Prognostic Value of the Geriatric Nutritional Risk Index in Previously Untreated Patients With Advanced NSCLC Treated With a Combination Therapy of Anti-PD-1/-PD-L1 Antibodies and Platinum-Based Chemotherapy: A Multicenter Retrospective Study.

INTRODUCTION: Combination therapy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies and platinum-based chemotherapy has been widely used as a first-line treatment for patients with unresectable advanced non-small cell lung cancer (NSCLC) in clinical settings; however, prognostic biomarkers associated with survival outcomes have not been sufficiently investigated. METHODS: We enrolled 147 previously untreated patients with advanced NSCLC who were treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy at eight institutions in Nagano Prefecture between December 2018 and April 2023. We evaluated the prognostic value of the geriatric nutritional risk index (GNRI), a systemic inflammatory nutritional biomarker calculated from body weight and serum albumin level, for patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy. RESULTS: The cutoff value of the GNRI was set at 92. The high GNRI and low GNRI groups included 88 and 59 patients, respectively. The median follow-up period was 15.9 months. The overall survival (OS) in the high GNRI group was significantly longer than that in the low GNRI group (27.9 vs. 15.6 months, p = 0.015). Multivariate analysis revealed that a high GNRI was an independently favorable prognostic predictor for OS (hazard ratio, 1.73; 95% confidence interval, 1.06-2.86; p = 0.031). CONCLUSION: The present study demonstrates that the GNRI is a useful prognostic predictor in patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy in clinical settings.

Predictive Factors Associated with Long-Term Response to Combination Immunotherapy in Patients with Untreated Advanced Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

INTRODUCTION: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. METHODS: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. RESULTS: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. CONCLUSION: The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy.

Bronchoscopy-Guided Cooled Radiofrequency Ablation as a Novel Intervention Therapy for Peripheral Lung Cancer.

BACKGROUND: Our previous animal and preliminary human studies indicated that bronchoscopy-guided cooled radiofrequency ablation (RFA) for the lung is a safe and feasible procedure without major complications. OBJECTIVES: The present study was performed to evaluate the safety, effectiveness and feasibility of computed tomography (CT)-guided bronchoscopy cooled RFA in patients with medically inoperable non-small-cell lung cancer (NSCLC). METHODS: Patients with pathologically diagnosed NSCLC, who had no lymph node involvement or distant metastases (T1-2aN0M0) but were not surgical candidates because of comorbidities (e.g., synchronous multiple nodules, advanced age, cardiovascular disease, poor pulmonary function, etc.) were enrolled in the present study. The diagnosis and location between the nearest bronchus and target tumor were made by CT-guided bronchoscopy before the treatment. A total of 28 bronchoscopy-guided cooled RFA procedures were performed in 20 patients. After treatment, serial CT imaging was performed as follow-up. RESULTS: Eleven lesions showed significant reductions in tumor size and 8 lesions showed stability, resulting in a local control rate of 82.6%. The median progression-free survival was 35 months (95% confidence interval: 22-45 months), and the 5-year overall survival was 61.5% (95% confidence interval: 36-87%). Three patients developed an acute ablation-related reaction (fever, chest pain) and required hospitalization but improved with conservative treatment. There were no other adverse events in the present study. CONCLUSIONS: CT-guided bronchoscopy cooled RFA is applicable for only highly selected subjects; however, our trial may be an alternative strategy, especially for disease local control in medically inoperable patients with stage I NSCLC.

Urinary tract infection associated with bacteremia caused by vancomycin-resistant enterococcus following continent urinary diversion.

Key Clinical Message: Even in a country where vancomycin-resistant enterococcus is rare, multidrug-resistant organism precautions are necessary when admitting patients with a history of medical exposure in other countries. On admission, screening is necessary and if infection is confirmed, a multidisciplinary approach involving different specialists is required. Abstract: The patient was a 49-year-old Japanese female living in the United States. Total pelvic exenteration for cervical carcinoma, Miami pouch formation, and ileostomy had been performed in the United States. She returned to Japan to undergo postoperative adjuvant chemotherapy. Fever and abdominal pain occurred 42 days after surgery. She consulted the fever outpatient clinic, and a diagnosis of urinary retention-associated acute renal failure and pyelonephritis was made. We detected vancomycin-resistant enterococcus on urine/blood culture 5 days after admission. Infection control measures were implemented, and the ward was closed for 3 days. We administered linezolid, which was effective for pyelonephritis and bacteremia.

EGFR-TKI rechallenge in patients with EGFR-mutated non-small-cell lung cancer who progressed after first-line osimertinib treatment: A multicenter retrospective observational study.

