An Unusual Etiology of Fluorodeoxyglucose Avid Intrathoracic Lymph Nodes.

A middle-aged man in his 50s, active smoker, presented to the pulmonary office for lung cancer evaluation. On a low-dose computed tomography for lung cancer screening, he was found to have an 8 mm endobronchial lesion in the right main stem bronchus. A PET-CT revealed no endobronchial lesion, but incidentally, fluorodeoxyglucose (FDG) avidity was present in the right hilar (SUV 13.2) and paratracheal lymph nodes (LNs). He underwent bronchoscopy and EBUS-TBNA of station 7 and 10 R LNs. The fine needle aspiration (FNA) revealed necrotizing epithelioid granuloma. The acid-fast bacilli (AFB) and Grocott methenamine silver (GMS) stains were negative. He had suffered from pneumonic tularemia 13 months ago and immunohistochemical staining for Francisella tularensis on FNA samples at Center for Disease Control and Prevention was negative. The intense positron emission tomography (PET) avidity was attributed to prior tularemic intrathoracic lymphadenitis without active tularemia, a rare occurrence. To the best of our knowledge, PET-positive intrathoracic lymph node beyond one year without evidence of active tularemia has not been previously reported.

A Curious Case of Clear Cell Morphology in a Patient with Lung Cancer: Diagnostic Challenges.

An 82-year-old woman with COPD presented to the emergency department with cough, increasing sputum production, wheezing, and worsening shortness of breath for two weeks. On imaging studies, the patient was found to have a right upper lobe spiculated nodule and an endobronchial lesion with near total occlusion of the right lower lobe bronchus with sub-segmental atelectasis. Bronchoscopy with EBUS-TBNA of subcarinal and right hilar lymph nodes revealed lung cancer with clear cell phenotype. Given the predominance of clear cell morphology, the diagnosis of metastatic renal or ovarian cancer was entertained. However, there was no evidence of renal or ovarian lesions on the PET-CT scan, ruling out the possibility. Salivary gland type lung cancer (STLC), which is responsible for less than 1% of all lung cancer cases in adults, was also considered. The two distinct STLCs that may have similar morphologic appearances are hyalinizing clear cell carcinoma (HCCC) and mucoepidermoid carcinoma (MEC). The other type of tumour in the lung that demonstrates a clear cell phenotype is perivascular epithelioid cell neoplasms or PEComa, which are mesenchymal in origin. Immunohistochemical staining was strongly positive for p63, CK5/6, CK7, CK-LMW, and negative for TTF-1, Napsin A, p16, and CK20. Additional staining, including HMB-45, S-100, and mucicarmine, were also negative. Next-generation sequencing for the salivary gland fusion panel, including EWSR1-ATF1 fusion and EWSR1 gene rearrangement for HCCC and MAML2 gene rearrangements for MEC, was negative. She was diagnosed with non-small cell lung cancer favouring squamous cell carcinoma with clear cell phenotype, a rare entity.

Vaping Associated Acute Eosinophilic Pneumonia: A Clinical and Radiologic Mimicker of COVID-19.

Acute eosinophilic pneumonia (AEP) is a rare cause of respiratory failure. It is primarily a disease of smokers, either a new smoker or an existing one with a recent increase in cigarette consumption. Other risk factors include toxic gas exposure, inhalational illicit drugs, and smoking marijuana. AEP has also been reported in patients with e-cigarette or vaping associated lung injury (EVALI). We present the case of a 20-year-old male who presented to the hospital with acute respiratory failure. The patient has been vaping heavily for the past three months and started smoking three days before presenting to the emergency department. He was hypertensive, tachycardic, tachypneic, and required high-flow nasal cannula to maintain SpO2 > 92%. His condition deteriorated in the first 24 hours following hospitalization requiring noninvasive positive pressure ventilation. Bronchoalveolar lavage revealed an eosinophil count of 36%. Bronchoalveolar lavage (BAL) cytology revealed lipid-laden macrophages. He was diagnosed with AEP due to EVALI, and the patient was treated with high dose corticosteroid with subsequent improvement. Before the bronchoscopic evaluation, the clinical and radiologic findings were consistent with COVID-19, and the patient was tested twice for SARS-CoV-2 PCR. In the appropriate clinical setting, AEP should be considered in the differential diagnoses of community-acquired pneumonia, acute respiratory distress syndrome (ARDS), and COVID-19, especially in this pandemic era.

