Assessing EGFR-mutated NSCLC with bone metastasis: Clinical features and optimal treatment strategy.

BACKGROUND: This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) mutation and to identify the most effective treatment strategy using EGFR-tyrosine kinase inhibitors (TKIs). METHODS: The study included patients with stage IV EGFR-mutated NSCLC who were receiving first-line treatment with EGFR-TKIs between January 2014 and December 2020. These patients were divided into two groups based on the presence or absence of BoM at the time of initial diagnosis. The BoM group was further subdivided based on whether they received denosumab or not. RESULTS: The final analysis included 247 patients. Those with BoM at initial diagnosis had shorter progression-free survival (12.6 vs. 10.5 months, p = 0.002) and overall survival (OS) (49.7 vs. 30.9 months, p = 0.002) compared to those without BoM. There was a difference in the location of metastatic sites between the two groups, with a higher incidence of extrathoracic metastasis in the BoM group (p < 0.001). The incidence of T790M was higher in patients with BoM than in those without (47.4% vs. 33.9%, p = 0.042). Multivariate Cox regression analysis revealed that sequential osimertinib treatment and the addition of antiangiogenic therapy (AAT) and denosumab therapy improved OS in patients with BoM. CONCLUSIONS: The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes.

Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units.

BACKGROUND: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.

Clinical characteristics and treatment outcomes among the hospitalized elderly patients with COVID-19 during the late pandemic phase in central Taiwan.

BACKGROUND: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents. METHODS: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality. RESULTS: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups. CONCLUSIONS: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality.

Effect of pre-hospitalization use of oral antiviral agents on reducing critical illness and mortality for patients with COVID-19 pneumonia.

OBJECTIVES: This study aimed to evaluate the effect of administering nirmatrelvir/ritonavir and molnupiravir before hospitalisation on subsequent critical illness among patients with COVID-19 pneumonia. METHODS: This retrospective cohort study included patients with COVID-19 pneumonia who required hospitalisation between 1 January 1 2022 and 31 August 2022. The primary outcomes were the development of critical illness, including intensive care unit admission, use of mechanical ventilation, or mortality. A multivariate logistic regression analysis was conducted to assess the varying risks of critical illness and mortality. A total of 1,011 COVID-19 patients were analysed. Among them, 304 (30.1%) received molnupiravir and 131 (13.0%) received nirmatrelvir/ritonavir before hospitalisation. RESULTS: There were significant reductions for critical illness (adjusted odds ratio 0.29, 95% confidence interval 0.21-0.39, P < 0.001) and mortality (adjusted odds ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001) in patients receiving oral antivirals compared with those who did not. No significant differences in critical illness were observed between molnupiravir and nirmatrelvir/ritonavir. The combination of COVID-19 vaccines and oral antivirals can further reduce the risk of critical illness in high-risk populations. CONCLUSION: Administering molnupiravir and nirmatrelvir/ritonavir before hospitalisation reduced the risk of COVID-19 patients with moderate to severe pneumonia progressing to critical illness and mortality.

High mortality of patients with severe pneumonia caused by respiratory syncytial virus, August 2021-June 2023, Taiwan.

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care-associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co-infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %.

A real-world study comparing perioperative chemotherapy and EGFR-tyrosine kinase inhibitors for treatment of resected stage III EGFR-mutant adenocarcinoma.

BACKGROUND: The patient population with stage III non-small-cell lung cancer (NSCLC) is heterogeneous, with varying staging characteristics and diverse treatment options. Despite the potential practice-changing implications of randomized controlled trials evaluating the efficacy of perioperative epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), concerns have been raised due to conflicting overall survival (OS) results. Few real-world studies have examined the survival outcomes of patients with resected EGFR-mutant stage III adenocarcinoma receiving perioperative chemotherapy and EGFR-TKIs. METHODS: In this retrospective observational study, we enrolled patients with resected stage III adenocarcinoma with EGFR mutations between January 2011 and December 2021. Patients were classified into two groups: perioperative chemotherapy and perioperative EGFR-TKIs. Outcomes and prognostic factors were analyzed using Cox proportional hazards regression analysis. RESULTS: Eighty-four patients were enrolled in the analysis. Perioperative EGFR-TKIs led to longer progression-free survival (PFS) than chemotherapy (38.6 versus 14.2 months; p = 0.019). However, only pathological risk factors predicted poor PFS in multivariate analysis. Patients receiving perioperative chemotherapy had longer OS than those receiving EGFR-TKIs (111.3 versus 50.2 months; p = 0.052). Multivariate analysis identified perioperative treatment with EGFR-TKIs as an independent predictor of poor OS (HR: 3.76; 95% CI: 1.22-11.54). CONCLUSION: Our study demonstrates that chemotherapy should be considered in the perioperative setting for high-risk patients, when taking pathological risk factors into consideration, and that optimized sequencing of EGFR-TKIs might be the most critical determinant of OS.

