Successful treatment with afatinib following the failure of osimertinib rechallenge with osimertinib-induced interstitial lung disease: A case report.

Herein, we report the case of an 84-year-old woman with epidermal growth factor receptor (EGFR) mutation exon 19 deletion postoperative recurrent lung adenocarcinoma. Osimertinib was administered as a first-line treatment; however, she was urgently admitted to our hospital due to dyspnea on the 46th day. Chest computed tomography revealed bilateral diffuse ground-glass opacities (GGOs) suggestive of grade 3 osimertinib-induced interstitial lung disease (ILD). After discontinuation of osimertinib in combination with short-term corticosteroid therapy, widespread GGOs were promptly resolved. As the disease gradually deteriorated after discontinuation of osimertinib, we administered osimertinib (80 mg every other day) followed by careful observation. However, bilateral GGOs re-appeared on the 15th day, and the diagnosis of osimertinib-induced ILD was established. After the improvement in ILD following corticosteroid therapy, afatinib was administered as salvage therapy, resulting in desirable control of lung cancer without any relapse of ILD. Our results indicate that afatinib would be a promising alternative treatment option even in patients who develop osimertinib-induced ILD and experience failure of osimertinib rechallenge.

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019.

BACKGROUND: The serum Krebs von den Lungen-6 (KL-6) level is a predictive factor for acute respiratory distress syndrome (ARDS). The development of ARDS has been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to determine whether serum KL-6 levels are associated with mortality and severity in patients with COVID-19. METHODS: Among 361 Japanese patients with COVID-19 who were hospitalized at Kanagawa Cardiovascular and Respiratory Center between February 2020 and December 2020, 356 patients with data on serum KL-6 levels were enrolled and their medical records were retrospectively analyzed. RESULTS: A negative correlation was observed between KL-6 levels and the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen on admission. The KL-6 levels on admission and the maximal KL-6 levels were higher in patients with severe disease (n = 60) than in those with nonsevere disease (n = 296). Furthermore, the maximal KL-6 levels were higher in nonsurvivors (n = 6) than in survivors (n = 350). In nonsurvivors, the KL-6 levels increased as the disease progressed. The optimal cutoff value of the maximal KL-6 level for discriminating between survivors and nonsurvivors was 684 U/mL, with a sensitivity of 83.3%, a specificity of 90.5%, and an area under the curve of 0.89. CONCLUSIONS: The serum KL-6 level was associated with disease severity. Patients with KL-6 levels ≥684 U/mL had a significantly poorer outcome than those with KL-6 levels <684 U/mL.

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria.

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.

Clinical characteristics of Japanese patients with moderate to severe COVID-19.

INTRODUCTION: Although several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient's characteristics whose disease progressed to severe status. METHODS: The medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1-4 L/min), and severe diseases (oxygen needs of 5 L/min or more). RESULTS: The median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL. CONCLUSIONS: Age and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.

COVID-19 Pneumonia Resembling an Acute Exacerbation of Interstitial Pneumonia.

An 84-year-old man was admitted with hypoxemia and ground-glass opacities with traction bronchiectasis in both lungs and mild fibrosis on computed tomography. We first suspected that he had acute exacerbation of interstitial pneumonia and initiated methylprednisolone pulse therapy. On day 4, he was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia. Although the ground-glass opacities were improved with corticosteroid treatment alone, the hypoxemia persisted, and the plasma D-dimer level increased. Anticoagulant therapy was initiated, and the hypoxemia was improved. COVID-19 pneumonia may result in radiological findings similar to those of acute exacerbation of interstitial pneumonia, and corticosteroids and anticoagulant therapy may lead to favorable outcomes.

Pneumothorax in a COVID-19 Pneumonia Patient without Underlying Risk Factors.

Coronavirus disease 2019 (COVID-19) has been recognized as a worldwide pandemic. However, the clinical course of COVID-19 remains poorly characterized. Although some cases of pneumothorax have been reported, they all had pulmonary complications or were managed with mechanical ventilation. We herein report a case of pneumothorax that developed even though the patient had no pulmonary underlying diseases and had never been managed with mechanical ventilation. In the present case, a lung bulla was found on chest computed tomography during treatment for COVID-19. We concluded that COVID-19 affected the formation of the lung bulla and induced the complication of pneumothorax.