Comparing the clinical characteristics and outcomes of COVID-19-associate pulmonary aspergillosis (CAPA): a systematic review and meta-analysis.

PURPOSE: Invasive pulmonary aspergillosis has been increasingly recognized in COVID-19 patients, termed COVID-19-associate pulmonary aspergillosis (CAPA). Our meta-analysis aims to assess the clinical characteristics and outcomes of patients diagnosed with CAPA compared to those without CAPA. METHODS: We searched the Pubmed, Cochrane Library, SCOPUS, and Web of Science databases for studies published between January 1, 2020 and August 1, 2021, containing comparative data of patients diagnosed with CAPA and those without CAPA. RESULTS: Eight cohort studies involving 729 critically ill COVID-19 patients with comparative data were included. CAPA patients were older (mean age 66.58 vs. 59.25 years; P = 0.007) and had underlying chronic obstructive pulmonary disease (COPD) (13.7 vs. 6.1%; OR 2.75; P = 0.05). No differences in gender, body mass index (BMI), and comorbidities of diabetes and cancer were observed. CAPA patients were more likely to receive long-term corticosteroid treatment (15.0 vs. 5.3%; OR 3.53; P = 0.03). CAPA patients had greater severity of illness based on sequential organ failure assessment (SOFA) score with a higher all-cause in-hospital mortality rate (42.6 vs. 26.5%; OR 3.39; P < 0.001) and earlier ICU admission from illness onset (mean 11.00 vs. 12.00 days; P = 0.003). ICU length of stay (LOS), invasive mechanical ventilation (IMV) duration, the requirement of inotropic support and renal replacement therapy were comparable between the two groups. CONCLUSIONS: CAPA patients are typically older with underlying COPD and received long-term corticosteroid treatment. Furthermore, CAPA is associated with higher SOFA scores, mortality, and earlier onset of ICU admission from illness onset.

Clinical Characteristics Between Survivors and Nonsurvivors of COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation (ECMO) Support: A Systematic Review and Meta-Analysis.

Background: The use of extracorporeal membrane oxygenation (ECMO) in coronavirus disease 2019 (COVID-19) for refractory respiratory failure, severe cardiac dysfunction, and bridge to lung transplantation has been steadily increasing during the ongoing global pandemic. Objective: Our meta-analysis aims to compare the clinical characteristics between COVID-19 survivors and nonsurvivors requiring ECMO support. Methods: A systematic search of Pubmed, Cochrane, Embase, Scopus, and Web of Science databases was performed between December first, 2019, to June first, 2021. Studies with comparative data of COVID-19 ECMO patients were selected, in which clinical characteristics and complications were assessed. Results: Sixteen cohort studies involving 706 COVID-19 patients requiring ECMO support with pooled mortality rate of 40% were included. Younger age (mean 51 years vs 55 years; P < .001), fewer comorbidities (23% vs 31%; odds ratio [OR] 0.55; P = .02), and less renal replacement therapy (RRT) (21% vs 39%; OR 0.41; P = .007) and vasopressor (76% vs 92%; OR 0.35; P = .008) requirement were demonstrated in COVID-19 survivors requiring ECMO support than nonsurvivors. Survivors also had higher pre-ECMO pH (mean 7.33 vs 7.26; P < .001) than nonsurvivors. No difference was observed in gender, body mass index, duration of mechanical ventilation (MV) before ECMO support initiation, total ECMO support duration, and pre-ECMO parameters of PaO2/FiO2 ratio, tidal volume (mL/kg), positive end-expiratory pressure, and plateau pressure. The rate of bleeding complications was lower in survivors (32% vs 59%; OR 0.36; P = .001) than nonsurvivors, but no difference was observed in thromboembolism and secondary infections. Conclusions: We found advanced age, multiple comorbidities, lower pre-ECMO pH, greater RRT, and vasopressor requirements, and bleeding are predictors of death in COVID-19 patients requiring ECMO support. The duration of MV before ECMO support initiation and total ECMO support duration was similar among survivors and nonsurvivors. Our study results have important clinical implications when considering ECMO support in critically ill COVID-19 patients.

