, descriptive and analytical study including patients over 16 years old with anti-GBM disease proved by kidney biopsy and followed up over a period of 32 years (January 1985 to July 2017), in Internal Medicine Department of Charles Nicolle Hospital of Tunis. Results We collected 32 patients with a sex ratio H/F = 1.13. The mean age at diagnosis was 42 years old with extremes of 18 to 81 years old. The most frequent extra-renal manifestations were pulmonary (53%), neurological (12.5%) and ocular (6%) manifestations. Hematuria associated with proteinuria was constantly found. The latter was nephritic in 31% of patients. All patients had renal insufficiency on admission, oligo-anuric in 60% of cases. The use of extra-renal treatment at admission was necessary in 75% of patients. On the immunological level, the search for anti-MBG antibodies, performed in 20 patients, was positive in 65% of cases. All our patients had undergone a renal biopsy puncture with direct immunofluorescence study. Diffuse extra-capillary glomerulonephritis was observed in 93% of patients. Corticotherapy was initiated in 27 cases, associated with plasma exchange in 21 cases and cyclophosphamide in 17 cases. Nine of our patients died in the first year. Renal outcome was marked by partial remission in 2 cases and end-stage renal failure in 19 cases. In univariate analysis, an age greater than 60 years and the occurrence of respiratory distress were predictors of death. Oligo-anuria and need dialysis on admission were predictive factors for progression to end-stage renal failure. Conclusion Anti-GBM disease is a serious illness. Current therapeutic modalities have significantly improved patient survival. These must be intensive and rapid in order to hope for a favorable renal evolution whose prognosis remains reserved.

Upregulation of Intragraft Inflammatory Cytokine is Associated with Pulmonary Allograft Rejection in MHC-Inbred CLAWN Miniature Swine

A close link between early initiation of ischemia-reperfusion injury and subsequent immune system activation is well recognized in several organ transplants, however, large animal models to investigate the role of innate immunity in transplant tolerance and rejection have been still limited. In this study, we evaluated the association of intragraft inflammatory change and pulmonary allograft rejection using DNA-PCR typed MHC-inbred CLAWN miniature swine. As Group 1, six swine received fully MHC-mismatched lungs with 12-days of tacrolimus (35-45 ng/ml). As Group 2, three recipients were transplanted with fully MHC-mismatched lung grafts from brain-dead (BD) donors induced by subdural balloon and subsequently ventilated for 6 h before organ procurement to investigate whether BD affects the graft survival. As Group 3, the BD donor was treated with carbon monoxide (CO) for 3 hours before organ procurement, anticipating to reduce inflammatory response in the graft and then transplanted to the MHC-mismatched recipients. Graft function was assessed with blood gases drawn from the pulmonary vein of the transplanted lung and serial chest X-rays and open lung biopsy. The expression of mRNA of proinflammatory cytokines of the grafts were quantified using real-time RT-PCR. All grafts in Group 1 was rejected within 63 days (47 ± 7 days) with diffuse mononuclear infiltrates associated with intra-alveolar hemorrhage and capillary congestion, consistent with severe cellular and antibody-mediated rejection. All animals in Group 2 rejected their grafts within 35 days with accelerated development of anti-donor antibodies. CO therapy to the BD donors was dramatically effective in prolonging graft survival; all recipients accepted their grafts over 35 days (82 ± 13 vs 26 ± 5 days). PO2 of graft PV in Group 3 was significantly higher than in Group 2 (546 ± 57 vs. 349 ± 28 mmHg) associated with fewer inflammatory cell infiltrates on 2-hour and 2-day biopsies. Up-regulation of proinflammatory cytokines as early as 6h after BD induction were markedly reduced by CO inhalation. These data clearly demonstrated that upregulation of intragraft inflammatory cytokine is associated with not only early graft function but pulmonary allograft rejection in clinically relevant large animal using MHC-inbred CLAWN miniature swine.

Protective effects of melatonin on lung damage associated with one-lung ventilation: An experimental study.

