[Survey of spike-specific immunoglobulin G antibodies at approximately 3 months and 9 months after vaccination against coronavirus disease 2019 (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) in health care workers].

OBJECTIVE: We investigated the antibody titer of spike-specific immunoglobulin G (IgG) antibodies after receiving coronavirus repair uridine ribonucleic acid (RNA) vaccine (BNT162b2, Pfizer) in health care workers. METHODS: At one hospital, health care workers received the vaccination between February and May 2021. A survey using questionnaires and spike-specific IgG antibody tests (Abbott) was conducted in 293 participants who had been vaccinated at least once and consented to this study at the time of medical checkups between April and May 2021. We calculated the antibody titer in each age group and days post-vaccination. We examined whether antibody titers of 4,000 AU/mL or higher (probability of high titer: approximately 95%, Abbott) were associated with adverse reactions after vaccination. In addition (1), the antibody titers at approximately 100 days after the second vaccination in 11 participants were remeasured. Furthermore (2), the antibody titers at approximately 260 days after the second vaccination in 13 participants were remeasured and compared with the initial measurements. RESULTS: Of the participants, 276 were post-2 doses (A), 14 were post-1 dose (B), and 3 discontinued the second vaccination (C) at the time of health checkup. The median antibody titer was 11,045.8 AU/mL (50.7-40,000) in group A, 122.7 AU/mL (2.6-1,127.0) in group B, 27,099.3 AU/mL in one of group C who had recovered from coronavirus disease 2019 (COVID-19), and 574.2 AU/mL (283.3 and 865.1) in the other two of group C. The median antibody titer was the highest in those in their 20s, and there was a significant difference between those under and above 40 years of age. The median titer was the highest in 2 weeks to 1 month after the second vaccination. After the second dose, fatigue (≥ moderate) was associated with antibody titers of 4,000 AU/mL or higher. The antibody titers of 11 and 13 participants at approximately 100 and 260 days after the second vaccination were significantly lower than those at the first measurement, with median values of 2,838.0 AU/mL (832.9-5,698.6) and 512.0 AU/mL (154.0-1,220.0), respectively. CONCLUSIONS: Antibody titers were higher in participants under 40 years of age than those 40 years or older. In addition, the percentage of high antibody titer (≧ 4,000 AU/mL) was higher in those who had severe fatigue after the second vaccination. The peak of antibody titer after the second dose was approximately 1 month, and the titer may decline gradually.

[A Case Strongly Suspected of Being Pulmonary Toxocariasis Showing Multiple Pulmonary Nodules with a Disappearing and Reappearing Halo Sign].

We report herein on a case strongly suspected of being pulmonary toxocariasis. A 22-year-old Indonesian man referred to our hospital presented with abnormal chest shadows upon medical examination. He had no symptoms. He did not have any pets nor did he eat raw beef or chicken. Hematological examination revealed eosinophilia and elevation of IgE. Chest computed tomography revealed 3 pulmonary nodules with the halo sign. We suspected a parasite infection and performed antiparasite antibody testing. Ascaris suum was slightly positive on the screening test. As specific antibody against the larval excretory-secretory products of Toxocara canis, measured at the National Institute of Infectious Diseases, was positive (level 3 up to 8). Subsequently, the abnormal chest shadows disappeared. However, two months later, 2 pulmonary nodules with the halo sign reappeared in other places. Diagnostic therapy with albendazole was performed for 8 weeks. Mild hepatic impairment emerged during therapy, but it was within the allowed range. Thereafter, the results improved for the imaging findings, eosinophilia, serum IgE level, and specific antibody. The antibody level became negative two months after the treatment had ended. We should consider toxocariasis in the differential diagnosis of migratory nodular shadows with the halo sign on chest computed tomography, and immunoserological testing is useful for the diagnosis.

[Two Cases of Rapidly Progressive Community-acquired Pneumonia Due to Pseudomonas aeruginosa].

Pseudomonas aeruginosa is a significant causative bacterium in hospital-acquired pneumonia and nursing and healthcare-associated pneumonia, but it seems to be rare in community-acquired pneumonia (CAP). We report two cases of severe CAP due to P. aeruginosa. Case 1: A 52-year-old man was referred to our hospital for chest and back pain. He was being treated for diabetes mellitus and had a long history of smoking. Chest images showed consolidation in the right upper lobe. Soon after hospitalization, he developed sepsis shock and died seven hours later. Case 2: A 73-year-old man with a history of heavy smoking was referred to our hospital for right chest pain. Chest images showed right upper lobe pneumonia. Although wide-spectrum antimicrobial agents were administrated, he died ten hours after admission. In both cases, there was a rapid progression to death, despite administration of a broad spectrum of antibiotics and treatment for sepsis. In cases of CAP involving the right upper lobe, the possibility of bacteremia and rapid progress should be considered.

Amrubicin for treating elderly and poor-risk patients with small-cell lung cancer.

