Development of a score model to predict long-term prognosis after community-onset pneumonia in older patients.

BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.

Successful EGFR Mutation Detection in Cytological Specimens of Lung Cancer with Challenging Biopsies by Integrating Virtual Bronchoscopy Navigation and Endobronchial Ultrasound Guidance with Highly Sensitive Next-Generation Sequencing: A Case Report.

Introduction: This case report presents the successful detection of an EGFR exon 19 deletion using virtual bronchoscopic navigation (VBN) and endobronchial ultrasound with guide sheath (EBUS-GS) brushing, integrated with highly sensitive next-generation sequencing (NGS), even in challenging biopsy scenarios. The growing prevalence of driver gene alterations in non-small cell lung cancer necessitates effective bronchoscopic technology and reliable multiplex gene NGS panels. However, data regarding the optimal bronchoscopic techniques when using highly sensitive NGS panels are limited. Herein, we report a case utilizing VBN-guided EBUS-GS brushing as an exploratory approach to address this challenge. Case Presentation: A 71-year-old man was evaluated for a band-like lesion near the left pleura during spinal cord infarction. Transbronchial specimens were obtained from lesions invisible on conventional chest radiography and X-ray fluoroscopy using VBN and EBUS-GS brushing. Cytological brushing specimens revealed lung adenocarcinoma, and highly sensitive NGS identified an EGFR exon 19 deletion. He was diagnosed with stage IB disease and underwent radical radiotherapy owing to his fragile condition. If recurrence occurs, the patient will be treated with an EGFR inhibitor. Conclusion: VBN-guided EBUS-GS brushing, a minimally invasive approach, combined with highly sensitive NGS has the potential to provide accurate molecular diagnoses to more patients with lung cancer, thereby offering opportunities for personalized treatment. Our findings warrant further investigation to determine optimal bronchoscopic technologies for obtaining tumor specimens.

Human Vγ9Vδ2 T cells exhibit antifungal activity against Aspergillus fumigatus and other filamentous fungi.

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis. IMPORTANCE: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.

Novel method of attaching a suction tube externally to a tracheal tube as an insertion route for a Fogarty catheter in cryobiopsy: Retrospective comparative study.

BACKGROUND: Cryobiopsy use is anticipated to become more common in diagnosing lung diseases. In Japan, inserting a Fogarty catheter through a suction channel above the endotracheal tube's cuff for hemostasis is common practice. However, the rigid nature of the endotracheal tube poses challenges to tracheal intubation using a bronchoscope. The endotracheal tube cuff must be removed to prevent interference during Fogarty catheter insertion. To simplify the procedure and enhance safety, we devised and implemented a method of inserting a hemostatic Fogarty catheter with a suction tube externally attached to a softer endotracheal tube. This study aimed to evaluate the sustainability of this Fogarty catheter insertion method using suction tubes. METHODS: The hemostatic Fogarty catheter insertion method was retrospectively validated. We compared outcomes between 60 patients who underwent the conventional method with a suction channel above the cuff and 50 patients who underwent the novel approach with an externally attached suction tube. RESULTS: The physicians performing bronchoscopy and inserting the Fogarty catheter in the group in which the suction tube was externally attached for Fogarty catheter insertion had little experience. However, the overall bronchoscopy time was shorter; the two groups showed no significant differences in complications. CONCLUSION: Regarding cryobiopsy procedures, using an externally attached suction tube for Fogarty catheter insertion was practical and comparable to the conventional method of using a suction channel above the cuff. This method made the procedure more simple and safe.

Platypnoea-orthodeoxia syndrome in COVID-19 pneumonia patients: An observational study.

This retrospective observational study aimed to assess the clinical characteristics of platypnea-orthodeoxia syndrome in patients with coronavirus disease 2019 (COVID-19) treated using mechanical ventilation or high-flow nasal canula. We analyzed 42 consecutive patients with COVID-19 from January 2020 to March 2022. The primary outcomes were the incidence of platypnea-orthodeoxia syndrome, the time with required long-term oxygen therapy, and short-term prognosis. Additionally, we examined the relationships between platypnea-orthodeoxia syndrome and COVID-19 severity, the time with long-term oxygen therapy, and short-term prognosis. Of the 42 included patients, 15 (35.7 %) had platypnea-orthodeoxia syndrome. Although mortality was not significantly different between both groups, the oxygen withdrawal rate in the platypnea-orthodeoxia syndrome group was significantly lower than that in the group without this syndrome. Clinical staff should be aware of the possibility of platypnea-orthodeoxia syndrome during positional changes in patients with COVID-19. Recognizing POS can improve early detection, countermeasures, and safety during physiotherapy.

Risk factor of non-tuberculous Mycobacterium infection in patients with rheumatoid arthritis and other autoimmune diseases receiving biologic agents: A multicenter retrospective study.

BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib.

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.