BACKGROUND: Rechallenge therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is known to confer some clinical benefit for patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). However, little is known about the efficacy of EGFR-TKI rechallenge after resistance to first-line (1L) osimertinib. This study aimed to assess the efficacy and safety of EGFR-TKI rechallenge therapy after resistance to 1L osimertinib in a Japanese clinical setting. METHODS: Between April 2018 and August 2022, 26 patients who progressed after treatment with 1L osimertinib and received EGFR-TKI rechallenge were included in this multicenter retrospective analysis. Patients in whom 1L osimertinib was discontinued owing to toxicity and had subsequent disease progression were also included in the analysis. RESULTS: Overall, the objective response rate for rechallenge therapy was 23.1%. The disease control rate was 53.9%, and the median progression-free survival (PFS) was 3.4 months. Patients who discontinued 1L osimertinib for toxicity had a higher response rate (42.9% vs. 15.8%) and longer PFS than those who discontinued it due to disease progression (median: 11.4 vs. 2.7 months, P = 0.001). Three patients (11.5%) developed rechallenge therapy-associated pneumonitis, two of which were grade ≥3. CONCLUSIONS: Rechallenge with EGFR-TKI after 1L osimertinib resistance showed limited clinical efficacy. However, it could be considered as a subsequent salvage therapeutic option for patients in whom 1L osimertinib was discontinued owing to toxicity.

Impact of pneumothorax-like pulmonary collapse caused by rapid bronchial obstruction: A case report of pneumothorax ex vacuo.

We report two cases of pulmonary collapse that simulated pneumothorax on computed tomographic images and were caused by rapid complete bronchial obstruction. One patient was a 77-year-old woman with sudden dyspnea, and the other was an 83-year-old woman with sudden dyspnea who was infected with influenza A virus. Chest computed tomography revealed lobular complete atelectasis with an almost complete expansion of the other lobes of the right lung. Some air space in the right pleural cavity was also observed. Both cases were diagnosed as "pneumothorax" by primary doctors. We noted the disappearance of air density in the lumen of the right bronchus in both cases. We performed bronchoscopy before thoracic drainage and removed the obstruction. Immediately, the obstructed pulmonary lobes expanded, and the air space in the pleural cavity disappeared without thoracic drainage. In the literature, this pneumothorax-like pulmonary collapse is called as "pneumothorax ex vacuo."

C-PLAN index as a prognostic factor for patients with previously untreated advanced non-small cell lung cancer who received combination immunotherapy: A multicenter retrospective study.

BACKGROUND: Combination immunotherapy (immune checkpoint inhibitors and cytotoxic anticancer agents) is widely used as first-line treatment for advanced non-small cell lung cancer (NSCLC). However, the therapeutic effect of combination immunotherapy has not been fully investigated. C-reactive protein, performance status, lactate dehydrogenase, albumin, and derived neutrophil-to-lymphocyte ratio (C-PLAN) are useful biomarkers for predicting the prognosis of NSCLC; however, there are no reports examining the C-PLAN index, which combines these five factors in a single prognostic factor. METHODS: We retrospectively collected data from 178 patients with previously untreated advanced NSCLC who received combination immunotherapy at multicenter institutions in Nagano Prefecture between December 2018 and April 2022. We investigated the utility of the C-PLAN index as a prognostic factor using Cox regression analysis and correlated it with survival. RESULTS: The good and poor C-PLAN index groups included 85 and 93 patients, respectively. The good C-PLAN index group had a longer median progression-free survival (PFS) (10.7 vs. 6.0 months; p = 0.022) and overall survival (OS) (25.3 vs. 16.5 months; p = 0.003) than the poor C-PLAN index group. The C-PLAN index was an independent favorable prognostic factor that correlated with PFS and OS in multivariate analysis. The good C-PLAN index group had a higher proportion of never-smokers (16.5 vs. 4.3%; p = 0.007) and stage III disease/postoperative recurrence (32.9 vs. 15.1%; p = 0.005) than the poor C-PLAN index group. CONCLUSION: The C-PLAN index is a useful prognostic factor for patients with previously untreated advanced NSCLC undergoing combination immunotherapy.

Rechallenge of afatinib for EGFR-mutated non-small cell lung cancer previously treated with osimertinib: a multicenter phase II trial protocol (REAL study).

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR-mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR-dependent resistance after osimertinib treatment, although these have not been prospectively investigated. Methods: The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged ≥20 years) with advanced or recurrent non-squamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023. Discussion: The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established. Registration: UMIN Clinical Trial Registry: UMIN000049225.

