CRISPR-Cas9-mediated gene therapy in lung cancer

As the largest cause of cancer-related deaths worldwide, pulmonary cancer is the most common form of the disease. Several genetic, epigenetic, and environmental factors come into play during the multi-step mechanism of tumorigenesis. The heterogeneity that makes discovering successful therapeutics for pulmonary cancer problematic is significantly influenced by the epigenetic landscape, including DNA methylation, chromatin architecture, histone modifications, and noncoding RNA control. Clinical activity of epigenetic-targeted medicines has been reported in hematological tumors, and these compounds may also have therapeutic effects in solid tumors. Over the course of the past few years, some researchers have successfully modified the expression of genes in cells using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) technique. The utilization of this technology allows for the induction of site-specific mutagenesis, epigenetic alterations, and the regulation of gene expression. This study will present an overview of the primary epigenetic alterations seen in pulmonary cancer, as well as a summary of therapeutic implications for targeting epigenetics in the management of pulmonary cancer, with a particular emphasis on the technique known as CRISPR/Cas9 (AU)

Coincidence of Candida Endophthalmitis, and Aspergillus and Pneumocystis jirovecii Pneumonia in a COVID-19 Patient: Case Report.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with immune system dysfunction and makes patients vulnerable to opportunistic infections. This report presents a patient with a history of COVID-19, suffering from opportunistic infections. CASE DESCRIPTION: We reported a 64-year-old man complaining of progressive visual loss in his left eye, who had previously been hospitalized for three weeks due to COVID-19. In the ophthalmologic assessment, large foci of dense subretinal and intraretinal infiltrations involving the macula were observed (compatible with endogenous fungal endophthalmitis). Real-time PCR result of intraocular fluid was positive for Candida spp. During subsequent hospitalization, the patient also suffered from fever and productive coughs (manifestations of pneumonia caused by Aspergillus fumigatus and Pneumocystis jirovecii). In response to antibiotic therapy, the fever and coughs subsided, and the ocular examination revealed a dramatic decrease in the size of retinal infiltrations. CONCLUSIONS: In patients with severe COVID-19, long-term ICU admission and immunosuppressive drugs lead to immune system dysfunction and make the patient more susceptible to opportunistic infections. Consequently, fungal pathogens such as Aspergillus, Pneumocystis jirovecii, and Candida spp. may cause infection in different body organs. Thus, clinicians should be alert and have clinical suspicion to diagnose accurately and manage patients accordingly.

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial.

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508).

Immunogenic cell death (ICD)-inducers in non-small-cell lung carcinoma (NSCLC): current knowledge and future perspective

The prevalence of non-small-cell lung cancer (NSCLC) is rising every year all around the world. The interaction between cancer cells and the tumor microenvironment (TME) is a crucial factor in determining the development of human neoplasms. Organellar and cellular stress are induced during immunogenic cell death (ICD), a particularly functional response pattern. ICD is a separate but poorly characterized entity caused by various cancer treatments. The induction of ICD has the potential to change TME and the recruitment of tumor-infiltrating lymphocytes (TILs), and the coupling of ICD-inducers and other therapeutic approaches can have a synergistic role in boosting anticancer impacts. The purpose of this study is to review the studies in the field of NSCLC using ICD-inducers as a treatment strategy or as a combination therapy. This review provide for researches a better view of what has been done so far and the challenges they face in the future (AU)

CRISPR-Cas9-mediated gene therapy in lung cancer.

As the largest cause of cancer-related deaths worldwide, pulmonary cancer is the most common form of the disease. Several genetic, epigenetic, and environmental factors come into play during the multi-step mechanism of tumorigenesis. The heterogeneity that makes discovering successful therapeutics for pulmonary cancer problematic is significantly influenced by the epigenetic landscape, including DNA methylation, chromatin architecture, histone modifications, and noncoding RNA control. Clinical activity of epigenetic-targeted medicines has been reported in hematological tumors, and these compounds may also have therapeutic effects in solid tumors. Over the course of the past few years, some researchers have successfully modified the expression of genes in cells using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) technique. The utilization of this technology allows for the induction of site-specific mutagenesis, epigenetic alterations, and the regulation of gene expression. This study will present an overview of the primary epigenetic alterations seen in pulmonary cancer, as well as a summary of therapeutic implications for targeting epigenetics in the management of pulmonary cancer, with a particular emphasis on the technique known as CRISPR/Cas9.

Immunogenic cell death (ICD)-inducers in non-small-cell lung carcinoma (NSCLC): current knowledge and future perspective.