BACKGROUND: This study was conducted to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly and poor-risk patients with extensive-disease small-cell lung cancer (ED-SCLC). METHODS: Untreated SCLC patients who were >75 years of age or had a performance status of 2 or more were eligible. Amrubicin (35 or 40 mg/m(2) on days 1-3 every 3 weeks) was administered. RESULTS: Between January 2003 and May 2009, 27 patients were evaluated. The median number of treatment cycles was 4 (1-6). Grade 3 or 4 hematologic toxicities comprised neutropenia (63%), leukopenia (56%), thrombocytopenia (15%), and anemia (19%). Febrile neutropenia was observed in four (15%) patients. No treatment-related deaths occurred. The nonhematologic toxicities were mild. The overall response rate was 70%. Progression-free survival, median survival time, and the 1-year survival rate were 6.6 months, 9.3 months, and 30%, respectively. The 40 mg/m(2) dose was feasible and had a tendency to be more effective than the 35 mg/m(2) dose. CONCLUSIONS: Amrubicin exhibits activity and acceptable toxicities for elderly and poor-risk patients with ED-SCLC in the first-line treatment setting.

Effect of gefitinib on warfarin antithrombotic activity.

BACKGROUND: Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib. METHODS: We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records. RESULTS: Twelve (4.1%) of 296 patients treated with gefitinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (P = 0.0100). CONCLUSION: As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.

Phase I and pharmacologic study of irinotecan and amrubicin in advanced non-small cell lung cancer.

PURPOSE: We conducted a Phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer. PATIENTS AND METHODS: Eleven patients with stage IIIB or IV disease were treated at 3-week intervals with amrubicin (5-min intravenous injection on days 1-3) plus 60 mg/m2 of CPT-11 (90-min intravenous infusion on days 1 and 8). The starting dose of amrubicin was 25 mg/m2, and it was escalated in 5 mg/m2 increments until the maximum tolerated dose was reached. RESULTS: The 30 mg/m2 of amrubicin dose was one dose level above the MTD, since three of the five patients experienced DLT during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the DLT, while thrombocytopenia was only a moderate problem. Amrubicin did not affect the pharmacokinetics of CPT-11, SN-38 or SN-38 glucuronide. Except for one patient, the biliary index on day-1 correlated well with the percentage decrease of neutrophils in a sigmoid Emax model. There were five partial responses among 11 patients for an overall response rate of 45%. CONCLUSION: The combination of amrubicin and CPT-11 seems to be active against non-small cell lung cancer with acceptable toxicity. The recommended dose for Phase II studies is 60 mg/m2 of CPT-11 (days 1 and 8) and 25 mg/m2 of amrubicin (days 1-3) administered every 21 days.

Drug interaction between gefitinib and warfarin.

Gefitinib is a synthetic, oral anilinoquinazoline specifically designed to inhibit the epidermal growth factor receptor tyrosine kinase, and is the first targeted drug to demonstrate reproducible activity in non-small cell lung cancer patients who do not respond to platinum-based chemotherapy. In this report, we present two cases of an interaction between gefitinib and warfarin which has not been reported previously. Because of the potentially serious consequences of this interaction, close monitoring of the International Normalized Ratio and warfarin dosage adjustment are recommended for patients receiving warfarin together with gefitinib.

[New anti-cancer agents--from cytotoxic systemic chemotherapy to target-based agents].

Lung cancer is the leading cause of cancer-related death throughout the world including Japan. During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. To date, clinical research has defined the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) as modern platinum-based doublets considered more efficacious than any single regimen and with no added benefit to triplet therapies. However, we have reached an efficacy plateau with these agents. Rearrangement of the drug combination or change of the drug doses and schedules will not result in significant further progress. New, less toxic agents that improve survival and quality of life are clearly needed. In the last three decades, we have gained a growing understanding of the molecular biologic changes and the complex series of cellular signals that allow cancer cells to manifest behavior. This provides an opportunity to develop novel therapies aimed at inhibiting some of these changes and signals. Targeted agents, primarily the epidermal growth factor receptor inhibitors, have led to a new era in the treatment of NSCLC. This paper will review the current status of cytotoxic agents and molecular targeted therapy in lung cancer potential useful in the treatment of the patients.

Acquired reactive perforating collagenosis in a patient with lung fibrosis.

Reactive perforating collagenosis (RPC) is a rare disorder characterized by the transepidermal elimination of altered collagen. The inherited form of RPC begins in early childhood, but acquired reactive perforating collagenosis (ARPC) begins in adult life. ARPC is associated with diabetes mellitus, renal disease, and malignancy. ARPC with lung fibrosis has not previously been reported in the literature, and the relationship between ARPC and lung fibrosis has not been studied. The etiological relationship between the two disorders appears to be uncertain. Although their association in this case could be due to chance, it may be due to the transforming growth factor beta abnormalities seen in both diseases. In this report, we describe a case of ARPC with lung fibrosis and propose an etiological association between the two diseases.

[Case report of pulmonary epithelioid hemangioendothelioma].

A 45-year-old man was admitted to our hospital because of multiple nodular shadows in the right upper field of a chest radiogram taken at a regular medical checkup. He underwent open lung biopsy. The lung tumor found was diagnosed histologically as pulmonary epithelioid hemangioendothelioma. The tumor cells showed positive staining for CD34 and factor VIII-related antigen. Pulmonary epithelioid hemangioendothelioma (PEH) is a rare lung tumor, of which only 40 cases, including the present case, were reported between 1983 and 2002 in Japan. PEH is a progressive, low-grade malignant tumor that originates from hemangioendothelial cells. In chest radiography or CT scanning, PEH is usually discovered incidentally as multiple nodular shadows. Many cases of PEH are diagnosed by open lung biopsy or thoracoscopic biopsy. No standard therapy for PEH has yet been established, other than resection of a solitary lesion. The present patient has been followed without treatment for five-and-a-half years, and is still alive with no symptoms.