Proposed Pathogenesis of Diffuse Alveolar Hemorrhage in Idiopathic Pulmonary Hemosiderosis.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease that causes diffuse alveolar hemorrhage (DAH). The latest data suggests an immunologic origin of IPH, and a new name, immune mediated pulmonary hemosiderosis (ImPH), has been proposed. However, the exact immunologic mechanism has remained elusive for nearly eight decades despite extensive research, including detailed histopathologic analysis. Although several hypotheses have been proposed to describe the pathobiology of IPH, none of them explain the clinical and histopathologic findings conclusively. In this manuscript, we have presented a new hypothesis for the pathogenesis of DAH in IPH. We hypothesize that DAH in IPH is not immunocomplex mediated but due to histamine, eosinophilic cationic protein (ECP), and possibly vascular endothelial growth factor (VEGF). These bioactive proteins induce endothelial and alveolar epithelial damage, leading to the peri-capillary and intraalveolar escape of RBCs. The deformability of the RBC likely also plays a role. The supranormal secretion of histamine, ECP and VEGF occurs in genetically predisposed individuals with an aberrant immunologic response. The histamine is released from the basophils and possibly the mast cells in response to cytokines secreted by activated lymphocytes. The lymphocyte activation occurs after exposure to a known (gluten) or unknown antigen. The same lymphocyte-derived cytokines also induce eosinophilic degranulation of ECP and VEGF in the pulmonary circulation. We believe that our hypothesis unifies the observed clinical variabilities and histopathologic findings in IPH, and we hope that would promote future research in the field of IPH.

Pneumomediastinum: A Rare Complication of Endobronchial Ultrasound Guided Fine Needle Aspiration.

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a commonly performed outpatient procedure used for the diagnosis, staging of lung cancer, and the evaluation of thoracic lymphadenopathy of unknown origin. With the advent of this minimally invasive technology, mediastinoscopy, once the gold standard, has fallen out of favour. Pneumomediastinum is a rare complication of EBUS-TBNA and can often be managed conservatively. We present a case of a 52-year-old female who developed pneumomediastinum following EBUS-TBNA and improved with expectant management in the emergency department. We discuss the proposed pathophysiology of this rare occurrence that usually follows a benign course. Severe complications, such as mediastinitis and tracheal tear, need to be excluded promptly.

Liposteroid Therapy for Idiopathic Pulmonary Hemosiderosis: A Scoping Review of the Literature.

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage (DAH). Glucocorticosteroids (CS) represent the first line therapy for IPH. Although most patients respond to CS, steroid refractoriness is seen in an appreciable minority of patients. This paper reviews and evaluates the efficacy and safety profile of liposomal dexamethasone 21-palmitate (liposteroid) for the treatment of IPH. Medline, Embase and Web of Science biomedical databases were searched between 1980 and 2020 to identify papers describing patients with IPH, who were treated with liposteroid. A total of five articles were identified. Four in the form of case reports and one as a case series. A total of 12 pediatric patients (5 boys, 7 girls) were identified, with a median age of 2.3 years (range 0.5-8.6). Liposteroid therapy in intravenous doses ranging 0.06-0.1 mg/kg body weight appeared to be effective for both remission induction therapy, and maintenance therapy. There was no mortality among patients treated with liposteroid, either in the acute phase or during follow-up. The majority of patients for whom long-term follow-up data were available, were cured or in disease remission. No acute adverse events were reported, and long-term side effects were minimal and tolerable. Liposteroid represents a potential alternative or supplement to conventional CS therapy, as it appears to be more efficacious and associated with fewer side effects. Larger prospective, controlled trials are necessary to be able to define more precisely the therapeutic role of liposteroid in IPH.

