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Background: Because of limitations in previous randomised controlled trials and observational studies, the effectiveness of immediate video-assisted thoracoscopic surgery (VATS) for patients with empyema in real-world settings remains unclear. Objective: This study aimed to evaluate whether immediate VATS improves clinical outcomes in patients with empyema. Methods: This multicentre retrospective cohort study included 744 patients with physician-diagnosed empyema from six hospitals between 2006 and 2021. The exposure was VATS performed within 3 days of empyema diagnosis, the primary outcome was 30-day mortality, and secondary outcomes were 90-day mortality, length of hospital stay, and time from diagnosis to discharge. We used propensity score weighting to account for potential confounders. For outcome analyses, we used logistic regression for mortality outcomes and gamma regression for the number of days. Results: Among the 744 patients, 53 (7.1%) underwent VATS within 3 days, and 691 (92.9%) initially received conservative treatment. After propensity score weighting, the differences in 30- and 90-day mortalities between the immediate VATS and initial conservative treatment groups were 1.18% (95% confidence interval [CI], −10.7 to 13.0%) and −0.08% (95% CI, −10.3 to 10.2%), respectively. The differences in length of hospital stay and time from diagnosis to discharge were −3.22 (95% CI, −6.19 to −0.25 days) and −5.04 days (95% CI, −8.19 to −1.90 days), respectively. Conclusions: Our real-world study showed that immediate VATS reduced the length of hospital stay and the time from diagnosis to discharge. Considering the small sample and differences in protocols between countries, further large-scale studies are warranted. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to assess the association between physical frailty and clinical outcomes among older patients hospitalized for pneumonia. Methods: This study examined 852 consecutive patients hospitalized for pneumonia between October 2018 and September 2020. Patients who were <65 years old, scheduled for admission, did not receive inpatient rehabilitation, or died during admission were excluded. A short physical performance battery (SPPB) test was performed by physical therapists upon discharge. The primary outcome measure was a composite endpoint of readmission or mortality due to any cause within 6 months of discharge. Results: In total, 521 patients (median age, 80 years; interquartile range, 74–86 years) were included in the analyses, and were divided into the following two groups: robust group with SPPB scores >9 (n = 150), and physical frailty group with SPPB scores ≤9 (n = 371). Of these, 346 (66.4%) patients were men; and the median SPPB score was 6 (interquartile range, 1–10). During the median follow‐up period of 53 days (interquartile range, 4–180 days), 92 (17.6%) patients were readmitted and 25 (4.8%) patients died. Patients with physical frailty were at an increased risk for the primary endpoint (hazard ratio, 2.21; 95% confidence interval, 1.44–3.41; P < 0.001); the risk remained significant after adjusting for multiple variables (adjusted hazard ratio, 1.70; 95% confidence interval, 1.05–2.74; P = 0.028). Conclusions: Among older patients with pneumonia, physical frailty status at discharge was an independent risk factor for readmission and mortality within 6 months after initial discharge. Geriatr Gerontol Int 2021; 21: 926–931. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods: The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results: Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion: The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid. [ABSTRACT FROM AUTHOR]

Purpose: Coronavirus disease 2019 (COVID-19) has placed a great burden on critical care services worldwide. Data regarding critically ill COVID-19 patients and their demand of critical care services outside of initial COVID-19 epicenters are lacking. This study described clinical characteristics and outcomes of critically ill COVID-19 patients and the capacity of a COVID-19-dedicated intensive care unit (ICU) in Kobe, Japan. Methods: This retrospective observational study included critically ill COVID-19 patients admitted to a 14-bed COVID-19-dedicated ICU in Kobe between March 3, 2020 and June 21, 2020. Clinical and daily ICU occupancy data were obtained from electrical medical records. The last follow-up day was June 28, 2020. Results: Of 32 patients included, the median hospital follow-up period was 27 (interquartile range 19–50) days. The median age was 68 (57–76) years; 23 (72%) were men and 25 (78%) had at least one comorbidity. Nineteen (59%) patients received invasive mechanical ventilation for a median duration of 14 (8–27) days. Until all patients were discharged from the ICU on June 5, 2020, the median daily ICU occupancy was 50% (36–71%). As of June 28, 2020, six (19%) died during hospitalization. Of 26 (81%) survivors, 23 (72%) were discharged from the hospital and three (9%) remained in the hospital. Conclusion: During the first months of the outbreak in Kobe, most critically ill patients were men aged ≥ 60 years with at least one comorbidity and on mechanical ventilation; the ICU capacity was not strained, and the case-fatality rate was 19%. [ABSTRACT FROM AUTHOR]

Background: Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.Methods: We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.Results: Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.Conclusions: Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients. [ABSTRACT FROM AUTHOR]