Outcomes and Prognostic Factors in Critical Patients with Hematologic Malignancies.

Patients with hematologic malignancies (HMs) have a significantly elevated risk of mortality compared to other cancer patients treated in the intensive care unit (ICU). The prognostic impact of numerous poor outcome indicators has changed, and research has yielded conflicting results. This study aims to determine the ICU and hospital outcomes and risk factors that predict the prognosis of critically ill patients with HMs. In this retrospective study, conducted at a referral hospital in Taiwan, 213 adult patients with HMs who were admitted to the medical ICU were evaluated. We collected clinical data upon hospital and ICU admission. Using a multivariate regression analysis, the predictors of ICU and hospital mortality were assessed. Then, a scoring system (Hospital outcome of critically ill patients with Hematological Malignancies (HHM)) was built to predict hospital outcomes. Most HMs (76.1%) were classified as high grade, and more than one-third of patients experienced a relapsed or refractory disease. The ICU and hospital mortality rates were 55.9% and 71.8%, respectively. Moreover, the disease severity was high (median Sequential Organ Failure Assessment (SOFA) score: 11 and Acute Physiology and Chronic Health Evaluation (APACHE II) score: 28). The multivariate analysis revealed that high-grade HMs, invasive mechanical ventilation requirement, renal replacement therapy initiation in the ICU, and a high SOFA score correlated with ICU mortality. Furthermore, a higher HHM score predicted hospital mortality. This study demonstrates that ICU mortality primarily correlates with the severity of organ dysfunction, whereas the disease status markedly influences hospital outcomes. Furthermore, the HHM score significantly predicts hospital mortality.

Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study.

The combination of bevacizumab or ramucirumab with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, or immunotherapy for non-small-cell lung cancer (NSCLC) patients with EGFR mutations could have survival benefits. However, no study, to date, has been conducted to compare the efficacy and safety of these two antiangiogenic therapies (AATs). Stage IIIB to IV EGFR-mutated NSCLC patients who received first-line EGFR-TKIs between January 2014 and May 2022 were enrolled. These patients were divided into two groups: those receiving bevacizumab and those receiving ramucirumab as a combination therapy in any line of treatment. Ninety-six patients were enrolled in this study's final analysis. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261). Patients who received these two different AATs did not differ in PFS (24.1 vs. 15.7 months, p = 0.454) and OS (48.6 vs. 43.0 months, p = 0.924). In addition, these two AATs showed similar frequencies of the T790M mutation (43.6% vs. 38.2%; p = 0.645). Multivariate Cox regression analysis indicated several AAT cycles as an independent good prognostic factor in OS. The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. Front-line AAT and EGFR-TKI combination therapy improved the PFS of stage IV EGFR-mutated NSCLC patients. The effectiveness and safety of the two AATs were similar.

Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma.

Pulmonary Aspergillus infection may have a variety of manifestations depending on the patients' immunity status and pre-existing lung conditions. Radiographically, aspergilloma, which is usually associated with noninvasive Aspergillus fumigatus conidia, may feature a characteristic mass in a cavity commonly located in the upper lobes of the lung. It is typically encountered upon pre-existing lung damage. Here we report Aspergillus growing in a pulmonary metastatic cavity in a 47-year-old male worker with a history of tongue cancer after a radical operation with neck dissection and concurrent chemotherapy in 2014. Chest radiography and computed tomography showed a cavitary lesion with a ball-in-hole lesion in the right upper lobe (RUL) and two cystic lesions within the bilateral upper lung field. Endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) from the RUL anterior segmental bronchus (RB3) revealed the presence of Aspergillus conidia and squamous cell carcinoma. Wedge resection of the cystic lesion within the left upper lobe confirmed the diagnosis of metastatic squamous cell carcinoma. This is a rare case of aspergillosis within cavities of pulmonary metastases in a patient who was diagnosed with tongue squamous cell carcinoma. The conclusive distinction between neoplasm and fungal infection is difficult to achieve by radiography, and a pathological biopsy by EBUS-TBB is necessary to aid diagnosis. Clinicians should be aware of such an atypical presentation of metastases coexisting with Aspergillus infection.

Using real-time visualization system for data-driven decision support to achieve lung protective strategy: a retrospective observational study.