Clinical Outcomes of Routine Awake Prone Positioning in COVID-19 Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Before coronavirus disease 2019 (COVID-19) emerged, proning had been demonstrated to improve oxygenation in those with acute hypoxic respiratory failure and be performed in non-intensive care settings. This benefit was further exemplified by the COVID-19 pandemic, leading to awake prone positioning (APP). We assessed the efficacy of routine APP versus standard care in preventing death and invasive mechanical ventilation (IMV) in non-intubated hypoxic COVID-19 patients. PubMed, Cochrane Library, Scopus, and medRxiv databases were used from January 1st, 2020, to January 15th, 2022, to identify randomized controlled trials (RCTs). Routine APP group were encouraged to be self-prone, whereas the standard care group received care according to local clinical practice and allowed APP crossover as rescue therapy. We included eight COVID-19 RCTs assessing 809 APP vs. 822 standard care patients. APP group had less IMV requirement (26.5% vs. 30.9%; OR - odds ratio 0.77; P=0.03) than the standard care group, with subgroup analysis showing greater benefit (32.5% vs. 39.1%; OR 0.75; P=0.02) for those mainly requiring oxygen support of non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC). The time to IMV initiation was similar (mean 8.3 vs. 10.0 days; P=0.66) for patients requiring NIMV and HFNC. Patients mainly receiving supplemental oxygen and non-rebreather masks had improved oxygenation parameters, although not statistically significant. Other outcomes involving all-cause hospital mortality, hospital and ICU (intensive care unit) length of stay, and adverse events were comparable. APP appeared to be an important modality for reducing IMV requirements, especially in those requiring NIMV and HFNC.

Comparing the outcomes of intrapleural fibrinolytic and DNase therapy versus intrapleural fibrinolytic or DNase therapy: A systematic review and meta-analysis.

BACKGROUND: Multiple studies describing the benefits of intrapleural fibrinolytic over placebo and DNase therapy have been published, but few have been published on intrapleural fibrinolytic and DNase therapy. OBJECTIVE: Our meta-analysis aims to compare the outcomes of surgical intervention, mortality, and hospital length of stay between intrapleural fibrinolytic and DNase therapy with either intrapleural fibrinolytic or DNase therapy alone in patients with pleural space infections. METHODS: We searched Pubmed, EMBASE, Web of Science, and Cochrane library databases for observational studies and randomized controlled trials (RCTs) containing comparative data for hospitalized adults and children with pleural infections receiving intrapleural therapy of fibrinolytic and DNase versus those receiving intrapleural fibrinolytic or DNase alone. Meta-analysis was performed using the Review Manager software, and heterogeneity was tested using I2 statistics. RESULTS: A total of 2 cohorts and 2 RCTs involving 362 adult and children was included. There was significant reduction in surgical intervention requirement among patients who received intrapleural fibrinolytic and DNase (OR 0.30; 95% CI 0.11-0.83; I2 = 31%; P = 0.02) than those receiving either intrapleural fibrinolytic or DNase alone. No difference was observed for mortality (OR 0.72; 95% CI 0.31-1.71; I2 = 0%; P = 0.46) and complication rates (OR 3.09; 95% CI 0.75-12,74; I2 = 54%; P = 0.12). The hospital length of stay (mean 13.70 vs. 16.67 days; P = 0.19) and duration of chest tube drainage (mean 6.47 vs. 6.30 days; P = 0.58) was similar between the two groups. CONCLUSION: Combination of intrapleural fibrinolytic and DNase, compared to single-agent intrapleural therapy alone, is associated with a lesser need for surgical interventions. However, no difference was found in mortality, hospital length of stay, and chest tube drainage duration.