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases.

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.

Species identification, antifungal susceptibility, and clinical feature association of Aspergillus section Nigri isolates from the lower respiratory tract.

Species of Aspergillus section Nigri are generally identified by molecular genetics approaches, whereas in clinical practice, they are classified as A. niger by their morphological characteristics. This study aimed to investigate whether the species of Aspergillus section Nigri isolated from the respiratory tract vary depending on clinical diagnosis. Forty-four Aspergillus section Nigri isolates isolated from the lower respiratory tracts of 43 patients were collected from February 2012 to January 2017 at the National Hospital Organization (NHO) Tokyo National Hospital. Species identification was carried out based on ß-tubulin gene analysis. Drug susceptibility tests were performed according to the Clinical and Laboratory Standards Institute (CLSI) M38 3rd edition, and the clinical characteristics were retrospectively reviewed. A. welwitschiae was isolated most frequently, followed by A. tubingensis. More than half of the A. tubingensis isolates exhibited low susceptibility to azoles in contrast to only one A. welwitschiae isolate. Approximately three quarters of the patients from whom A. welwitschiae was isolated were diagnosed with colonization, whereas more than half the patients from whom A. tubingensis was isolated were diagnosed with chronic pulmonary aspergillosis (CPA). More attention needs to be given to the drug choice for patients with CPA with Aspergillus section Nigri infection because A. tubingensis, which was found to be frequently azole-resistant, was the most prevalent in these patients.

Ten Cases of Intestinal Tuberculosis Which Were Initially Misdiagnosed as Inflammatory Bowel Disease.

Objective Intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) frequently present with similar clinical, endoscopic and pathological features, therefore it is difficult to differentiate between them. The aim of this study was to elucidate the diagnostic delay and prognosis of ITB cases, initially misdiagnosed as IBD. Methods ITB cases were selected from the hospitalized patient list between April 2004 and March 2017 in a tuberculosis center in Japan. We retrospectively evaluated the initial diagnosis, clinical characteristics, endoscopic and pathological findings, bacterial examinations, treatment and prognosis. Results Among 66 ITB patients, ten patients were initially misdiagnosed as IBD. Seven patients were male and the median age was 60.5 years (23-74 years). After the diagnosis of IBD, all the patients were treated with mesalazine, in addition to corticosteroids in two patients and sequential azathioprine and infliximab in one. The median duration of diagnostic delay was 5.5 months (range 0.5-17 months). Eight patients had active pulmonary tuberculosis at the diagnosis of ITB. Acid-fast bacilli were confirmed in four of seven patients by reevaluation of the pathological specimens at the IBD diagnosis. Two patients needed intestinal resection and one with erroneous corticosteroid use for IBD died due to respiratory failure in spite of receiving appropriate treatment for tuberculosis. Conclusion ITB patients were frequently misdiagnosed and treated as IBD, thus resulting in a poor clinical outcome even after finally making a correct diagnosis and administering appropriate treatment. On diagnosis of IBD and/or treatment failure, chest radiograph and acid-fast bacilli of the pathological specimens should be carefully evaluated in order to rule out tuberculosis.

The Sequential Ultrasonographic, Electrophysiological and MRI Findings in a Patient with the Pharyngeal-cervical-brachial Variant of Guillain-Barré Syndrome from the Acute Phase to the Chronic Phase.

Acute progressive weakness in bulbar, neck and limbs is included in several differential diagnoses, including the pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome (GBS). Patients with the PCB variant of GBS are reported to have localized diagnostic cervical spinal nerve abnormalities that can be examined by nerve ultrasonography (NUS) and magnetic resonance neurography (MRN). We herein report the case of a 77-year-old man with the PCB variant of GBS. Although the nerve conduction study (NCS) findings were indirect indicators for an early diagnosis, the combination of NCS and NUS was a useful complementary measure that facilitated an early diagnosis. MRN did not show any apparent diagnostic abnormalities. After early treatment, the patient was discharged and returned home.