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Background/Aims: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory syndrome. The mechanisms underlying the different degrees of pneumonia severity in patients with COVID-19 remain elusive. This study provides evidence that COVID-19 is associated with eosinophil-mediated inflammation.Methods: We performed a retrospective case series of three patients with laboratory and radiologically confirmed COVID-19 pneumonia admitted to Chosun University Hospital. Demographic and clinical data on inflammatory cell lung infiltration and cytokine levels in patients with COVID-19 were collected.Results: Cytological analysis of sputum, tracheal aspirates, and bronchoalveolar lavage fluid (BALF) samples from all three patients revealed massive infiltration of polymorphonuclear cells (PMNs), such as eosinophils and neutrophils. All sputum and BALF specimens contained high levels of eosinophil cationic proteins. The infiltration of PMNs into the lungs, together with elevated levels of natural killer T (NKT) cells in BALF and peripheral blood samples from patients with severe pneumonia in the acute phase was confirmed by flow cytometry.Conclusions: These results suggest that the lungs of COVID-19 patients can exhibit eosinophil-mediated inflammation, together with an elevated NKT cell response, which is associated with COVID-19 pneumonia.

BACKGROUND The roots of Achyranthes japonica Nakai (AJN), called “Useul-puli,” has been traditionally used to control pain and improve dysfunction in osteoarthritis patients in South Korea. CASE SUMMARY We described 3 patients diagnosed with herbal medicine induced interstitial lung disease after consuming boiled the roots of AJN. They were referred to our hospital because of the modified Medical Research Council grade 4 dyspnea. Chest computed tomography showed bilateral ground-glass opacities with patchy consolidation. After treatment with systemic glucocorticoid therapy and discontinuation of the roots of AJN, their symptoms improved, and almost all ground-glass opacities and patchy consolidations on chest radiography and chest computed tomography resolved. CONCLUSION We present three cases of interstitial lung disease induced by the roots of AJN.

Background/Aims: Secondary infection with influenza virus occurs in critically ill patients and is associated with substantial morbidity and mortality; however, there is limited information about it in patients with severe coronavirus disease 2019 (COVID-19). Thus, we investigated the clinical outcomes of and risk factors for secondary infections in patients with severe COVID-19.Methods: This study included patients with severe COVID-19 who were admitted to seven hospitals in South Korea between February 2020 to February 2021. Multivariate logistic regression analyses were performed to assess factors associated with the risk of secondary infections.Results: Of the 348 included patients, 104 (29.9%) had at least one infection. There was no statistically significant difference in the 28-day mortality (17.3% vs. 12.3%, p = 0.214), but in-hospital mortality was higher (29.8% vs. 15.2%, p = 0.002) in the infected group than in the non-infected group. The risk factors for secondary infection were a high frailty scale (odds ratio [OR], 1.314; 95% confidence interval [CI], 1.123 to 1.538; p = 0.001), steroid use (OR, 3.110; 95% CI, 1.164 to 8.309; p = 0.024), and the application of mechanical ventilation (OR, 4.653; 95% CI, 2.533 to 8.547; p < 0.001).Conclusions: In-hospital mortality was more than doubled in patients with severe COVID-19 and secondary infections. A high frailty scale, the use of steroids and application of mechanical ventilation were risk factors for secondary infection.

BACKGROUND: Pembrolizumab is a highly selective IgG4 kappa isotype monoclonal antibody against the programmed cell death-1 (PD-1) molecule. In the treatment of non-small cell lung cancer (NSCLC), pembrolizumab has demonstrated significant efficacy, significant survival outcomes, long-lasting responses, and a good safety profile compared with cytotoxic chemotherapy. CASE SUMMARY: A 79-year-old Korean male presented with a left side palpable neck mass. An ultrasound-guided core-needle biopsy of the largest neck mass was performed, and squamous cell carcinoma was confirmed based on the histological and immunohistochemical findings. He was diagnosed with squamous cell carcinoma of the lung with multiple lymph nodes and rib metastases (T1N3M1b, Stage IVA) using enhanced chest computed tomography and (18)F-fluorodeoxyglucose positron emission/computed tomography. After 4 cycles of gemcitabine and carboplatin, we clinically judged the disease as progressive. Owing to the high PD-1 expression demonstrated by the patient, pembrolizumab was initiated (200 mg every 3 wk). After 3 cycles of pembrolizumab, a complete response was achieved. At the 4(th) cycle of pembrolizumab, the white blood cell count was markedly elevated. Peripheral blood smear analysis and bone marrow biopsy were performed. The patient was diagnosed with acute myelomonocytic leukemia. CONCLUSION: We present the first report of acute myelomonocytic leukemia during pembrolizumab treatment in an NSCLC patient; the mechanism remains unknown.

