Urinary Retention Suggesting Aseptic Meningitis: Meningitis-Retention Syndrome Without Physical Signs of Meningeal Irritation.

Meningitis-retention syndrome (MRS) is the combination of aseptic meningitis and acute urinary retention that occurs in the absence of other neurological diseases. The cause(s) of MRS remain unclear. A 57-year-old Japanese woman was referred to our hospital for the evaluation of persistent fever and headache. The fever's cause was initially unclear, but the presence of urinary retention raised concern about possible aseptic meningitis despite no physical indications of meningeal irritation. Only typical cases of MRS have been reported thus far to our knowledge, and it is important that clinicians are aware of MRS when it presents in this atypical form.

Atezolizumab for Pretreated Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonia: Final Analysis of Phase II AMBITIOUS Study.

BACKGROUND: Interstitial pneumonia (IP) is a poor prognostic comorbidity in patients with non-small cell lung cancer (NSCLC) and is also a risk factor for pneumonitis. The TORG1936/AMBITIOUS trial, the first known phase II study of atezolizumab in patients with NSCLC with comorbid IP, was terminated early because of the high incidence of severe pneumonitis. METHODS: This study included patients with idiopathic chronic fibrotic IP, with a predicted forced vital capacity (%FVC) of >70%, with or without honeycomb lung, who had previously been treated for NSCLC. The patients received atezolizumab every 3 weeks. The primary endpoint was the 1-year survival rate. RESULTS: A total of 17 patients were registered; the median %FVC was 85.4%, and 41.2% had honeycomb lungs. The 1-year survival rate was 53.3% (95% CI, 25.9-74.6). The median overall and progression-free survival times were 15.3 months (95% CI, 3.1-not reached) and 3.2 months (95% CI, 1.2-7.4), respectively. The incidence of pneumonitis was 29.4% for all grades, and 23.5% for grade ≥3. Tumor mutational burden and any of the detected somatic mutations were not associated with efficacy or risk of pneumonitis. CONCLUSION: Atezolizumab may be one of the treatment options for patients with NSCLC with comorbid IP, despite the high risk of developing pneumonitis. This clinical trial was retrospectively registered in the Japan Registry of Clinical Trials on August 26, 2019, (registry number: jRCTs031190084, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084).

Pembrolizumab in advanced NSCLC patients with poor performance status and high PD-L1 expression: OLCSG 1801.

BACKGROUND: The role of pembrolizumab in the treatment of poor performance status (PS) patients remains unclear. PATIENTS AND METHODS: We conducted a phase II trial to investigate the efficacy and safety of pembrolizumab as first-line therapy for non-small-cell lung cancer (NSCLC) patients with PSs of 2-3 and programmed cell death ligand 1 (PD-L1) expression ≥ 50%. The primary endpoint of this study was the objective response rate (ORR). RESULTS: Fourteen patients treated at eight institutions were enrolled. Most patients had PS 2 (12/14; 86%) and others had PS 3 (2/14; 14%). The ORR was 57.1% (95% confidence interval 28.9-82.3%), which met the primary endpoint. The median progression-free survival (PFS) and 1-year PFS rates were 5.8 months and 20.0%, respectively. At the time of data cut-off, one patient had received treatment for more than 1 year; another patient had received treatment for more than 2 years. Nine patients had improved PS with treatment (Wilcoxon signed-rank test, p = 0.003). Two patients had immune-related adverse events ≥ grade 3: grades 5 and 3 elevation in alanine and aspartate aminotransferases. Two PS 3-stage patients were diagnosed with clinically progressive disease prior to initial computed tomography; both died within 2 months. CONCLUSION: Pembrolizumab was effective for the treatment of NSCLC patients with a poor PS and PD-L1 level ≥ 50%. However, given the poor outcomes of the PS 3 patients, the drug is not indicated for such patients. Adverse events, including liver dysfunction, should be carefully monitored. REGISTRATION ID: UMIN000030955.