The prevalence of non-small-cell lung cancer (NSCLC) is rising every year all around the world. The interaction between cancer cells and the tumor microenvironment (TME) is a crucial factor in determining the development of human neoplasms. Organellar and cellular stress are induced during immunogenic cell death (ICD), a particularly functional response pattern. ICD is a separate but poorly characterized entity caused by various cancer treatments. The induction of ICD has the potential to change TME and the recruitment of tumor-infiltrating lymphocytes (TILs), and the coupling of ICD-inducers and other therapeutic approaches can have a synergistic role in boosting anticancer impacts. The purpose of this study is to review the studies in the field of NSCLC using ICD-inducers as a treatment strategy or as a combination therapy. This review provide for researches a better view of what has been done so far and the challenges they face in the future.

Case Report: Pneumonia in a Patient With Combined Variable Immunodeficiency: COVID-19 or Pneumocystis Pneumonia?

Combined variable immunodeficiency (CVID) is a primary immunodeficiency, characterized by impairment in immune system function. These patients are susceptible to opportunistic infections, which may mimic COVID-19 manifestations. Also, misdiagnosis or delayed diagnosis of opportunistic infections can lead to perilous consequences. We report a 28-year-old woman with a history of combined variable immunodeficiency disorder (CVID) and ulcerative colitis (UC) complained of fever, cough, and dyspnea. According to the clinical and radiological manifestations and the COVID-19 epidemic, she was admitted with a primary diagnosis of COVID-19 pneumonia. After a week, the patient did not respond to treatment, so she underwent bronchoscopy. Using polymerase chain reaction (PCR) methodology, we detected DNA of Pneumocystis jirovecii, the causative agent of a life-threatening pneumonia (PCP), in respiratory specimens. The patient was hypersensitive to common PCP treatments, so she was treated with high-dose clindamycin. However, the patient's clinical condition aggravated. Besides, we found evidence of pneumothorax, pneumomediastinum, and pneumopericardium in chest CT scan. We inserted a catheter for the patient to evacuate the air inside the mediastinum. Also, we added caspofungin to the treatment. The patient eventually recovered and was discharged from the hospital about a week later. Thus, during the COVID-19 epidemic, in febrile patients with respiratory symptoms, physicians should not think only of COVID-19. They must consider opportunistic infections such as PCP, especially in immunocompromised patients.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Adding Colchicine to the Antiretroviral Medication - Lopinavir/Ritonavir (Kaletra) in Hospitalized Patients with Non-Severe Covid-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomized Controlled Trial.

OBJECTIVES: Colchicine is a well-known drug, which has been used for years to treat a wide range of rheumatic and inflammatory disorders. It helps break the cycle of inflammation through diverse mechanisms including reducing Intereukin-6, Interleukin-8, Tumour Necrosis Factor-alpha besides controlling oxidative stress pathways which all are important and pathologic components in the clinical course and outcome of patients infected with COVID-19. This study aims to assess the anti-inflammatory effects of colchicine in non-severe hospitalized COVID-19 patients. TRIAL DESIGN: Prospective, randomized (1:1 ratio), double blind study with parallel group design. PARTICIPANTS: Hospitalized patients with positive nasopharyngeal swab for COVID-19 infection (RT -PCR) and lung Computed tomography scan involvement compatible with COVID-19 pneumonia. The patients are not severely hypoxic, do not need intubation or invasive oxygenation. EXCLUSION CRITERIA: known hypersensitivity to colchicine; known hepatic failure; estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2 (by the CKD-EPI Creatinine Equation for Glomerular Filtration Rate (GFR) which estimates GFR based on serum creatinine. ; kidney transplant recipients, using Digoxin, QTc >450 msec. Participants will be recruited from inpatients at Labbafinejad Meidcal Center , Tehran, Iran. INTERVENTION AND COMPARATOR: Eligible enrolled patients will be randomized into two groups. Group A will receive the antiretroviral Lopinavir/Ritonavir (Kaletra) while group B will receive Lopinavir/Ritonavir (Kaletra) + Colchicine 1.5 mg loading then 0.5 mg twice daily orally. All patients in both groups will receive the same amounts of essential minerals, vitamins as antioxidants, and antibiotics. Patients of both groups will be treated under optimal treatment based on the CDC and WHO guidelines and national consensus proposed in Iran including the same dosages of Lopinavir/Ritonavir, antibiotics, trace elements and antioxidants while only in group-B patients Colchicine will be added on top of this protocol. MAIN OUTCOMES: Primary: Time for clinical improvement and lung CT score changes 14 days after treatment. Secondary: 14 days after treatment - C-Reactive Protein test x Neutrophil to Lymphocyte Ratio , Interleukin-6, malondialdehyde (MDA) levels reduction - Percentage of patients who require supplemental Oxygen - Mean hospital stay length RANDOMISATION: Patients will be allocated to each group (ratio 1:1) by using an online randomization tool: http://www.graphpad.com/quickcalcs/index.cfm BLINDING (MASKING): This will be a double-blind study in which participants and those assessing the final outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Regarding the pandemic crisis and our center capacity to hospitalize confirmed COVID-19 patients, a total of 80 patients was found to be logical to be randomized into two groups of 40- patients. TRIAL STATUS: Recruitment is ongoing. Recruitment began on 20/03/2020 and the date by which the recruitment is anticipated to be completed is 30/05/2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04360980, registered 24/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Identification of Sonographic Features for Predicting Benign Versus Malignant Mediastinal or Hilar Lymph Nodes Using Endobronchial Ultrasound.

