High level of C-reactive protein as a predictive factor for immune-related adverse events of immune checkpoint inhibitors in non-small cell lung cancer: a retrospective study.

Background: Several risk factors for the immune-related adverse events (irAEs) during treatment with immune checkpoint inhibitors (ICIs) have been reported, of which include high levels of C-reactive protein (CRP). In this study, we aim to evaluate CRP levels before ICIs treatments as potential predictive biomarkers of irAEs incidence rate and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: Between December 1, 2015 to December 31, 2019, we retrospectively collected all adult patients with NSCLC who received at least one dose of an ICI targeting the PD-1/PD-L1 axis at the Iwate Medical University Hospital in Japan. In this study the patients were categorized into low and high groups with a cut-off value of 10 mg/L as the baseline level of CRP before the ICI treatment. The primary endpoint was relationship between CRP levels at baseline and incidence of irAEs. The secondary endpoints were the relationship of progression-free survival (PFS) and OS. Results: A total of 101 irAEs, and 25 severe irAEs were observed. The incidence of the most irAEs was higher in the high CRP group compared to the low CRP group (54.4% vs. 34.5%, respectively, P=0.003). The most frequent irAEs were skin rush (28.8%), followed by pneumonitis (19.2%), hypothyroidism (15.4%), and hepatotoxicity (9.6%). The most common grade 3 or 4 irAEs was pneumonitis (7.9%), which tended to be more frequent in the high CRP group. In multivariate analysis, patients with high CRP levels had an adjusted OR of 2.41 and were associated with an increased risk of developing irAEs (95% CI: 1.16-4.43, P=0.020). The high CRP group was related with shorter PFS compared to the low CRP group (2.2 vs. 3.3 months, respectively, P=0.006). The high CRP group were also related with shorter OS compared to the low CRP group (8.9 vs. 39.1 months, respectively, P<0.001). Conclusions: The results suggest that higher level of pretreatment CRP is involved in the development of irAE and poor prognosis. Identification of patients at high risk of irAEs would be of great help. Future multicenter prospective studies are needed to expand on this study.

A randomized trial to evaluate the preventive effect of lafutidine on chemotherapy-induced peripheral neuropathy in patients treated with carboplatin and paclitaxel for lung cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) has a significant impact on the therapeutic efficacy of chemotherapy and patients' quality of life. The aim of this study was to assess the preventive effect of lafutidine on CIPN. METHODS: Patients were randomly assigned (1:1) to carboplatin and paclitaxel chemotherapy with lafutidine 10 mg twice daily (lafutidine group) or without lafutidine (control group). Peripheral neuropathy in both groups was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and two patient-based questionnaires, the Patient Neurotoxicity Questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx). The primary outcome was the incidence of grade 2 or higher peripheral neuropathy in CTCAE version 5.0. The target number of cases was set at approximately 40. RESULTS: In total, 18 patients were screened, and 16 patients were assigned to the lafutidine group (n=9) or control group (n=7) between January 2021 and January 2023. Due to poor recruitment, the target number of cases was not reached. Grade 2 or higher neuralgia was 22.2% in the lafutidine group and 14.3% in the control group. Grade 2 or higher peripheral sensory neuropathy was 100% in the lafutidine group and 71.4% in the control group (P=0.175). Grade 3 or higher peripheral neuropathy was not detected in either group. There was no significant difference in PNQ scores between the two groups. Median FACT/GOG-Ntx scores after the fourth cycle tended to be lower in the lafutidine group than in the control group. There was no statistically significant difference in progression free survival (PFS) between the two groups. There were no adverse events due to lafutidine administration. CONCLUSIONS: Although the preventive effect of lafutidine on CIPN could not be demonstrated statistically, lafutidine FACT/GOG-Ntx scores showed a trend toward decreased neurotoxicity as chemotherapy proceeded. More reliable studies using lafutidine on the prevention of CIPN should be conducted. TRIAL REGISTRATION: Japan Registry of Clinical Trials, identifier: jRCTs021200031.

Efficacy and Effectiveness of Showerheads Attached with Point-of-use (POU) Filter Capsules in Preventing Waterborne Diseases in a Japanese Hospital.

Tap water contamination is a growing concern in healthcare facilities, and despite chlorination, tap water in these facilities contains several pathogenic microorganisms causing healthcare-associated waterborne infections or nosocomial outbreaks. Shower units are particularly prone to contamination as they are conducive for bacterial growth and can even produce bioaerosols containing pathogenic bacteria. Shower units coupled with point-of-use (POU) water filters are a simple and safe option; however, their efficacy has been under-reported. Therefore, we determined the efficacy of showerheads attached with a POU filter capsule in preventing infections in our hospital. We investigated the presence of pathogenic bacteria in water sampled from three shower units. After replacing the original shower units with new ones incorporated with a sterile-grade water filter capsule (0.2 µm; QPoint™), the water samples were analyzed for up to 2 months. The POU filters removed several pathogenic bacteria (Mycobacterium, Pseudomonas, Stenotrophomonas, Aeromonas, and Klebsiella spp.). Filter effectiveness depends on regional water quality and we believe that effective tap water treatment combined with the use of POU filters (introduced at a reasonable cost in healthcare facilities) can considerably minimize waterborne diseases in hospitals and improve patient care.

Changes in pulmonary function of residents in Sanriku Seacoast following the tsunami disaster from the Great East Japan Earthquake.

BACKGROUND: Residents in the district struck by the Great East Japan Earthquake Tsunami (GEJET) suffered from adverse living conditions and various pulmonary diseases. OBJECTIVES: To evaluate the influence of GEJET, we performed serial assessment of pulmonary function of approximately 10,000 residents in the district struck by GEJET. METHODS: Using a spirometer, we assessed the pulmonary function of approximately 10,000 residents older than 18 years in the Sanriku seacoast, which was struck by the tsunami. Measurements were performed in 2011 and 2012. RESULTS: We compared FVC (forced vital capacity) % pred. and FEV1 (forced expiratory volume in 1second) % pred. of subjects between 2011 and 2012, by serial spirometry. Of the 7053 subjects studied, including 2611 men and 4442 women, FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011. Physical indices including height, body weight and the body mass index (BMI) did not change significantly during this period. Smoking prevalence changed significantly between 2010, 2011, and 2012. Both FVC% pred. and FEV1% pred. of subjects who had quit smoking increased significantly on spirometry carried out in 2012, compared with those in 2011. CONCLUSIONS: The pulmonary function expressed as FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011 among the subjects studied. The changes in the smoking status may be one of the reasons for the increase in values observed. However, other undetermined factors during recovery from a disaster might have resulted in improved pulmonary function.

Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan.

Many victims of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011 developed systemic disorders owing to aspiration pneumonia. Herein, we report a case of tsunami lung wherein Scedosporium aurantiacum was detected in the respiratory tract. A magnetic resonance image of the patient's head confirmed multiple brain abscesses and lateral right ventricle enlargement. In this case report, we describe a potential refractory multidrug-resistant infection following a tsunami disaster.