Insulin Requirements During Severe COVID-19 Were Relatively Low in Japanese Patients With Type 2 Diabetes: Two Case Reports.

The global coronavirus disease 2019 (COVID-19) pandemic has caused myriad adverse effects on the pathology of other diseases. Numerous studies on COVID-19 have reported that, in patients with type 2 diabetes mellitus (T2DM) who have contracted severe COVID-19, glucose metabolism is exacerbated by multiple factors, such as severe inflammation, beta-cell dysfunction caused by the SARS-CoV-2 infection itself, corticosteroid therapy, vasopressor administration, and enteral or parenteral nutrition. Very high doses of insulin are often required in the acute phase of such patients; however, the factors that affect insulin requirements and to what extent remain unclear. A 50-year-old Japanese woman and a 67-year-old Japanese man, both with T2DM and obesity, were admitted to our hospital with severe COVID-19. Both patients required mechanical ventilation and were treated with dexamethasone and tocilizumab, an interleukin-6 (IL-6) receptor monoclonal antibody. Subcutaneous insulin injections failed to control the patients' hyperglycemia, requiring up to 1.83 and 1.81 units/kg/day of intravenous insulin, respectively. Insulin requirements were rapidly decreased with improvement of the respiratory condition, termination of dexamethasone, and discontinuation of tube feeding. Both patients were discharged with oral antidiabetic agents alone. We experienced two Japanese patients who achieved satisfactory glycemic control with a lower intravenous insulin dose than previous reports. Comparing the clinical factors with the previous literature, ethnic differences in insulin sensitivity and the administration of IL-6 receptor antibodies may have been related to the relatively low insulin requirements.

A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety.

Osimertinib is a standard treatment for patients with EGFR-mutated non-small cell lung carcinoma (NSCLC). We evaluated the relationship between plasma osimertinib concentrations and treatment outcome in patients with NSCLC for this cohort study. The plasma levels of osimertinib and its metabolite AZ5104 were measured a week after the start of treatment (P1). The primary endpoint was to evaluate the correlation between plasma concentration and adverse events (AEs). The correlation with treatment efficacy was one of the secondary endpoints. In patients with CNS metastases, the concentration in the cerebrospinal fluid was also measured. Forty-one patients were enrolled. The frequency of AEs was highest for rash, followed by anorexia and thrombocytopenia. Thirty-eight cases provided measurements for P1. The median plasma concentration of osimertinib was 227 ng/mL, and that of AZ5104 was 16.5 ng/mL. The mean CNS penetration rate of two cases was 3.8%. The P1 in the group with anorexia was significantly higher than that in the group without anorexia (385.0 ng/mL vs. 231.5 ng/mL, p = 0.009). Divided into quartiles by P1 trough level, Q2 + Q3 (164-338 ng/mL) had longer PFS, while Q1 and Q4 had shorter PFS. An appropriate plasma level of osimertinib may avoid some adverse events and induce long PFS. Further large-scale trials are warranted.

Randomized phase II trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-squamous non-small cell lung cancer: NJLCG1001.

BACKGROUND: The optimal regimen for concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC) was not definitive. We conducted randomized phase II study, NJLCG0601, and chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy without severe toxicities. Here, we evaluated between this regimen and pemetrexed plus cisplatin in chemoradiotherapy for stage III non-squamous NSCLC. METHODS: Patients with inoperable stage III non-squamous NSCLC were randomly assigned in a 1:1 ratio to UFT 400 mg/m2 on days 1-14 and 29-42, and cisplatin 80 mg/m2 on days 8 and 36 (UP), or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) underwent from day 1 to a total dose of 66 Gy in 33 fractions. Consolidation chemotherapy after CCRT was prohibited for this study. The primary endpoint was defined as 2-year overall survival (OS). This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000003948). RESULTS: From November 2010 to June 2017, 86 patients were entered from 11 institutions. Median follow-up was 54 months. Of the 85 eligible patients, the 2-year OS rate was 78.6% (95% CI, 62.8-88.3%) in UP and 85.5% (95% CI, 70.5-93.2%) in PP. Median PFS and OS was 12.3 and 64.2 months in UP, 26.2 months and not reached in PP, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP group (14.0% vs. 2.0%). CONCLUSIONS: Both UP and PP with IFRT achieved the expected 2-year OS. PP engendered more favorable OS and PFS compared to UP in terms.

Two cases of pseudo-achalasia with lung cancer: Case report and short literature review.

Pseudo-achalasia with lung cancer is a rare complication. We present 2 cases of pseudo-achalasia with lung cancer and summarize previous reports. The previous reports suggested that lung cancer can be complicated with pseudo-achalasia caused by paraneoplastic neurological syndromes rather than direct invasion of the tumor cells to the lower esophageal sphincter, irrespective of the histology of the lung cancer; this can strongly influence the performance status. Treatment for pseudo-achalasia improves not only the symptoms, but also the performance status. Therefore, pseudo-achalasia should be considered when lung cancer patients present with dysphagia without other known causes.

Two cases of endobronchial aspergilloma complicated with primary and metastatic lung cancer: A case report and literature review.