BACKGROUND: The impact of mechanical ventilation parameters and management on outcomes of patients with coronavirus disease 2019 (COVID-19) ARDS is unclear. METHODS: This multi-center observational study enrolled consecutive mechanically ventilated patients with COVID-19 ARDS admitted to one of 7 Korean ICUs between February 1, 2020–February 28, 2021. Patients who were age < 17 y or had missing ventilation parameters for the first 4 d of mechanical ventilation were excluded. Multivariate logistic regression was used to identify which strategies or ventilation parameters that were independently associated with ICU mortality. RESULTS: Overall, 129 subjects (males, 60%) with a median (interquartile range) age of 69 (62–78) y were included. Neuromuscular blocker (NMB) use and prone positioning were applied to 76% and 16% of subjects, respectively. The ICU mortality rate was 37%. In the multivariate analysis, higher dynamic driving pressure (ΔP) values during the first 4 d of mechanical ventilation were associated with increased mortality (adjusted odds ratio 1.16 [95% CI 1.00–1.33], P = .046). NMB use was associated with decreased mortality (adjusted odds ratio 0.27 [95% CI 0.09–0.81], P = .02). The median tidal volume values during the first 4 d of mechanical ventilation and the ICU mortality rate were significantly lower in the NMB group than in the no NMB group. However, subjects who received NMB for ≥ 6 d (vs < 6 d) had higher ICU mortality rate. CONCLUSIONS: In subjects with COVID-19 ARDS receiving mechanical ventilation, ΔP during the first 4 d of mechanical ventilation was independently associated with mortality. The short-term use of NMB facilitated lung-protective ventilation and was independently associated with decreased mortality.

Old age is associated with disease severity and poor prognosis among coronavirus disease 2019 (COVID-19) cases; however, characteristics of elderly patients with severe COVID-19 are limited. We aimed to assess the clinical characteristics and outcomes of patients hospitalized with severe COVID-19 at tertiary care centers in South Korea. This retrospective multicenter study included patients with severe COVID-19 who were admitted at seven hospitals in South Korea from 2 February 2020 to 28 February 2021. The Cox regression analyses were performed to assess factors associated with the in-hospital mortality. Of 488 patients with severe COVID-19, 318 (65.2%) were elderly (≥65 years). The older patient group had more underlying diseases and a higher severity score than the younger patient group. The older patient group had a higher in-hospital mortality rate than the younger patient group (25.5% versus 4.7%, p-value < 0.001). The in-hospital mortality risk factors among patients with severe COVID-19 included age, acute physiology and chronic health evaluation II score, presence of diabetes and chronic obstructive lung disease, high white blood cell count, low neutrophil-lymphocyte ratio and platelet count, do-not-resuscitate order, and treatment with invasive mechanical ventilation. In addition to old age, disease severity and examination results must be considered in treatment decision-making.