This study aims to investigate the protective effect of melatonin on lung damage induced by one-lung ventilation in a rat model. A total of 20 healthy, Sprague-Dawley male rats were randomized into two equal groups as control (n=10) and melatonin groups (n=10). The control group underwent 60 min of one-lung ventilation, followed by 30 min of two-lung ventilation. In the melatonin group, the rats were administered 10 mg/kg melatonin intraperitoneally 10 min before the start of the experiment. At the end of both ventilation periods, tissue samples were obtained from the lungs of the control and melatonin groups for biochemical analysis and histopathological examinations. Tissue superoxide dismutase, malondialdehyde, and tumor necrosis factor-alpha levels were measured. Lung tissue samples were examined based on the presence and amount of alveolar congestion, intra-alveolar bleeding, and leukocyte and lymphocyte infiltration. At the end of the study, lung tissue malondialdehyde (3.8±0.9 vs. 1.8±0.8 μM; p<0.001) and tumor necrosis factor-alpha levels (47.2±15.0 vs. 21.8±7.2 pg/mL; p<0.001) of the melatonin group were found to significantly decrease, compared to the control group. Superoxide dismutase levels of the melatonin group increased at the end of both ventilation periods, and the increase at the end of one-lung ventilation was found to be statistically significant (0.6±0.2 vs. 1.3±0.7 U/mL; p<0.05). Histopathological examination demonstrated that the tissue damage was less in the melatonin group. There was a significant decrease in the alveolar congestion in this group (p=0.0401). Although other histopathological parameters decreased in the melatonin group, no significant difference was found. Our study results demonstrate that melatonin has protective effects on the lung damage induced by one-lung ventilation both at biochemical and histopathological levels in rats.

Curcumin, an Active Constituent of Turmeric Spice: Implication in the Prevention of Lung Injury Induced by Benzo(a) Pyrene (BaP) in Rats.

Benzo(a)pyrene (BaP) is a well-known carcinogen and enhances oxidative stress and apoptosis and also alters several molecular pathways. Curcumin is an active ingredient of Curcuma longa, and it has potent anti-inflammatory, antioxidant activity that defends cells from oxidative stress and cell death. The objectives of the present study were to explore the protective effects of curcumin against long-term administration of BaP induced disturbances in lungs of rats. Male rats were randomly divided into four groups: saline control, BaP only, BaP + curcumin, and curcumin only. Lung histopathology, electron microscopy, inflammatory cytokine release, antioxidant levels, apoptosis, and cell cycle were examined. Instillation of BaP significantly increased infiltration of inflammatory cells in alveolar space and inflammatory cytokine in blood. BaP induced lung tissue alterations including mild bronchitis, scant chronic inflammatory cell infiltrate in the wall of the respiratory bronchiole, and mild intra-alveolar haemorrhage. However, these alterations were found to be significantly less as mild inflammatory cell infiltrate in curcumin plus BaP treated group. Furthermore, electron microscopy results also showed necrotic changes and broken cell membrane of Type-II epithelial cell of alveoli in BaP group, which was reduced after adding curcumin treatment. In addition, we found BaP plus curcumin treatment effectively reduced inflammatory cytokines Tumour Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) levels in blood serum. Moreover, the levels of tunnel staining and p53 expression were significantly increased by BaP, whereas these changes were noticeably modulated after curcumin treatment. BaP also interferes in normal cell cycle, which was significantly improved with curcumin treatment. Overall, our findings suggest that curcumin attenuates BaP -induced lung injury, probably through inhibiting inflammation, oxidative stress and apoptosis in lung epithelial cells, and improving cell proliferation and antioxidants level. Thus, curcumin may be an alternative therapy for improving the outcomes of Benzo(a)pyrene-induced lung injury.

Efficacy of thymoquinone in the treatment of experimental lipopolysaccharide-induced acute lung injury.

IntroductionAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are acute onset syndromes affecting the lungs, which develop for several reasons and are characterized by hypoxemia and diffuse lung infiltration. The activity of thymoquinone (TQ) is known in acute lung injury. It is considered that it could be effective in ALI/ARDS treatment by ensuring possible COX-2 inhibition.AimBy this study was to show the protective activity of TQ in lipopolysaccharide (LPS) induced acute lung injury.Material and methods: A total of 28 BALB/c male mice were randomized to 4 groups of 7 as the Control group, TQ group (3 mg/kg), LPS group (5 mg/kg) and TQ treatment group. TQ was administered intraperitoneally 1 hour before the intratracheal administration of LPS (5 mg/kg). The mice were sacrificed 6 hours after the LPS administration and the lungs were extracted for histopathological examination. All experimental procedures complied with the requirements of the Animal Care and Ethics Committee of Dokuz Eylul University.ResultsWhen all the study groups were compared, significant differences were found between the groups in terms of the degrees of neutrophil migration (p = 0.042), intra-alveolar hemorrhage (p = 0.004) and alveolar destruction (p < 0.0006). A significant recovery was observed in the lung histopathological changes (neutrophil migration, intra-alveolar hemorrhage and alveolar destruction) in the TQ treatment group.ConclusionsThe results of this study showed that TQ may have a protective effect against LPS-induced acute lung injury. The possible mechanism could be considered to be cyclooxygenase 2 (COX-2) inhibition.