Association of Systemic Adverse Reactions and Serum SARS-CoV-2 Spike Protein Antibody Levels after Administration of BNT162b2 mRNA COVID-19 Vaccine.

Objectives The influential factors for anti-severe acute respiratory syndrome coronavirus 2 spike protein antibody (S-ab) levels were assessed after the administration of BNT162b2 mRNA coronavirus disease-2019 (COVID-19) vaccine at short and medium terms. Methods A total of 470 healthcare workers (118 males, mean age 41.0±11.9 years) underwent serum S-ab level measurement at 3 and 8 months after two inoculations of BNT162b2 vaccine given 3 weeks apart, who had no history of COVID-19 were enrolled in this study. The changes and differences after vaccination due to gender and adverse reactions of S-ab were analyzed. Results Systemic adverse reactions incidence (48%) was significantly higher after the second dose than after the first dose (8%). S-ab levels decreased as the age increased (from the 20s to 60s) in both measurements. S-ab level 8 months after the second inoculation [median 476.3 (interquartile range (IQR) 322.4-750.6) U/mL] was significantly lower than that after 3 months [977.5 (637.2-1,409.0) U/mL; p<0.001]. The median decrease rate of S-ab levels in 5 months was 50.3% (IQR 40.3-62.6) and those differences were not observed among all generations. Gender-associated differences in S-ab levels were not observed; however, a significant relationship between higher S-ab levels and the systemic adverse reactions was observed at both measurements. Conclusions The systemic adverse reaction is an independent factor for higher S-ab levels at short and medium terms after BNT162b2 vaccination as demonstrated in our data.

Predictive value of post-treatment C-reactive protein-to-albumin ratio in locally advanced non-small cell lung cancer patients receiving durvalumab after chemoradiotherapy.

BACKGROUNDS: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation-related parameters in patients with LA-NSCLC treated with CCRT plus durvalumab. METHODS: We recruited 76 LA-NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre-treatment) and 2 months after (post-treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression-free survival (PFS) after durvalumab therapy. RESULTS: The median follow-up time was 17 (range, 3.3-35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non-infectious pneumonitis being the most common reason. Post-treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not-reached vs. 9.6 months. Log-rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post-treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). CONCLUSIONS: This study suggests that post-treatment CAR has predictive value for LA-NSCLC patients treated with CCRT plus durvalumab consolidation therapy.

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data.

Introduction: Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017. Methods: This multicenter observational study was conducted by the Japanese Lung Cancer Society using PMACS data with the newly created central registration system regarding patients with NSCLC who received pembrolizumab monotherapy between February 1, 2017 and June 30, 2017; a new database was created by adding the clinical information regarding prognosis for 3 years after therapy to the existing data collected by PMACS. Results: A total of 300 patients from 43 facilities were enrolled in this study. The median overall survival and progression-free survival after pembrolizumab initiation were 558 and 188 days, respectively. Moreover, the 1- and 3-year survival rates were 58.9% and 33.7%, respectively. Results of multivariate analysis revealed performance status (p < 0.0001), histology (p = 0.0118), previous chemotherapy (p = 0.0007), programmed death-ligand 1 expression status (p = 0.0195), and previous steroid use (p = 0.0460) as significant factors that affected overall survival. The toxicity profile was similar to that previously reported. Conclusions: In this first attempt to use PMACS data, we successfully collected clinical information and found the real-world efficacy and safety of pembrolizumab.

Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed.

The role of second-line and salvage chemotherapy in malignant pleural mesothelioma treatment is not yet established. We report a case of relapsed malignant pleural mesothelioma in which the patient failed to respond to pemetrexed-based chemotherapy but was successfully treated with gemcitabine and vinorelbine. The patient underwent a left extrapleural pneumonectomy. Three years later she developed anterior chest wall and retroperitoneal masses. Histological findings revealed metastases from the malignant pleural mesothelioma. Although two cycles of carboplatin plus pemetrexed chemotherapy were administered, she had progressive disease. Then, 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine were administered every 2 weeks. The chemotherapy regimen was tolerated well, and the tumors were remarkably reduced. She was treated with 12 cycles of gemcitabine plus vinorelbine, and 8.5 months of progression-free survival was observed. Gemcitabine plus vinorelbine chemotherapy may be a candidate regimen for salvage chemotherapy against malignant pleural mesotheliomas.

A case of severe ARDS caused by novel swine-origin influenza (A/H1N1pdm) virus: a successful treatment with direct hemoperfusion with polymyxin B-immobilized fiber.