Summary: Immune checkpoint inhibitors can induce immune-related adverse events (irAEs) in different organs. Dermatomyositis is a rare form of systemic irAE. Although dermatomyositis-specific antibodies, especially anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibodies, have been detected in a few cases of immune checkpoint inhibitor-associated dermatomyositis, their titers before immunotherapy have not been examined. We hereby report the first irAE case of dermatomyositis accompanied by seroconversion of anti-TIF1-γ antibody following nivolumab treatment for advanced lung adenocarcinoma. A 64-year-old Japanese male with an advanced lung adenocarcinoma (cT4N2M1a stage IVA) received nivolumab as third-line therapy. Skin rashes appeared two days later, and were treated with a topical steroid as just drug eruptions. 7 weeks later, he was emergently admitted because of high serum creatine kinase level. Clinical examination showed deteriorated rashes along with slightly weakened proximal muscles. Muscle biopsy revealed myopathic changes consistent with dermatomyositis. Anti-TIF1-γ antibody was positive, which was found to be within normal range before nivolumab administration. He was diagnosed with dermatomyositis and treated with systemic corticosteroids, tacrolimus, and intravenous immunoglobulin. However, these drugs showed limited effectiveness against the progression of muscle weakness. He died of respiratory failure due to lung cancer and muscle weakness progression 6 months after the admission. In conclusion, our case demonstrates that the development of dermatomyositis was causally related to immune activation by nivolumab. Given the potential exacerbation of autoimmune paraneoplastic disorders in cancer patients receiving immunotherapy, clinicians should be aware of early manifestations of systemic irAEs that require prompt diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Summary: Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated associations between early depth of response and survival outcomes among patients receiving nivolumab for NSCLC. Methods Using records from prospective observational cohorts, we identified 83 previously treated advanced patients with NSCLC who received nivolumab during 2016–2017. Thirty-one patients who achieved disease control were analyzed. Tumor assessments followed the Response Evaluation Criteria in Solid Tumors (RECIST). Using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses, treatment outcomes were compared with percent tumor reductions from baseline to the first evaluation (8–12 weeks after starting nivolumab). Results Early depth of response was predictive of 6-month progression-free survival (area under the ROC curve, 0.848). Based on ROC results, early tumor shrinkage was defined as a > 10% reduction by the first evaluation. Early tumor shrinkage was associated with significantly longer median progression-free survival (early tumor shrinkage: 16.6 months, 95% confidence interval [CI] 8.5 months–not reached; no early shrinkage: 5.1 months, 95% CI 3.9–6.8 months; P < 0.001) and significantly longer median overall survival (P = 0.046). Conclusions Early depth of tumor shrinkage was associated with outcomes after ICI treatment. Because of its simplicity and predictive ability, early tumor shrinkage may be a promising factor for use in clinical settings. However, confirmation of our results is needed. [ABSTRACT FROM AUTHOR]

Purpose: Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible after CRT in the real world. No study has been conducted on the patients who were ineligible for the PACIFIC trial, and hence, we conducted a retrospective study on them.Methods: We identified 82 patients with stage III NSCLC who received definitive platinum-based concurrent CRT and had World Health Organization performance status of 0-1. We investigated the proportion, clinical characteristics, and prognoses of patients who became ineligible for the PACIFIC trial after CRT.Results: After CRT, 19 of 82 patients (23%) became ineligible for the PACIFIC trial. Comparison between eligible and ineligible patients revealed that old age (p = 0.042), male gender (p = 0.031), and radiation therapy with V20 ≥ 35% (p = 0.032) were associated with ineligibility after CRT. Moreover, ineligible patients showed shorter PFS (6.6 vs. 15.7 months, hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.16-5.89, p = 0.016) and shorter OS (18.6 vs. 44.3 months, HR 3.03, 95% CI 1.29-7.10, p = 0.007) than eligible patients.Conclusions: Our study revealed the clinical characteristics and prognoses of patients who became ineligible for the PACIFIC trial after CRT. Physicians should be careful while prescribing CRT for patients with characteristics such as old age, male gender, and radiation therapy with V20 ≥ 35%. [ABSTRACT FROM AUTHOR]

Osimertinib is a standard second-line therapy for patients who develop EGFR Thr790Met resistance mutation after treatment with first-line epidermal growth factor receptor tyrosine kinase inhibitors. Although no other effective targeted treatment option exists for these patients, osimertinib might be permanently discontinued owing to the onset of severe drug-induced toxicities like hepatotoxicity. Herein, we report a case of successful oral desensitization with osimertinib after the patient developed osimertinib-induced fever and hepatotoxicity. In the present case report, a 62-year-old Japanese woman received osimertinib as the sixth-line therapy for non-small cell lung carcinoma harboring EGFR Thr790Met-mutation. After 15 days of treatment, she developed general malaise. Although we reduced the drug at a lower dose, she again presented with high fever and elevated serum AST/ALT levels three days after re-initiating treatment. We then attempted oral desensitization with osimertinib over a two-week period. Thereafter, the patient continued osimertinib treatment for 6 months without the recurrence of side effects. In conclusion, oral desensitization may be a useful method in treating hepatotoxicity and drug fever caused by osimertinib. [ABSTRACT FROM AUTHOR]