Characteristics of patients with EGFR-mutant non-small-cell lung cancer who benefited from immune checkpoint inhibitors.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are less effective in non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. However, a small percentage of patients with EGFR-mutant NSCLC do respond, and the characteristics of these patients are not known. Here, we identify the characteristics of patients who may respond to ICI therapy for EGFR-mutant NSCLC. PATIENTS AND METHODS: The medical records of NSCLC patients with EGFR mutations who received PD-1/PD-L1 antibody monotherapy at nine institutions were reviewed. RESULTS: In total, 58 patients with EGFR-mutant NSCLC were analyzed. Various clinical factors such as smoking history and EGFR mutation type were not associated with progression-free survival (PFS) of ICIs, while the PFS of prior EGFR tyrosine kinase inhibitors (TKIs) was inversely associated with that of ICIs. Patients who responded to prior EGFR TKIs for > 10 months exhibited a significantly shorter response to ICIs compared to those who had responded for ≤ 10 months (PFS of ICI: 1.6 vs. 1.9 months; hazard ratio: 2.54; 95% confidence interval 1.26-5.12; p = 0.009). However, patients who responded to ICIs for > 6 months responded to prior EGFR TKIs for significantly shorter periods compared to those who responded to ICIs for ≤ 6 months (PFS of prior EGFR TKI: 5.3 vs. 12.1 months; log-rank test: p = 0.0025). CONCLUSION: The duration of response to prior EGFR TKIs could be a predictive marker of ICI therapy in EGFR-mutant NSCLC patients.

Phase II study of amrubicin plus erlotinib in previously treated, advanced non-small cell lung cancer with wild-type epidermal growth factor receptor (TORG1320).

Background Amrubicin (AMR) is a completely synthetic 9-aminoanthracycline and clinically active against non-small cell lung cancer (NSCLC). We conducted a phase I study of AMR and erlotinib (ERL) combination therapy in previously treated patients with advanced NSCLC and have already reported the safety and effectiveness. Methods We conducted a multi-center, single-arm phase II trial to evaluate the efficacy of AMR and ERL combination therapy in patients with previously treated, advanced NSCLC harboring wild-type EGFR, PS 0-1 and < 75 years of age. Patients were treated at 3-week intervals with AMR plus ERL. The primary endpoint was the PFS, and the secondary endpoints were the response rate (RR), disease control rate (DCR), overall survival (OS) and toxicity. The trough ERL concentration (Ctrough) was measured as an exploratory study to analyze the relationship between the efficacy/safety and pharmacokinetics. Results From June 2013 to July 2016, 25 patients were enrolled in this trial. The PFS according to the central test was 3.6 months (95% confidence interval 2.1-5.1). The RR and DCR were 24.0% and 64.0%, respectively. We had no treatment-related deaths in this study. Conclusions The PFS of AMR and ERL combination therapy was superior to that of AMR monotherapy in the historical setting, but the primary endpoint was not met in this trial. In our study, the pharmacokinetic analysis showed that the Ctrough of ERL was elevated with combination therapy. This combination therapy might be a viable treatment for previously treated NSCLC patients without a driver oncogene mutation. Clinical trial information UMIN 000010582.

Impact of previous thoracsic radiation therapy on the efficacy of immune checkpoint inhibitors in advanced non-smasll-cell lung cancer.

OBJECTIVES: Studies investigating the association between radiation therapy and the efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer have provided inconsistent results, likely due to relatively small cohort sizes. This study investigated the effect of previous thoracic radiation therapy on the efficacy of immune checkpoint inhibitor therapy in a large non-small-cell lung cancer cohort. PATIENTS AND METHODS: We conducted a retrospective cohort study using data from 531 non-small-cell lung cancer patients who received monotherapy with programmed cell death protein 1/programmed death-ligand 1 inhibitors at nine institutions. The effects of thoracic radiation therapy on the efficacy of immune checkpoint inhibitors were investigated. RESULTS: A total of 531 non-small-cell lung cancer patients treated with immune checkpoint inhibitors were included in this study. The progression-free survival period was significantly longer in patients that had received thoracic radiation therapy before immune checkpoint inhibitor therapy compared to those without previous thoracic radiation therapy (median progression-free survival 5.0 vs. 3.0 months, P = 0.0013). A multivariate analysis showed that thoracic radiation therapy was an independent predictive factor of improved progression-free survival (hazard ratio of progression-free survival: 0.79, P = 0.049). In contrast, extra-thoracic radiation therapy was associated with inferior outcomes (median progression-free survival 3.0 vs. 4.2 months, P = 0.0008). CONCLUSION: Previous thoracic radiation therapy, but not prior extra-thoracic radiation therapy, enhanced the efficacy of anti-programmed cell death protein 1/programmed death-ligand 1 therapy in non-small-cell lung cancer patients.