Narrative review of the relationship between COVID-19 and PJP: does it represent coinfection or colonization?

BACKGROUND: Pneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine whether the diagnosis of pneumocystis jirovecii pneumonia (PJP) in COVID-19 patients represents coinfection or colonization based on the evidence available in the literature. We also discuss the decision to treat COVID-19 patients with coinfection by PJP. METHODS: A literature search was performed through the Pubmed and Web of Science databases from inception to March 10, 2021. RESULTS: We identified 12 COVID-19 patients suspected to have PJP coinfection. All patients were critically ill and required mechanical ventilation. Many were immunosuppressed from HIV or long-term corticosteroids and other immunosuppressive agents. In both the HIV and non-HIV groups, severe lymphocytopenia was encountered with absolute lymphocyte and CD4+T cell count less than 900 and 200 cells/mm, respectively. The time to PJP diagnosis from the initial presentation was 7.8 (range 2-21) days. Serum lactate dehydrogenase and beta-D-glucan were elevated in those coinfected with PJP. All patients were treated with anti-PJP therapy, predominantly sulfamethoxazole-trimethoprim with corticosteroids. The overall mortality rate was 41.6%, and comparable for both HIV and non-HIV groups. CONCLUSION: As the current evidence is restricted to case reports, the true incidence, risk factors, and prognosis of COVID-19 patients with PJP coinfections cannot be accurately determined. Comorbidities of poorly controlled HIV with lymphocytopenia and multiple immunosuppressive therapies are likely predisposing factors for PJP coinfection.

State-of-the-art review of secondary pulmonary infections in patients with COVID-19 pneumonia.

BACKGROUND: The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. OBJECTIVE: This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. METHOD: We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. RESULTS: The incidence of secondary pulmonary infections is low at 16% (4.8-42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9-33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2-21 days) from initial hospitalization and 9 days (4-18 days) after ICU admission. The use of antibiotics is high at 60-100% involving the studies included in our review. CONCLUSION: The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.

Comparing Central Venous Blood Gas to Arterial Blood Gas and Determining Its Utility in Critically Ill Patients: Narrative Review.

Arterial blood gas (ABG) analysis is used in critical care units to determine the degree of oxygenation, adequacy of ventilation, and the presence and severity of acid-base disturbances in the body. However, arterial puncture may result in complications, and the difficulty in acquiring arterial blood may delay care. Central venous blood gas (VBG) is a potentially more accessible alternative to ABG sampling. Current evidence suggests that pH and Pco2 obtained via peripheral VBG correlate well with ABG measurement. Nevertheless, the value of using central VBG to guide clinical decisions or as a surrogate for ABG is unclear. The purpose of this review is to explore the relationship between ABGs and central VBGs in critically ill patients. We performed a MEDLINE search using the following search terms: venous blood gas, arterial blood gas, and central venous blood gas. We excluded studies that did not involve human subjects, and only pH and Pco2 values were reviewed and examined from the studies included. All cited references from included studies were also reviewed to identify relevant literature. We identified 7 studies that met our criteria. In studies of hemodynamically stable patients, the mean difference between arterial and central venous pH and Pco2 was 0.03 units and 4-6.5 mm Hg, respectively. However, in patients with circulatory failure, the difference between central venous and arterial pH/Pco2 was 4-fold greater. We concluded that central VBG parameters of pH and Pco2 are potentially good surrogates for determining arterial pH and Pco2 in a stable patient without severe acid-base disturbances. Furthermore, central VBG can be used as a useful screening tool for arterial hypercapnia. In addition, we derived an adjustment formula for ABG conversion from central VBG: (1) arterial pH = venous pH + 0.05 units and (2) arterial Pco2 = venous Pco2 - 5 mm Hg.