In 2009, a 35-year-old female with Down syndrome was admitted to our hospital because of severe pneumonia caused by an infection with the novel swine-origin influenza (A/H1N1pdm) virus (S-OIV). A chest X-ray on admission revealed bilateral infiltration shadows. Although mechanical ventilation was administered because of the development of ARDS, the hypoxemia continued to progressed. We observed evidence of alveolar hemorrhage on evaluation of the patient using bronchofiberscopy. The bacterial examination was negative. Despite intensive care, including respiratory management with high-frequency oscillatory ventilation (HFOV), the patient's hypoxemia and hypotension progressed. We concluded that a cytokine storm due to the influenza infection with SIRS caused shock status, resulting in septic shock. We subsequently treated the patient with direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP). The hypoxemia improved immediately. She was free from mechanical ventilation and discharged from the hospital by the 17th day of her hospitalization. PMX-DHP seems to improve hypoxemia in patients with severe ARDS who cannot maintain sufficient respiratory control under mechanical ventilation. This case is the first report about severe and life-threatening ARDS due to the novel influenza, in which PMX-DHP showed beneficial effects.

[A case of a pulmonary pleomorphic carcinoma with fever which responded well to chemotherapy].

BACKGROUND: Pulmonary pleomorphic carcinoma is a very rare pulmonary malignant tumor which has various clinical manifestations and a poor prognosis. CASE: A 74-year-old man presented with fever and weight loss of more than 10kg during 2 months from April 200X. Chest CT showed a nodule in the right upper lobe, and supraclavicular and mediastinal lymphadenopathy. Positron emission tomography (PET) comfirmed 18Ffluorodeoxyglucose accumulation in the sites. A left supraclavicular node biopsy demonstrated pulmonary pleomorphic carcinoma. The tumors responded well to gemcitabine plus docetaxel combination chemotherapy. This symptoms disappeared and the response continued for 1 year after 6 cycles of chemotherapy. CONCLUSION: We report a case of pulmonary pleomorphic carcinoma presenting with fever, which showed a marked response to chemotherapy.

A novel device (SD-101) with high accuracy for screening sleep apnoea-hypopnoea syndrome.

BACKGROUND AND OBJECTIVE: The SD-101 is a non-restrictive, sheet-like medical device with an array of pressure sensors, to detect sleep-disordered breathing by sensing gravitational alterations in the body corresponding to respiratory movements. This study evaluated the accuracy of the SD-101 for screening sleep apnoea-hypopnoea syndrome (SAHS) by comparison with polysomnography. METHODS: Nocturnal polysomnography and SD-101 monitoring were conducted simultaneously and compared in 201 patients with suspected SAHS (suspected SAHS group) and 165 male employees of a transport company (screening group). RESULTS: Polysomnography revealed an AHI of <5, 5 < or = AHI < 15, 15 < or = AHI < 30, 30 < or = AHI < 60 and AHI > or = 60 events/h in 39, 35, 38, 68 and 21 subjects in the suspected SAHS group and 103, 34, 12, 12 and four subjects in the screening group, respectively. Central SAHS and obstructive SAHS were subsequently diagnosed in 11 (5.5%) and 135 (67.2%) of subjects in the suspected SAHS group and five (3.0%) and 39 (23.6%) of subjects in the screening group, respectively. Significant correlations were apparent between AHI and the respiratory disturbance index (RDI) measured with the SD-101 in both the suspected SAHS group (r = 0.88) and screening group (r = 0.92). Receiver operating characteristic curve analysis revealed 89.5% sensitivity and 85.8% specificity in identifying SAHS, using an RDI of 14.0 events/h. CONCLUSIONS: These findings suggest that the SD-101 is a useful device for screening SAHS.

[A squamous cell lung cancer patient who developed immune hemolytic anemia after gemcitabine and docetaxel administration].

A 76-year-old man with squamous cell lung cancer underwent right lower lobectomy in November, 2005. He was diagnosed with pT2N0M0, stage I B, and tegafur/uracil (UFT) was administered. On July, 2007, right hilar lymphadenopathy was detected and considered to be a recurrence. UFT was discontinued, and gemcitabine (GEM) and docetaxel (DOC) combination chemotherapy was initiated on August 21. He began to complain of fatigue, palpitation and dizziness since the fifth day of the administration, and anemia (hemoglobin: Hb 8.7 g/dL) was detected on the fifteenth day. On the twenty-second day of the administration, he was admitted to our hospital because of aggravation of anemia (Hb 6.5 g/dL). His anemia was diagnosed as immune hemolytic anemia based on the laboratory findings including a positive Coombs' test. He showed improvement with prednisolone therapy. The anemia was considered to be drug-induced. This case was extremely rare, and there are no reports on immune hemolytic anemia related to GEM and/or DOC.