Background The ratio of oxygen saturation (ROX) index, defined as the ratio of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate, can help identify patients with hypoxemic respiratory failure at high risk for intubation following high-flow nasal cannula (HFNC) initiation; however, whether it is effective for predicting intubation in coronavirus disease 2019 (COVID-19) patients receiving HFNC remains unknown. Moreover, the SpO2/FiO2 ratio has been assessed as a prognostic marker for acute hypoxemic respiratory failure. This study aimed to determine the utility of the ROX index and the SpO2/FiO2 ratio as predictors of failure in COVID-19 patients who received HFNC. Methods This multicenter study was conducted in seven university-affiliated hospitals in Korea. Data of consecutive hospitalized patients diagnosed with COVID-19 between February 10, 2020 and February 28, 2021 were retrospectively reviewed. We calculated the ROX index and the SpO2/FiO2 ratio at 1 h, 4 h, and 12 h after HFNC initiation. The primary outcome was HFNC failure defined as the need for subsequent intubation despite HFNC application. The receiver operating characteristic curve analysis was used to evaluate discrimination of prediction models for HFNC failure. Results Of 1,565 hospitalized COVID-19 patients, 133 who received HFNC were analyzed. Among them, 63 patients (47.4%) were successfully weaned from HFNC, and 70 (52.6%) were intubated. Among patients with HFNC failure, 32 (45.7%) died. The SpO2/FiO2 ratio at 1 h after HFNC initiation was an important predictor of HFNC failure (AUC 0.762 [0.679–0.846]). The AUCs of SpO2/FiO2 ratio at 4 h and ROX indices at 1 h and 4 h were 0.733 (0.640–0.826), 0.697 (0.597–0.798), and 0.682 (0.583–0.781), respectively. Multivariable analysis showed that the patients aged ≥70 years are 3.4 times more likely to experience HFNC failure than those aged p = 0.009). The SpO2/FiO2 ratio (HR 0.983 [0.972–0.994], p = 0.003) at 1 h was significantly associated with HFNC failure. Conclusions The SpO2/FiO2 ratio following HFNC initiation was an acceptable predictor of HFNC failure. The SpO2/FiO2 ratio may be a good prognostic marker for predicting intubation in COVID-9 patients receiving HFNC.

The aim of this study was to determine whether the late failure of high-flow nasal cannula (HFNC) is associated with mortality in patients with coronavirus disease 2019 (COVID-19). This multicenter study included seven university-affiliated hospitals in the Republic of Korea. We collected the data of patients hospitalized with COVID-19 between 10 February 2020 and 28 February 2021. Failure of HFNC was defined as the need for mechanical ventilation despite HFNC application. According to the time of intubation, HFNC failure was divided into early failure (within 48 h) and late failure (after 48 h). During the study period, 157 patients received HFNC and 133 were eligible. Among them, 70 received mechanical ventilation. The median time from HFNC initiation to intubation of the early failure group was 4.1 h (interquartile range [IQR]: 1.1–13.5 h), and that of the late failure group was 70.9 h (IQR: 54.4–145.4 h). Although the ratio of pulse oximetry/fraction of inspired oxygen (ROX index) within 24 h of HFNC initiation tended to be lower in the early failure group than in the late failure group, the ROX index before two hours of intubation was significantly lower in the late failure group (odds ratio [OR], 5.74 [IQR: 4.58–6.98] vs. 4.80 [IQR: 3.67–5.97], p = 0.040). The late failure of HFNC may be associated with high mortality in COVID-19 patients with acute respiratory failure.

BACKGROUND Bronchobiliary fistula (BBF) is a rare disease characterized by an abnormal connection between the biliary system and bronchi. Traditional causes of BBF include trauma and infections, and more recent causes include malignancies and certain cancer treatments. Ramucirumab is an antivascular endothelial growth factor receptor 2 monoclonal antibody, currently used as a second-line treatment for gastric cancer. CASE SUMMARY A 43-year-old man visited our hospital with the complaint of jaundice. He was diagnosed with inoperable advanced gastric cancer owing to invasion of the hepatic hilum by the tumor. After percutaneous transhepatic biliary drainage (PTBD) and stent placement, capecitabine and oxaliplatin were administered as first-line palliative chemotherapy. The tumor progressed, and paclitaxel and ramucirumab were administered as second-line chemotherapy. However, on the first day of the second cycle, the patient suddenly developed dyspnea and pneumonia. BBF was diagnosed on the basis of the presence of bilious sputum and the results of computed tomography, and PTBD was repeated. CONCLUSION This is the first report of BBF after administration of the new antiangiogenic agent ramucirumab.