OBJECTIVES: In countries with a high prevalence of tuberculosis, such as Iran, the differentiation of malignant from non-malignant tumors is crucial. We attempted to find a reliable model in determining malignant nodes by investigating the sonographic characteristics of lymph nodes (LNs). METHODS: In this prospective study, the morphologic characteristics of LNs, including size, shape, vascular pattern, echogenicity, margin, coagulation necrosis sign, calcification, and central hilar structure, which had been obtained during endobronchial ultrasound-guided transbronchial needle aspiration, were compared with the final pathology results. RESULTS: We examined 253 LNs from 93 patients. Round shape, non-hilar vascular pattern, heterogeneous echogenicity, hyperechogenicity, distinct margin, and the existence of necrosis signs were significantly higher in malignant nodes. On the other hand, the existence of calcification, as well as the presence of central hilar structure, were highly suggestive of benign nodes (p < 0.050). Multivariate logistic regression revealed that size > 1 cm, heterogeneous echogenicity, hyperechogenicity, the existence of necrosis signs, and the lack of central hilar structure are independent predictive factors for malignancy. The accuracy of each of the aforementioned characteristics are 42.3%, 71.5%, 71.9%, 73.5%, and 65.6%, respectively. Of 74 malignant LNs, 100% had at least one of these independent factors. CONCLUSIONS: The morphological features of LNs based on endobronchial ultrasound-guided transbronchial needle aspiration can play a role in predicting malignancy.

Nephrologist, Pulmonologist Connection: From Bench to Bedside, Mini Review.

Whether working in intensive care unit or not as nephrologists we are all facing complicated cases with different sign and symptoms. Among them is a category of patients presenting with concomitant respiratory and kidney failure called pulmonary renal syndrome, which needs mutual connection between nephrologist and pulmonologist closely for the best decision-making. Although this is not a common entity, still associated with high rate of morbidity and mortality involving diffuse alveolar hemorrhage and glomerulonephritis. Understanding the updates in the field of management would benefit both the patients and caregivers providing clear answers to present obstacles.

Clinical features and short-term outcomes of COVID-19 in Tehran, Iran: An analysis of mortality and hospital stay.

Background The sudden outbreak of the COVID-19 disease originated in Wuhan, China, in December 2019. There have been few reports of the clinical course of the disease, but detailed information on the risk factors for increased hospital stay and mortality is not available. In this study, we aimed to present the details of 53 confirmed COVID-19 cases to share the clinical course and the risk factors for longer hospital stay and death. Methods In this study, we enrolled fifty-three patients with confirmed COVID-19 infection from a referral academic hospital in Tehran, Iran admitted between March and April 2020. Patients' demographics, laboratory tests, treatments, length of hospital stay (LOHS), and final outcome were recorded and analyzed. Results Fifty-three patients were included in this study. The higher LOHS was associated with clinical symptoms, including hemoptysis (IRR= 0.73, P-value= 0.02), diarrhea (IRR= 0.78, P-value= 0.01), headache (IRR= 0.81, P-value= 0.05), and dry cough (IRR= 0.82, P-value= 0.05). Mortality was associated with older age(Odds ratio=1.148, 95%CI=1.032-1.276), lower calcium level (Odds ratio=0.087, 95%CI=0.010-0.788), lower serum albumin (Odds ratio=0.036, 95%CI=0.002-0.655), as well as increased level of neutrophil/lymphocyte ratio (NLR) (Odds ratio=1.468, 95%CI=1.086-1.985), lactate dehydrogenase (LDH) (Odds ratio=1.004, 95%CI=1.000-1.007), and urea (Odds ratio=1.023, 95%CI=1.006-1.039).  Conclusion Our study identified that decreased levels of O2saturation, platelet count, calcium, albumin, and increased NLR, LDH, urea, and old age were correlated with mortality. Also, LOHS was significantly associated with clinical findings, such as hemoptysis and diarrhea.