BACKGROUND: Although lung protective strategy and adjunctive intervention are associated with improved survival in patients with acute respiratory distress syndrome (ARDS), the implementation of effective therapies remains low. This study aimed to evaluate whether the use of business intelligence (BI) for real-time data visualization is associated with an improvement in lung protective strategy and adjunctive therapy. METHODS: A retrospective observational cohort study was conducted on patients with ARDS admitted between September 2020 and June 2021 at two intensive care units (ICUs) of a tertiary referral hospital in Taiwan. BI was imported for data visualization and integration to assist in clinical decision in one of the ICUs. The primary outcomes were the implementation of low tidal volume ventilation (defined as tidal volume/predicted body weight ≤ 8 mL/kg) within 24 h from ARDS onset. The secondary outcomes included ICU and hospital mortality rates. RESULTS: Among the 1201 patients admitted to the ICUs during the study period, 148 (12.3%) fulfilled the ARDS criteria, with 86 patients in the BI-assisted group and 62 patients in the standard-of-care (SOC) group. Disease severity was similar between the two groups. The application of low tidal volume ventilation strategy was significantly improved in the BI-assisted group compared with that in the SOC group (79.1% vs. 61.3%, p = 0.018). Despite their ARDS and disease severity, the BI-assisted group tended to achieve low tidal volume ventilation. The ICU and hospital mortality were lower in the BI-assisted group. CONCLUSIONS: The use of real-time visualization system for data-driven decision support was associated with significantly improved compliance to low tidal volume ventilation strategy, which enhanced the outcomes of patients with ARDS in the ICU.

When to add anti-angiogenesis drugs to EGFR-mutated metastatic non-small cell lung cancer patients: a real-world study from Taiwan.

BACKGROUND: The addition of anti-angiogenesis drugs to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) or chemotherapy in patients with EGFR-mutant non-small cell lung cancer (NSCLC) can improve disease control. We conducted a study to evaluate the efficacy of combination therapeutic strategies and identify patients who could benefit from combination therapy. METHODS: This study enrolled patients with stage IV EGFR-mutant NSCLC treated with first-line EGFR-TKIs between January 2014 and December 2020. We divided patients into three groups: patients who received an anti-angiogenesis drug as first-line combination therapy, those who received an anti-angiogenesis drug as further-line combination therapy, and those with no anti-angiogenesis therapy. RESULTS: A total of 204 patients were enrolled in the final analysis. Progression-free survival (PFS) in patients receiving first-line anti-angiogenesis plus EGFR-TKI combination therapy was longer (18.2 months) than those treated with first-line EGFR-TKI monotherapy (10.0 months for both, p < 0.001). No difference in overall survival (OS) was observed among these three groups (30.5 vs. 42.6 vs. 33.7 months, p = 0.326). Multivariate Cox regression analysis revealed L858R mutation, pleural, liver, and bone metastasis as independent prognostic factors for poor OS. However, the addition of anti-angiogenesis therapy to patients with these poor prognostic factors improved OS to levels similar to those without these poor prognostic factors. CONCLUSION: First-line combination EGFR-TKI plus anti-angiogenesis therapy improves PFS in patients with stage IV EGFR-mutant NSCLC. Adding an anti-angiogenesis drug at any line to patients harboring L858R mutation with pleural, liver, or bone metastases can provide survival benefits.

Bevacizumab plus dacomitinib combination therapy for L858R-mutated metastatic lung adenocarcinoma: A report of two cases.

Dual inhibition of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor pathways for the treatment for EGFR-mutated, metastatic non-small cell lung cancer is supported by previous randomized controlled trials. However, the use of second-generation irreversible EGFR tyrosine kinase inhibitor (TKI) dacomitinib in combination with antiangiogenic therapy has not been reported in the literature. Here, we report the case of a 73-year-old man who presented with hemoptysis and dyspnea on exertion and was diagnosed with right upper lung adenocarcinoma with pleural metastasis and L858R mutation. The second case is of a 60-year-old woman who presented with low back pain and was diagnosed with right lower lung adenocarcinoma with bone metastasis and L858R mutation. Both patients underwent first-line therapy with the TKI dacomitinib in combination with bevacizumab. The first patient showed a nearly complete response, and the second patient showed a partial response after the combination therapy and no severe side effects.

The Feasibility of Interventional Pulmonology Methods for Detecting the T790M Mutation after the First or Second-Generation EGFR-TKI Resistance of Non-Small Cell Lung Cancer.

The development of third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeting T790M-mutant non-small cell lung cancer (NSCLC) has raised the importance of re-biopsy after EGFR-TKI failure. This study aimed to investigate the feasibility of interventional pulmonology (IP) procedures as re-biopsy methods for identifying the T790M mutation in EGFR-TKI-resistant patients. One hundred and thirty-nine NSCLC patients who underwent IP procedures for re-biopsy as their initial investigation after EGFR-TKI treatment failure were enrolled in this study between January 2020 and August 2022. All patients underwent a first re-biopsy with IP methods, with a diagnostic yield of 81.2% and T790M mutation detection rate of 36%. Thirty patients underwent a second re-biopsy; IP methods were used for 17 (56.6%) patients and non-IP methods for 13 (43.4%) patients; the T790M mutation detection rate was 36.4%. Only six patients underwent a third re-biopsy; no T790M mutation was noted. The T790M mutation detection rate did not differ between IP and non-IP methods (33.6 % vs. 37.5%, p = 0.762). In 11 cases (7.5%), a re-biopsy revealed histologic transformation from lung adenocarcinoma. IP procedures, as first-line re-biopsy methods for NSCLC, are feasible and provide sufficient tissue for identification of the resistance mechanism and target gene T790M mutation.

Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials.

Prevention of cardiorenal syndrome through treatment with inotropic agents remains challenging. This network meta-analysis evaluated the safety and renoprotective effects of inotropes on patients with advanced heart failure (HF) using a frequentist random-effects model. A systematic database search was performed until 31 January 2021, and a total of 37 trials were included. Inconsistency, publication bias, and subgroup analyses were conducted. The levosimendan group exhibited significantly decreased mortality compared with the control (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.46-0.84), milrinone (OR: 0.50; 95% CI: 0.30-0.84), and dobutamine (OR: 0.75; 95% CI: 0.57-0.97) groups. In terms of renal protection, levosimendan (standardized mean difference (SMD): 1.67; 95% CI: 1.17-2.18) and dobutamine (SMD: 1.49; 95% CI: 0.87-2.12) more favorably improved the glomerular filtration rate (GFR) than the control treatment did, but they did not significantly reduce the incidence of acute kidney injury. Furthermore, levosimendan had the highest P-score, indicating that it most effectively reduced mortality and improved renal function (e.g., GFR and serum creatinine level), even in patients with renal insufficiency. In conclusion, levosimendan is a safe alternative for protecting renal function on cardiorenal syndrome in patients with advanced HF.

Comprehensive Comparisons among Inotropic Agents on Mortality and Risk of Renal Dysfunction in Patients Who Underwent Cardiac Surgery: A Network Meta-Analysis of Randomized Controlled Trials.

Several kinds of inotropes have been used in critically ill patients to improve hemodynamics and renal dysfunction after cardiac surgery; however, the treatment strategies for reducing mortality and increasing renal protection in patients who underwent cardiac surgery remain controversial. Therefore, we performed a comprehensive network meta-analysis to overcome the lack of head-to-head comparisons. A systematic database was searched up to 31 December 2020, for randomized controlled trials that compared different inotropes on mortality outcomes and renal protective effects after cardiac surgery. A total of 29 trials were included and a frequentist network meta-analysis was performed. Inconsistency analyses, publication bias, and subgroup analyses were also conducted. Compared with placebo, use of levosimendan significantly decreased the risks of mortality (odds ratio (OR): 0.74; 95% confidence interval (CI): 0.56-0.97) and risk of acute renal injury (OR: 0.61; 95% CI: 0.45-0.82), especially in low systolic function patients. Use of levosimendan also ranked the best treatment based on the P-score (90.1%), followed by placebo (64.5%), milrinone (49.6%), dopamine (49.5%), dobutamine (29.1%), and fenoldopam (17.0%). Taking all the available data into consideration, levosimendan was a safe renal-protective choice for the treatment of patients undergoing cardiac surgery, especially for those with low systolic function.

Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature.

Pleural effusions are rarely observed in association with acute myeloid leukemia (AML), and their true incidence remains unknown. Given the low diagnostic yield from cytopathologic analysis of malignant pleural effusions and the fact that patients with leukemia are often thrombocytopenic and unable to tolerate invasive procedures, the incidence of leukemic effusions may be underestimated. Here, we report a rare case of pleural effusion in a patient with newly diagnosed AML. Initial analysis revealed an exudative, lymphocyte-predominant effusion. High levels of adenosine deaminase (ADA) were detected in pleural fluid, consistent with a diagnosis of tuberculosis. However, the analysis of pleural cytology revealed leukemic cells, permitting the diagnosis of leukemic effusion to be made. The patient underwent induction chemotherapy and pleural effusion resolved without recurrence. This case emphasizes the diagnostic dilemma presented by high levels of ADA in a leukemic pleural effusion, as this association has not been previously considered in the literature.

Endobronchial metastases from a primary embryonal carcinoma.

We report the case of a 24-year-old man who presented with chief complaints of shortness of breath and haemoptysis; chest radiography revealed complete collapse of the left lung. Bronchoscopy revealed an endobronchial tumour with complete obstruction of the left main bronchus. Cryosurgical excision was performed; tissue pathology confirmed the diagnosis of metastatic embryonal carcinoma. The patient underwent a right orchiectomy followed by a bleomycin + etoposide + cisplatin (BEP) chemotherapy regimen.