Patient: Male, 51 Final Diagnosis: Spontaneous tumor lysis syndrome • idiopathic primary myelofibrosis Symptoms: Abdominal pain • general weakness Medication: — Clinical Procedure: Continuous renal replacement therapy • bone marrow biopsy Specialty: Hematology Objective: Rare disease Background: Tumor lysis syndrome (TLS) is an oncologic emergency resulting from the massive destruction of tumor cells after cytotoxic chemotherapy for chemosensitive malignancies with a high tumor burden. Its clinical manifestations include severe electrolyte disturbances, metabolic acidosis, acute renal failure secondary to urate deposition in the kidney, heart, and skeletal muscle, and nervous system dysfunction. We report an extremely rare case of spontaneous TLS (STLS) in idiopathic primary myelofibrosis (PMF). Case Report: A 51-year-old Korean man was admitted to our hospital with general weakness and left-side abdominal pain. The patient was diagnosed with acute urate nephropathy with hyperphosphatemia, hyperkalemia, hypocalcemia, and metabolic acidosis. Splenomegaly was accompanied by leukocytosis and a peripheral blood smear revealed immature granulocytes without blast cells. Bone marrow biopsy showed PMF. Initially, we presumed it was a spontaneous tumor lysis syndrome of PMF. We immediately performed emergency hemodialysis. We concluded that the patient, who had chronic hyperuricemia due to undiagnosed PMF, was recently admitted to the emergency room with STLS due to overwork and dehydration. Conclusions: We present an extremely rare case of STLS in idiopathic PMF. The mechanism of chronic hyperuricemia in our case might be rapid cell turnover due to ineffective erythropoiesis of PMF.

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation is associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of FcγR signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients., Graphical Abstract, Kim et al. find that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. Increased Th2-biased immune responses, accompanying overt complement activation, are seen in the critical group. These findings suggest that enhanced eosinophil-mediated inflammation and dysregulated humoral responses might be drivers of severe COVID-19.

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we conducted kinetic profiling of respiratory leukocytes and associated inflammatory mediators to show that severe COVID-19 is associated with delayed but enhanced eosinophilic inflammation when compared to mild cases. In addition, we confirmed increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the severe group. Moreover, enhanced antibody responses and complement activation was associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from a fatal case, as well as by enhanced hallmark gene set signatures of FcgR signaling and complement activation in myeloid cells of respiratory specimens from severe COVID-19 patients. We also observed expression of viral antigen in lung epithelial and endothelial cells without producing viruses during late stage of COVID-19, indicating abortive viral infection which may further fuel antibody responses and aggravate immune-complex-mediated inflammation. These results suggest that SARS-CoV-2 infection may drive scripted specific innate immune responses, including eosinophilic inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of severe pneumonia in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)1 and often results in fatal pneumonia.2,3 Despite the worldwide effect of the COVID-19 pandemic, the underlying mechanisms of the fatal viral pneumonia remain elusive. Here, we investigated respiratory specimens, including broncholoalveolar lavage fluids (BALFs) and bloods collected from three confirmed cases of COVID-19 patients with varying degrees of disease severity. Surprisingly, over 35% of cells from BALFs obtained from two pneumonic patients was comprised of eosinophils, while 20% was comprised of lymphocytes. Cytological analysis of sputa and tracheal aspirates from all three patients also revealed that more than 90% of total cells were eosinophils. Infiltration of CD16+/CD24+ polymorphonuclear cells into lungs, together with elevated NKT cells in BALFs and peripheral blood samples, in patients with severe pneumonia was confirmed by flow cytometry. Moreover, rapid and profound IgE responses against the N protein of SARS-CoV-2 was only detected in plasma from a patient suffering from more severe and prolonged pneumonia. A significant reduction in oxygen demand with improved chest imaging was observed in two severe COVID-19 patients after treatment with a steroid, methylprednisolone. The present study provides evidence that acute eosinophilic pneumonia4 is associated with COVID-19.

