Comparison of the outcomes of Pneumocystis jirovecii pneumonia in rheumatoid arthritis patients treated with and without biologics.

BACKGROUND: To investigate the outcomes of Pneumocystis jirovecii pneumonia (PCP) between patients with rheumatoid arthritis (RA) treated with and without biologics before PCP onset. PATIENTS AND METHODS: We retrospectively included rheumatoid arthritis (RA) patients with PCP treated with and without biologics before PCP onset. The primary endpoints were 30-day and 180-day survival rates, and the secondary endpoint was severe PCP, including in-hospital death, intensive care unit admission, and requirement of respiratory support during hospitalization. RESULTS: Eighty-two patients were enrolled in this study, including the Biologics group (n = 39) and Non-Biologics group (n = 43). There were no significantly differences in the 30-day and 180-day survival rates and severe PCP rate in the Biologics group and the Non-Biologics group before and after adjusting the patient characteristics. Kaplan-Meier survival curves for death showed no significantly differences between the Biologics and Non-Biologics groups. Cox regression hazard analysis revealed that the average daily prednisolone dose within 90 days before PCP onset was weakly associated with mortality after PCP. CONCLUSIONS: Biologic use before PCP onset did not increase the severity and mortality of PCP compared to non-biologics use in patients with RA.

Predictors of improvement of radial-endobronchial ultrasonography findings from "adjacent to" to "within" in endobronchial ultrasonography using a guide sheath: a retrospective cohort study.

Background: In flexible bronchoscopy, endobronchial ultrasonography using a guide sheath (EBUS-GS) has varying diagnostic yield depending on the findings of radial-endobronchial ultrasonography (R-EBUS). The diagnosis rate is lower when the ultrasound probe is "adjacent to", than when it is "within" the lesion. However, these findings are inconsistent, and the imaging status may change from "adjacent to" to "within" as examination progresses. In this study, we analyzed the predictive factors for this change, which remain unexplored till date. Methods: Patients who underwent flexible bronchoscopic biopsy with EBUS-GS at Kameda Medical Centre between 1 April 2014 and 31 March 2019 were included in this retrospective cohort study. Patients without "adjacent to" lesions were excluded. The appearance of "A to W" (the change from "adjacent to" to "within" imaging status) was the primary outcome. Based on multivariate regression and receiver operating characteristic curve analysis, we evaluated the discriminative properties of the factors strongly correlated with "A to W". Results: In total, 260 patients were included in this study. In 84 cases, the R-EBUS findings were "A to W". No such findings were observed in 176 cases. The mean lesion diameter was significantly larger (P=0.021) in the group with "A to W" than in the group without. The odds ratio [1.023 (1.003-1.046)] for lesion diameter showed statistical significance in the multivariable regression model. The sensitivity and specificity were 0.346 and 0.852, respectively, at the optimal threshold (29.25 mm) set using the Youden index. Conclusions: We found that lesion diameter was a significant factor in predicting "A to W", with a cut-off value of 29.25 mm and high specificity (0.852).

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. RESEARCH QUESTION: What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? STUDY DESIGN AND METHODS: In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. RESULTS: Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/d in the low-dose group and 17.78 mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs 18.4%, respectively; P = .080) or 180-day mortality (14.6% vs 26.1%, respectively; P = .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs 59.0%, respectively; P = .005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P = .158), respectively. INTERPRETATION: Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

Empyema and bacteremia caused by Parvimonas micra: A case report.

Parvimonas micra is a gram-positive anaerobic coccus (GPAC) that colonizes the oral cavity and gastrointestinal tract. Recent advances in bacterial identification have confirmed the clinical importance of Parvimonas micra. Here, we report a case of empyema with bacteremia caused by Parvimonas micra. We successfully treated the patient with the appropriate antibiotics and drainage. Parvimonas micra can cause respiratory infections, including empyema, which can progress to bacteremia if treatment is delayed. In Parvimonas micra infections, not only the oral cavity but also the entire body must be investigated to clarify the entry mechanism.

Immunogenicity and safety of influenza vaccine in patients with lung cancer receiving immune checkpoint inhibitors: A single-center prospective cohort study.