A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401.

BACKGROUND: Radiation esophagitis is a critical adverse event that needs to be appropriately managed while administering thoracic irradiation. This trial aimed to investigate whether sodium alginate has preventative effects on esophagitis in patients with non-small-cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy (CRT). METHODS: Patients with untreated stage III NSCLC who were eligible for concurrent CRT were randomly assigned at a 1:1:1 ratio to receive one of the following treatments: initial or late use of oral sodium alginate (arms A and B) or water as control (arm C). The primary endpoint was the proportion of patients developing G3 or worse esophagitis. RESULTS: Overall, 94 patients were randomly assigned between February 2014 and September 2018. The study was prematurely terminated because of slow accrual. The proportions of patients with G3 or worse esophagitis were 12.5%, 9.8%, and 19.4% in arms A, B, and C, respectively. Patients receiving sodium alginate had fewer onsets of G3 esophagitis; however, differences compared with arm C were not significant (A vs. C: p = 0.46; B vs. C: p = 0.28). The rates of grade 3 or worse non-hematologic toxicities besides esophagitis were 29%, 26%, and 43% in arms A, B, and C, respectively. Interestingly, compared with arm C, a low rate of febrile neutropenia was observed in arm A (3.1% vs. 19.4%: p = 0.04). CONCLUSIONS: Sodium alginate did not show significant preventative effects on radiation-induced esophagitis in patients with NSCLC. The frequency of CRT-induced febrile neutropenia was lower in the early use sodium alginate arm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier Registry number: UMIN000013133.

Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status.

Most clinical trials of non-small-cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI-treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression-free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0-1 patients (median PFS, 4.1 vs 2.0 months; P < .001 and median OS, 17.4 vs 4.0 months; P < .001). Among NSCLC patients with programmed cell death protein-ligand 1 (PD-L1) expression of 50% or higher who were treated with pembrolizumab as first-line therapy, the median PFS times of patients with PS 2 and 0-1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0-1 (P = .321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first-line treatment in NSCLC patients expressing high levels of PD-L1 could provide a clinical benefit, even in patients with PS 2.

Updated Survival Data for a Phase I/II Study of Carboplatin plus Nab-Paclitaxel and Concurrent Radiotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer.

LESSONS LEARNED: Updated survival data for a phase I/II study of carboplatin plus nab-paclitaxel and concurrent radiotherapy were collected. In the group of 58 patients who were enrolled at 14 institutions in Japan, the median overall survival was not reached and the 2-year overall survival rate was 66.1% (95% confidence interval, 52.1%-76.8%). Results reveal encouraging feasibility and activity for this regimen. BACKGROUND: We report the updated survival data for a phase I/II study of carboplatin plus nab-paclitaxel (nab-P/C) and concurrent radiotherapy (CRT) in patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: Individuals between 20 and 74 years of age with unresectable NSCLC of stage IIIA or IIIB and a performance status of 0 or 1 were eligible for the study. Patients received weekly nab-paclitaxel at 50 mg/m2 for 6 weeks together with weekly carboplatin at an area under the curve (AUC) of 2 mg/ml/min and concurrent radiotherapy with 60 Gy in 30 fractions. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel (100 mg/m2 on days 1, 8, and 15) plus carboplatin (AUC of 6 on day 1). After the treatment, patients were observed off therapy. The primary endpoint of the phase II part of the study was progression-free survival (PFS). RESULTS: Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. At the median follow-up time of 26.0 months (range, 4.0-49.6 months), the median overall survival (OS) was not reached (95% confidence interval [CI], 25.3 months to not reached) and the 2-year OS rate was 66.1% (95% CI, 52.1%-76.8%). The median PFS was 11.8 months (95% CI, 8.2-21.0 months), and the 2-year PFS rate was 35.9% (95% CI, 23.1%-48.9%). Subgroup analysis according to tumor histology or patient age revealed no differences in median PFS or OS. Long-term follow-up of toxicities did not identify new safety signals, and no treatment-related deaths occurred during the study period. CONCLUSION: Concurrent chemoradiation with nab-P/C was safe and provided a long-term survival benefit for patients with locally advanced NSCLC.