Histopathological Spectrum of Lesions in Lungs on Post-mortem Specimen in a Tertiary Centre of Bastar Region- A Retrospective Study

Introduction: Lungs are the major organ involved in a number of infectious, inflammatory and occupational disease, secondarily involved in almost all form of terminal disease. So many people around the world suffer from preventable lung disease. Many a times it has been found that when gross pathology could not help to evaluate cause of death, histopathology provide the valuable information. Aim: To study the spectrum of histopathological finding in lung autopsy and the incidental findings identified during histopathological examination. Materials and Methods: This was a retrospective study done in the Department of Pathology, Lt B.R.K.M G.M.C, Bastar, Chhattisgarh, India, over a period of 10 years i.e., from January 2010 to December 2019. The study consisted of Lung specimens (474 cases) from medico-legal autopsies, irrespective of their age and sex, received during this period. Gross and Microscopic features were documented, and diagnosis was made. The results were analysed based on gross findings and the histopathological examination. Results: Among 474 cases studied during period of 10 years, maximum cases were seen in 30-39 (141 cases) years of age group. Males were more commonly affected 345 (73%) as compared to Females 129 (27%). Pathological findings of Lung were seen in 441 cases, of which Pulmonary Oedema with Congestion was found in 352 cases, along with Intra-alveolar Haemorrhage in 41 cases, Bronchopneumonia in 14 cases, Lobar Pneumonia in 11 cases, seven cases of Tuberculosis, Interstitial Pneumonia in seven cases, Vegetative material in three cases, Emphysema in three cases, Aspiration pnuemonitis in two cases and one case of Chronic Bronchitis. Conclusion: Autopsy study of lung specimens gives valuable information, improves clinical diagnosis and provides diagnostic setup for better clinical assessment. Histopathological examination proves to be the great diagnostic tool in the identification of lung lesions which were incidental finding or direct cause of death. Limitation was non-availability of large specimens, detailed clinical history and autolysis of the organ.

Veno-Venous Extra-Corporeal Membrane Oxygenation (ECMO) in a Child with Hemoptysis and Fontan Circulation

Background: Extracorporeal membrane oxygenation is a rescue life support technique used in life threatening conditions of refractory respiratory and/or cardiac distress. Indication for extracorporeal life support in children depends on age and varies from pulmonary to cardiac pathologies. In some cases, it may be used as a bridge to a therapeutic procedure. We described here the management of respiratory failure due to hemoptysis in a child with a Fontan circulation and veno-venous extracorporeal membrane oxygenation which served as a bridge to angio-embolization. Hemoptysis can be a life threatening condition which can lead to hypovolemic shock and impaired alveolar gas exchange. The latter can result in respiratory failure and consequent asphyxia. When hemoptysis occurs in a patient with a univentricular heart and a Fontan circulation, management of this clinical situation can be challenging due to the particular physiology of the latter. Total cavopulmonary connection is a palliative surgical repair which constitutes Fontan circulation as a definitive treatment in patients with a univentricular heart. Methods: Case report description of a 16 year-old boy with a univentricular heart and a Fontan circulation who presented hemoptysis managed with a veno-venous extracorporeal membrane oxygenation (ECMO) as a bridge to angio-embolization. Results: Hemoptysis due to diffuse intra-alveolar hemorrhage from collateral circulation was successfully treated in this young patient with pulmonary vascular embolization. This allowed to wean the patient from extra-corporeal membrane oxygenation. Conclusion: Veno-venous ECMO can be life-saving as a bridge to angio-embolization for severe hemoptysis in patients with Fontan circulation. The reported case allows to underline that our multidisciplinary approach in this complex pediatric patient surely participated to improve outcome.