Endobronchial aspergilloma is a rare and unusual presentation of lung aspergilloma; the natural history for such rare diseases is poorly understood. This report presents two cases of endobronchial aspergilloma complicated by primary and metastatic lung cancer, and summarizes previous reports that suggest that an endobronchial lung cancer lesion may promote the colonialization and growth of Aspergillus species in the bronchus. Therefore, if endobronchial aspergilloma is found, the complication of primary or metastatic endobronchial lung cancer should be carefully considered.

Two cases of acute respiratory distress syndrome with high values of Chlamydophila pneumoniae-specific antibodies.

We herein report two cases of acute respiratory distress syndrome (ARDS) with high values of Chlamydophila pneumoniae-specific antibodies. In the first case (a 65-year-old man), high levels of anti-C. pneumoniae antibodies (IgG and IgA) were detected on admission, and the anti-C. pneumoniae IgA level rose by Day 30. The patient was successfully treated with quinolone and steroids. In the second case (an 85-year-old man), abnormally high levels of anti-C. pneumoniae IgM were detected on admission. The patient did not recover, despite receiving treatment with several antibiotics and anti-inflammatory agents. Neither of the patients displayed other pathogen-specific antigens or antibodies. Chlamydophila pneumonia is usually mild, although it can cause severe interstitial pneumonia and ARDS in reinfected patients and the elderly.

Escherichia coli pneumonia in combination with fungal sinusitis and meningitis in a tsunami survivor after the Great East Japan Earthquake.

Individuals who survive near drowning often suffer from complicated infections, including multi-organ and polymicrobial events. This pattern may be especially pronounced among patients exposed to infectious agents during catastrophic events like that of the Great East Japan Earthquake and the associated tsunami disaster. We report here on a patient who presented with Escherichia coli (E. coli) pneumonia in combination with fungal sinusitis and meningitis. A 73-year-old woman survived the tsunami that engulfed the Sanriku coast. By the time of hospital admission, the patient exhibited high fever, severe cough, and sputum production. Chest X-ray and CT scan showed consolidation in the left upper lobe. Administration of an antibacterial agent improved this pneumonia. However, the patient's consciousness was increasingly impaired. Brain CT showed the low-density lesions and partial high-density spot in the sinus, which suggests the fungal infection. MRI showed the inflammation in the sinus spread into the central nerve system. The examination of the cerebrospinal fluid showed the low glucose level, high mononuclear cell count, and highß-D glucan level, the findings of which supported the diagnosis of fungal meningitis. Although the patient improved temporarily in response to combination treatment with anti-fungal agents, no further improvement was seen. In conclusion, this patient, who suffered from infections of pneumonia, sinusitis, and meningitis, presented a quite rare clinical progress. We propose that fungal infection should be taken into consideration in individuals who suffered near drowning, a profile expected to be frequent among tsunami survivors.

Complicated secondary pneumonia after swine-origin influenza A virus infection in an immunocompetent patient.

The pandemic of the swine-origin influenza A virus (S-OIV) in 2009 demonstrated severe viral pneumonia followed by acute respiratory distress syndrome (ARDS). Although ARDS would be caused by the influenza virus pneumonia itself, it has remained unclear whether other respiratory viral or bacterial infections coexist with S-OIV pneumonia. We report an immunocompetent patient with methicillin-resistant Staphylococcus aureus (MRSA) and Herpes simplex virus (HSV) pneumonia secondary to S-OIV infection. A 57-year-old man previously without major medical illness was admitted to our hospital with severe pneumonia accompanied by ARDS due to S-OIV. In his clinical course, anti-influenza treatment was not effective. Sputum culture revealed the presence of MRSA, and HSV was isolated in broncho-alveoler lavage (BAL) fluid. Administration of an antiviral agent (acyclovir), an antibacterial agent (linezolid), and a corticosteroid (methylprednisolone) successfully improved the pneumonia and ARDS. HSV pneumonia can scarcely be seen in healthy people. However recently it has been recognized as a ventilator-associated pneumonia. Although coexistence of Streptococcus pneumoniae and MRSA was reported in S-OIV pneumonia, secondary viral infection has not been reported. The present report is the first patient with HSV pneumonia secondary to S-OIV infection. We propose that a possibility of hidden HSV pneumonia should be taken into consideration in patients with prolonged severe pneumonia due to influenza infection.

Cladosporium species-related hypersensitivity pneumonitis in household environments.

Home-related chronic hypersensitivity pneumonitis (HP) is sometimes difficult to discriminate because patients do not have an obvious history of antigen exposure. We report two HP cases which developed in an office area and in a home: a 47-year-old woman with acute-onset HP and a 72-year-old woman with chronic HP followed up as idiopathic pulmonary fibrosis following isolation of Cladosporium cladosporioides and Cladosporium herbarum, respectively. Lymphocyte stimulating activity and antibody titer to these fungi were increased in these patients. Since Cladosporium spp. and several other fungi are present ubiquitously in our living environment, it is difficult to eliminate the antigen from the patients' environment to control the disease. Cladosporium spp. can be key antigens in inducing chronic HP in the home environment.