Percutaneous transcatheter closure of high-risk patent foramen ovale in the elderly.

The efficacy of percutaneous transcatheter closure for preventing recurrent cerebrovascular events in elderly patients with high-risk patent foramen ovale (PFO) remains unclear, whereas in young patients, it has been shown to effectively prevent the recurrence of embolic stroke. The aim of this study was to investigate the safety and efficacy of percutaneous PFO closure in elderly patients with high-risk PFO. Between September 2012 and October 2018, 14 patients ≥ 60 years old with high-risk PFO underwent percutaneous closure to prevent recurrence of cerebrovascular events. The primary end point was recurrence of cerebrovascular events after closure in elderly patients with high-risk PFO, and the secondary end points were occurrence of device-related complications, cerebral hemorrhage, and new-onset atrial fibrillation (AF). The mean patient age and number of cerebrovascular events before closure were 75.2 ± 6.5 years and 1.7 ± 0.7, respectively. All procedures were successfully performed under general anesthesia by transesophageal echocardiography and using a 25-mm Amplatzer Cribriform device. No procedure-related complications occurred. Patients were followed up for a mean 2.6 ± 1.8 years. No patients experienced device-related complications or recurrent cerebrovascular events. However, one patient had AF-related device closure complications at 1 month postoperatively. In addition, other patient had a cerebral hemorrhage with unknown relationship to PFO closure 3 years postoperatively. Percutaneous closure of high-risk PFO in elderly patients may be as effective and safe as in younger patients. It is crucial to evaluate PFO morphology regardless of age in cases of paradoxical embolism.

Correction to: Percutaneous transcatheter closure of high-risk patent foramen ovale in the elderly.

In the original publication of the article, the below sentence were garbled.

Outcomes of mitral valve transcatheter edge-to-edge repair for patients with hemodynamic instability: A systematic review and meta-analysis.

BACKGROUND: The outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) for the patients with severe mitral regurgitation (MR) in hemodynamically unstable conditions, such as cardiogenic shock, still remain unclear. We aimed to integrate previous publications regarding M-TEER indicated for life-threatening conditions and indirectly particularly compared the short-term outcomes thereof, with that of other treatments. METHODS: We systematically searched the PubMed, Cochrane, and MEDLINE databases for studies from inception to June 2023, regarding M-TEER in patients with hemodynamic instability and severe MR. The primary outcomes analyzed included the in-hospital and 30-day mortality rates, and peri-procedural complications. RESULTS: Of the initial 820 publications, we conducted a meta-analysis of a total of 25 studies. The relative risk of moderate-to-severe or severe MR was 0.13 (95 % confidence interval [CI]: 0.10-0.18, I2 = 45.2 %). The pooled in-hospital and 30-day mortality rates were 11.8 % (95 % CI: 8.7-15.9, I2 = 96.4 %) and 14.1 % (95 % CI: 10.9-18.3, I2 = 35.5 %), respectively. The 30-day mortality rate was statistically significantly correlated with the residual moderate-to-severe or severe MR, as per the meta-regression analysis (coefficient ß = 3.48 [95 % CI: 0.99-5.97], p = 0.006). Regarding peri-procedural complications, the pooled rates of a stroke or transient ischemic attack, life-threatening or major bleeding, acute kidney injury, and peri-procedural mitral valve surgery were 2.3 % (95 % CI: 1.9-2.6), 7.6 % (95 % CI: 6.8-8.5), 32.9 % (95 % CI: 31.6-34.3), and 1.0 % (95 % CI: 0.8-1.3), respectively. CONCLUSIONS: This meta-analysis demonstrates that the relatively higher rates of procedural complications were observed, nevertheless, M-TEER can potentially provide favorable short-term outcomes even in hemodynamically unstable patients. PROSPERO REGISTRATION NUMBER: CRD42023468946.

A Phase â ¡ Study of Ubenimex Combined With Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small-Cell Lung Cancer: TORG2241 (UBE-Q).