INTRODUCTION: Patients with lung cancer have a high risk of influenza complications. International guidelines recommend annual influenza vaccination for patients with cancer. Immune checkpoint inhibitors (ICIs) are progressively used to treat lung cancer. Data regarding immunogenicity and safety of influenza vaccine are limited in patients with lung cancer receiving ICIs; therefore, we conducted this single-center, prospective observational study in the Japanese population. METHODS: Patients with lung cancer receiving ICIs and influenza immunization were enrolled. Blood samples were collected from patients for serum antibody titer measurement pre- and 4 ± 1 weeks post-vaccination. The primary endpoint was seroprotection rate (sP) at 4 ± 1 weeks post-vaccination. The secondary endpoints were geometric mean titer (GMT), mean fold rise, seroresponse rate (sR), seroconversion rate (sC), and immune-related adverse events (irAEs), defined as adverse effects caused by ICI administration, 6 months post-vaccination. RESULTS: Influenza vaccination in the 23 patients included in the immunogenicity analyses significantly increased GMT for all strains, and sP, sR, and sC were 52%-91%, 26%-39%, and 26%-35%, respectively. In the 24 patients included in the safety analyses, 7 (29%) and 5 (21%) patients exhibited systemic and local reactions, respectively. Only one patient (4%) (hypothyroidism, grade 2) showed post-vaccination irAEs. CONCLUSIONS: Overall, influenza vaccination in patients with lung cancer receiving ICIs showed acceptable immunogenicity and safety, thus supporting annual influenza vaccination in this population.

Nodule-type pneumonitis mimicking lung abscess or tumor recurrence on chest computed tomography identified as osimertinib-induced pneumonitis: A case report.

Osimertinib-induced pneumonitis usually manifests as ground glass opacities (GGO) on chest computed tomography (CT) scans. Here, we encountered a case involving a 42-year-old woman who had nodule-type pneumonitis mimicking lung abscess or tumor recurrence caused by osimertinib. When a nodular pattern is seen on the chest CT scan of a patient receiving osimertinib treatment, drug-induced pneumonitis should be considered as a differential diagnosis. To the best of our knowledge, this is the first case of osimertinib-induced pneumonitis that manifested as a nodule-type pneumonitis mimicking lung abscess or tumor recurrence on chest CT scan.

Simultaneous treatment for M ycobacterium-avium complex lung disease and allergic bronchopulmonary aspergillosis: A case report.

Recently, there are several reports of simultaneous allergic bronchopulmonary aspergillosis (ABPA) and Mycobacterium-avium complex (MAC) lung disease. However, the strategies for early diagnosis and appropriate treatment for patients with both ABPA and MAC lung disease have not been established. Here, we report a case with ABPA complicated by MAC lung disease, which was successfully diagnosed and treated by simultaneous administration of systemic steroids and antimycobacterial drugs. Bronchoscopy can be useful in the diagnosis of such cases. Furthermore, in a patient with concurrent ABPA and MAC lung disease, simultaneous treatments for both diseases could reduce both diseases.

Long-term survival of a patient with uterine cancer-induced pulmonary tumor thrombotic microangiopathy following treatment with platinum-based chemotherapy and bevacizumab: A case report.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal cancer-related disease. Owing to its non-specific findings, aggressive course, and lack of established treatment guidelines, only a few cases of antemortem diagnosis in long-term survivors have been reported. We aimed to report a case of uterine cervical cancer induced PTTM that was suspected based on pulmonary hypertension and successfully treated using combination chemotherapy despite of delayed diagnose. It is important to be aware that PTTM should be suspected when respiratory failure occurs in patients with unexplained pulmonary hypertension. Multidisciplinary treatments including molecular targeted therapies might be effective treatment options.

The TAR-RNA binding protein is required for immunoresponses triggered by Cardiovirus infection.

LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5. siRNA knockdown experiments indicate that TRBP is important for Cardiovirus-triggered interferon responses, but TRBP is not involved in Sendai virus-triggered interferon response that is mediated mainly by RIG-I. To support functional interaction with LGP2, overexpressed TRBP increased Cardiovirus-triggered interferon promoter activity only when LGP2 and MDA5 are co-expressed but not MDA5 alone. Together, our findings illustrate a possible connection between an RNAi-regulatory factor and antiviral RNA recognition that is specifically required for a branch of the virus induced innate immune response.