[A case of etanercept-induced pneumonitis].

A 64-year-old man was admitted to our hospital because of fever and dyspnea with marked hypoxemia and diffuse ground-glass opacities in bilateral lung fields revealed by a chest CT scan. He had used etanercept therapy for his rheumatoid arthritis. His PaO2/FiO2 had decreased to 130.4 Torr. On bronchoalveolar lavage, lymphocytes were elevated to 54.4% and bacteria culture was negative. We diagnosed drug-induced pneumonitis caused by etanercept, clinically and started high dose corticosteroid therapy. Despite his severe hypoxemia, the corticosteroid therapy and use of non-invasive positive pressure ventilation improved his condition. Interstitial lung disease induced by etanercept is rare, and a severe case requiring mechanical ventilation has never been reported. Because of the critical condition it can cause, it is suggested that evaluation of interstitial pneumonia is crucial.

Clinical analysis of EGFR-positive non-small cell lung cancer patients treated with first-line afatinib: A Nagano Lung Cancer Research Group.

BACKGROUND: In the LUX-Lung 3 and LUX-Lung 6 trials, afatinib improved overall survival in previously untreated patients with EGFR 19del mutated non-small cell lung cancer (NSCLC) compared to chemotherapy. The appropriate management of adverse events and dose reduction of afatinib are important for EGFR-positive NSCLC patients. We conducted a retrospective and observational study of patients treated with first-line afatinib for EGFR-positive NSCLC in Nagano prefecture, Japan, focusing on efficacy and toxicities. METHODS: We retrospectively collected the medical records of NSCLC patients initially treated with afatinib between May 2014 and March 2018. RESULTS: A total of 62 patients with a median age of 67 years and a median body surface area (BSA) of 1.57 m2 were included. The overall response rate was 87.7% and median progression-free survival (PFS) was 15.7 months. The median PFS was similar between standard initial dose (40 mg) and reduced initial doses (30 and 20 mg) (15.7 vs. 14.2 months; P = 0.978). The frequency of dose reduction and the discontinuation rate in the 40 mg daily dose group was higher in patients with BSA < 1.58 m2 (100%) compared to BSA ≥ 1.58 m2 (68.2%) (P = 0.014). The frequency of diarrhea was higher in patients with BSA < 1.58 m2 (93.5%) compared to BSA ≥ 1.58 m2 (71.0%) (P = 0.02). CONCLUSION: In real-world clinical practice, first-line afatinib was well managed and was equally as effective as in previous clinical trials of EGFR-positive NSCLC. BSA is considered a predictive marker for appropriate afatinib dose reduction.

Salmonella houtenae-induced Empyema Complicated with Chronic Tuberculous Empyema.

Salmonella spp. are food-borne pathogens that usually cause gastroenteritis, although bacteremia and subsequent focal metastatic infection can also occasionally occur. Of the known Salmonella spp., Salmonella houtenae is a rare subspecies, comprising less than 1% of all Salmonella strains. We herein report the first case of S. houtenae-induced empyema complicated with chronic tuberculous empyema, which was successfully treated by antibacterial agents alone. We wish to highlight the importance of being aware that Salmonella spp. can cause empyema in cases suffering from chronic tuberculous empyema; moreover, despite the successful completion of treatment with antibacterial agents, periodical follow-up is mandatory in such cases.

Early diagnosis of idiopathic pulmonary haemosiderosis: increased haemosiderin-laden macrophages in repeat bronchoscopy.

Idiopathic pulmonary haemosiderosis (IPH) is a diagnosis of exclusion, which is characterized by persistent or recurrent episodes of alveolar haemorrhage. Early diagnosis of IPH, especially in the case of first-time manifestation, is challenging because previous episodes of alveolar haemorrhage are often difficult to prove. Repeated episodes of alveolar haemorrhage can result in chronic iron-deficient anaemia and irreversible interstitial fibrosis; thus, early recognition and intervention are desirable in terms of clinical outcome. We report a case of IPH that was diagnosed early by confirming the presence of an increased number of haemosiderin-laden macrophages with alveolar haemorrhage in repeat bronchoscopy. We wanted to highlight that decreased but sustained attenuation of ground-glass opacities on high-resolution computed tomography does not always correlate with successful remission in patients with IPH. Repeat bronchoscopy can be useful in the early recognition of IPH, especially in the case of sustained opacities a few months after alveolar haemorrhage.