BACKGROUND: According to the results of the KEYNOTE-407 trial, pembrolizumab plus platinum-based chemotherapy is the standard of care for patients with previously untreated advanced squamous non-small-cell lung cancer (NSCLC). Ubenimex, a potent aminopeptidase inhibitor, is an oral drug with immunostimulatory and antitumor activities. We aim to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. PATIENTS AND METHODS: This prospective, single-arm, multicenter, phase II clinical trial is conducted to confirm the tolerability and efficacy of the tested drugs. Patients with previously untreated advanced squamous NSCLC will receive a predetermined daily dose of ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex will begin at level 1 (30 mg), which will be increased to levels 2 (60 mg) and 3 (120 mg) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level will be analyzed. The primary endpoint of the efficacy evaluation will be the objective response rate assessed by an independent review committee. CONCLUSIONS: This is the first study to evaluate the efficacy and safety of ubenimex combined with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. The results will help devise future treatment strategies.

Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non-Small Cell Lung Cancer.

Importance: Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older. Objective: To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC. Design, Setting, and Participants: This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022. Exposures: Systemic therapy. Main Outcomes and Measures: The main outcomes were overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03). Conclusions and Relevance: In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.

Phase II Study of Durvalumab Immediately after Completion of Chemoradiotherapy in Unresectable Stage III Non-small Cell Lung Cancer: TORG1937 (DATE Study).

PURPOSE: Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation for up to 12 months is the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, exactly when to initiate durvalumab therapy after chemoradiation completion remains unknown. We evaluated the efficacy and safety of durvalumab, administered immediately after CCRT completion, for patients with unresectable stage III NSCLC. PATIENTS AND METHODS: This study was a prospective, single-arm, open-label phase II clinical trial. Patients without disease progression after definitive CCRT (two cycles of platinum-based doublet chemotherapy with 60 Gy/30 Fr radiotherapy) received durvalumab (every 2 weeks for up to 12 months) from the next day (up to 5 days) after the final radiation dose. The primary endpoint was the 1-year progression-free survival (PFS) from registration before the start of CCRT. RESULTS: From January 2020 to August 2020, 47 of 50 enrolled patients were evaluable for treatment efficacy and safety. The 1-year PFS from registration was 75.0% [60% confidence interval (CI), 69.0-80.0 and 95% CI, 59.4-85.3]. The objective response rate throughout the study treatment and median PFS from registration were 78.7% and 14.2 months (95% CI, 13.4 to not reached), respectively. Grade 3/4 pneumonitis and febrile neutropenia were each 4.3%. CONCLUSIONS: Our study met the primary endpoint. The incidence of pneumonitis was similar to that of a Japanese subset in the PACIFIC study. Our data support the efficacy and safety of durvalumab administered immediately after the completion of CCRT for patients with unresectable stage III NSCLC.

Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101).

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.

Septic pulmonary embolism induced by dental infection.

Dental infection can be an important source for septic pulmonary embolism (SPE), but only a few cases of SPE accompanying dental infection have been reported. The aim of this study was to characterize the clinical features of SPE induced by dental infection. Patients who fulfilled the diagnostic criteria described in the text were recruited in a retrospective fashion. All 9 patients were men, with a median age of 59 years (range:47 to 74 years). Eight patients had chest pain (88.9%), 5 had a preceding toothache (55.6%) and 3 had preceding gingival swelling (33.3%). Blood cultures obtained from 7 patients were negative. Periodontitis was found in all of the cases, periapical periodontitis in 5 cases, and gingival abscess in 3 cases. The median duration of hospitalization was 15 days, and symptoms were mild in some cases. In addition to antimicrobial therapy, tooth extraction was performed in 3 cases, tooth scaling in 6. SPE induced by dental infection has prominent clinical characteristics such as male preponderance, chest pain, preceding toothache, and mild clinical course.

Corsair rotational bougie technique for facilitating balloon passage through a total occlusion lesion: a case report of balloon pulmonary angioplasty.

A 77-year-old man presented with dyspnoea and was diagnosed with chronic thromboembolic pulmonary hypertension. Balloon pulmonary angioplasty was attempted; however, the balloons could not be advanced to the total occlusion lesion in the right A3 segment. The obstruction was overcome using a microcatheter Corsair (AsahiKASEI). This technique may be useful in managing a total occlusion lesion.