Diffuse Alveolar Hemorrhage in Cardiac Diseases.

Diffuse alveolar hemorrhage (DAH) is a rare condition with reported mortality ranging between 20 and 100%. There are many etiologies of DAH. Cardiac diseases are likely underreported causes of DAH. Heart failure and mitral valve diseases are the most common cardiac causes of DAH. The DAH results from pulmonary venous hypertension leading to stress failure of the pulmonary capillaries. There is also a contribution of the bronchial circulation. The Alveolar-capillary membrane or blood-gas barrier is an extremely thin structure that allows rapid and passive diffusion of oxygen from the inhaled air to the pulmonary capillaries while preventing pulmonary edema and DAH with chronic elevation of the transmural hydrostatic pressure. The purpose of this manuscript is to inform the clinician about this rare cause of DAH, which may be overlooked unless specifically sought after. We also discuss the pathophysiologic aspects of DAH and the safety mechanisms in place to prevent such occurrences.

Short Review of Liposteroid: A Novel Targeted Glucocorticoid Preparation for Treatment of Autoimmune and Inflammatory Diseases.

This paper briefly reviews the safety and efficacy of liposteroid in different inflammatory and non-inflammatory diseases. Corticosteroids (CS) are the first-line therapy in many inflammatory and autoimmune disorders. Although highly efficacious, long-term use of CS is limited due to the occurrence of significant side effects. Liposteroid, which is a liposomal formulation of dexamethasone palmitate, possess more potent anti-inflammatory and immunosuppressive properties compared to dexamethasone sodium phosphate. These two formulations have markedly different lipid solubility, resulting in different pharmacokinetic and pharmacodynamic properties. Liposteroid has been used with success in patients with rheumatoid arthritis, macrophage activation syndrome, and idiopathic pulmonary hemosiderosis. In addition, liposteroid has been used in some non-inflammatory diseases. Moreover, we conceive that liposteroid may have a beneficial effect in patients, who are critically ill due to COVID-19, and suffer from the macrophage activation syndrome.

Effect of nonwoven jute agrotextile mulch on soil health and productivity of broccoli (Brassica oleracea L.) in lateritic soil.

A field experiment was conducted in winter season of 2015-2016 in the dry lateritic soil of Eastern India to study the effect of different thicknesses of nonwoven jute agrotextile mulches (NJATM) along with other mulches on soil health, growth and productivity of broccoli (Brassica oleracea L.). The experiment was conducted in randomized block design with six treatments viz., T1 (control, i.e. no mulching), T2 (300 gsm NJATM), T3 (350 gsm NJATM), T4 (400 gsm NJATM), T5 (rice straw) and T6 (black polythene mulch), each of which was replicated four times. The highest average curd weight (355.25 g) and yield (8.53 t ha-1) of broccoli were recorded in T3 treatment. The lowest density of broad leaved weed, sedges and grasses were recorded in T6 treatment which was statistically at par with T4. All the treatments composing of NJATM increased the population of all the soil microbes except bacteria in the root rhizosphere of broccoli from their initial population. On average, the highest population of fungi (54.0 × 103 cfu per g) and actinomycetes (134.75 × 103 cfu per g) was recorded with T3 and T4 treatments respectively in the post-harvest soil. The soil moisture was conserved in all treatments compared to control showing highest moisture content in T4 treatment. Organic carbon and available N, P and K contents of soil were increased in all mulch treated plots compared to control, and their initial value and their highest value were recorded in T3. The NJATM of 350 gsm thickness was very effective compared to other mulches in increasing the growth and productivity of broccoli by suppressing weeds, increasing moisture, microbial population and nutrient content of the lateritic soil.