Background: Relatively little is known about acute exacerbation (AE) of interstitial pneumonia associated with collagen vascular diseases (CVD-IPs). Objectives: This study was aimed at clarifying clinical characteristics and outcome in AE of CVD-IPs, compared with those of idiopathic interstitial pneumonias (IIPs). Methods: We retrospectively reviewed 112 admission cases with suspected AE of CVD-IPs or IIPs during 2003-2009. IIPs were diagnosed with idiopathic pulmonary fibrosis (IPF) or non-IPF, mostly based on radiologic findings. Of these, 15 AEs of CVD-IPs (6 rheumatoid arthritis, 6 dermatomyositis and 3 systemic sclerosis) and 47 AEs of IIPs (13 IPF and 34 non-IPF) were included. Results: The clinical characteristics in AE of CVD-IPs were similar to those of IIPs, except for younger age (63.3 ± 6.8 vs. 73.8 ± 9.1 years; p = 0.0001) and higher PaO2/FiO2 at the onset of AE (205 ± 81.2 vs. 145 ± 53.8 mm Hg; p = 0.002) in the former. Dermatomyositis-related interstitial pneumonia (IP) showed a relatively indolent onset and was often associated with worsening control of the underlying disease, whereas AE of other CVD-IPs resembled that of IIPs. 90-day mortality of 33% in AE of CVD-IPs was similar to that of IIPs (44%; p = 0.44) or non-IPF (34%; p = 0.94), but was significantly better than that of IPF (69%; p = 0.04). Conclusion: Clinical features and outcome in AE of CVD-IPs were similar, if not identical, to those of IIPs, having a significant impact on the clinical course. AE of advanced IPF with typical radiologic features seems to have higher mortality compared with other forms of IP. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been shown to improve oxygenation in cases of diffuse alveolar damage, but little is known about its effectiveness in treating pneumocystis pneumonia (PCP) in HIV-negative immunosuppressed patients. Objectives: This study was aimed at investigating the effect of PMX-DHP in treating non-HIV-related PCP. Methods: Between October 2005 and September 2008, 6 patients with non-HIV-related PCP were treated with 2 sessions of PMX-DHP at an attending physician's discretion when severe hypoxemia developed despite conventional treatments including high-dose corticosteroid, whereas 9 patients in a similar condition were treated without PMX-DHP. Changes in oxygenation and radiographic findings in the PMX-DHP group and adverse events associated with PMX-DHP were investigated retrospectively, as were the outcomes for both treatment groups. Results: There was an improvement in PaO2/FiO2 during each PMX-DHP session, from 148.8 ± 52.5 to 188.2 ± 79.3 mm Hg (p = 0.02). After 2 sessions of PMX-DHP, an improvement in PaO2/FiO2, from 131.8 ± 37.4 to 213.3 ± 87.3 mm Hg, was observed (p = 0.04), but no significantly different improvement was detected on the following day. The radiographic findings improved in 4 patients during PMX-DHP. The in-hospital mortality was similarly high in both groups (50% in the PMX-DHP group vs. 67% in the non-PMX-DHP group). No significant adverse events associated with PMX-DHP were observed except for advanced thrombocytopenia in 1 patient. Conclusion: PMX-DHP may serve as an adjunct in the treatment of non-HIV-related PCP, temporarily alleviating severe hypoxemia even in cases refractory to conventional treatments. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions Paraneoplastic neurological syndrome (PNS) is associated with small‐cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real‐world data from patients with PNS complicated by SCLC.Patients diagnosed with Stage II–IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS).A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3–4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23).A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS. [ABSTRACT FROM AUTHOR]

The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy. Methods: One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009. Results: The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval [CI], 5–15%), 44% (95% CI, 35–53%), and 2.0 months (95% CI, 1.4–2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4–16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12–43%); DCR, 72% (95% CI, 53–86%); and median PFS, 3.4 months (95% CI, 2.4–4.9 months). Conclusions: Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies. [Copyright &y& Elsevier]

Background In December 2015, nivolumab was approved for previously treated advanced NSCLC irrespective of PD-L1 expression or histology in Japan. Real-world data can provide insights beyond the clinical trial, and in this analysis we study a large Japanese patient cohort. Methods Data for 901 patients who initiated nivolumab treatment for advanced NSCLC from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan, including clinical laboratory data before and all the available data during nivolumab treatment. Here we report an exploratory analysis on the association of nivolumab effectiveness with the clinical laboratory data of the Japanese advanced NSCLC patients from a multicenter, observational study; CA209-9CR (NCT03273790). Results Analysis on association of objective response rate (ORR) with each clinical laboratory data at baseline among responders and non-responders suggested that neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), albumin, sodium, CYFRA, and uric acid at baseline were associated with significantly improved ORR. Further analyses on those multiple factors are planned to identify associations with improved outcome of with nivolumab treatment beyond ORR. [ABSTRACT FROM AUTHOR]