A culture of the Leptospira species and the microscopic agglutination test (MAT) are considered as the reference standard for the diagnosis of leptospirosis, but both tests are imperfect for early diagnosis. We describe 4 patients diagnosed with leptospirosis using nested polymerase chain reaction (N-PCR) that targeted the 16S rRNA gene and the passive hemagglutination assay (PHA). In our 4 cases, Leptospira DNA in the urine, plasma, or cerebrospinal fluid (CSF), was detected by N-PCR in the early phase of leptospirosis, except in the sample from the buffy coat. Especially, case 3 showed that N-PCR with the urine and CSF was positive 8 days after symptom onset, but not for the plasma or buffy coat. We report 4 cases of leptospirosis that were diagnosed by N-PCR that targeted the 16S rRNA gene with urine, plasma, or CSF, but not the buffy coat. Three were cured by doxycycline but the case 4 was fatal. Detection of Leptospira DNA by PCR from the urine and CSF, in addition to plasma, may be helpful to confirm the diagnosis., Graphical Abstract

Background Inflammatory myofibroblastic tumor is a rare benign neoplasm that frequently involves the lung and abdominopelvic region, and is found mainly in children and young adults. Inflammatory myofibroblastic tumor tends to be locally invasive or recurrent, and rarely metastasizes. Case presentation A 76-year-old Korean man presented with a history of upper back pain for 2 months and motor weakness in both lower extremities for 2 days. Contrast-enhanced computed tomography of his chest and abdomen showed a large heterogeneous pleural mass involving the right fifth rib and vertebral body and a mass infiltrating the right renal hilum. Computed tomography-guided percutaneous needle biopsy of the pleural mass was performed. The histological findings on hematoxylin and eosin staining showed proliferation of spindle cells with infiltration of lymphocytes and plasma cells. Immunohistochemistry showed neoplastic cells positive for CD68, focally positive for smooth muscle actin, and negative for cytokeratin and desmin. Inflammatory myofibroblastic tumor was diagnosed based on the histological examination. Treatment with glucocorticoids (methylprednisolone 1 mg/kg) and radiotherapy (5 days/week for 3 weeks at 3 Gy/fraction, 45 Gy/15 days) was started. After 1 month, chest computed tomography showed a reduction in the size of the pleural mass, and abdominopelvic computed tomography showed decreased infiltration around the right renal pelvis. Conclusions Inflammatory myofibroblastic tumor is a rare neoplasm of intermediate malignant potential due to a tendency for local recurrence and it rarely develops distant metastases. Complete surgical resection is the primary treatment. However, unresectable and metastatic inflammatory myofibroblastic tumor can be treated with systemic therapy, including glucocorticoids, radiotherapy, and/or chemotherapy.

Bronchial carcinoid tumor accounts for less than 5% of all primary lung tumors in adults. Although surgical resection is the treatment of choice, here we report a case of bronchial carcinoid tumor treated with flexible bronchoscopic resection. A 19-year-old-man presented with a history of wheezing with dyspnea for six months. A simple chest x-ray showed no abnormal findings, but a pulmonary function test showed a moderate obstructive lung disease pattern without a bronchodilator response. A computed tomogram of the thorax revealed an enhanced 15×12 mm nodule in the left main bronchus. Bronchoscopic examination showed a polypoid mass with a stalk in the left main bronchus, which almost completely occluded the left main bronchus. Histopathology of the resected specimen revealed a bronchial carcinoid tumor. We treated the carcinoid tumor with a flexible bronchoscopic resection. During the follow up period of 6 months, the previous tumor didn't relapse. Initial bronchoscopic resection should be considered when bronchial carcinoid tumor can be approached by bronchoscopy.

Cytomegalovirus (CMV) infection is associated with an exacerbations of systemic lupus erythematosus (SLE), but the role of CMV in disease pathogenesis remains unclear. CMV infection is often severe and difficult to diagnose in patients with SLE. Only a few cases of opportunistic CMV interstitial pneumonitis infection occurring in patients with SLE after intensive immunosuppressive therapy have been described. We report a case of CMV infection presenting with massive pericarditis and aggravating lupus nephritis