Efficacy of tyrosine kinase inhibitors in patients with non-small-cell lung cancer with performance status 4: a case series and review of the literature.

BACKGROUND: Current guidelines for non-small-cell lung cancer (NSCLC) recommend that each tyrosine kinase inhibitor (TKI) is indicated even for driver mutation-positive patients with a poor performance status (PS). In previous studies, most patients had a PS of 2-3, but those with a PS of 4 were very few. Therefore, the efficacy of TKIs in patients with NSCLC with a PS of 4 remains unclear. CASE PRESENTATION: We retrospectively reviewed the clinical records of four patients with NSCLC with PS 4 treated with TKIs: an 89-year-old Japanese woman (Case 1), a 80-year-old Japanese woman (Case 2), an 50-year-old Japanese man (Case 3), and a 81-year-old Japanese woman (Case 4). Genetic alterations were epidermal growth factor receptor (EGFR), MET exon 14 skipping, BRAFV600E, and ROS1 proto-oncogene receptor tyrosine kinase (ROS1). One case with ROS1 fusion showed a significant response with the recovery of PS. However, in the remaining three cases (i.e., EGFR, MET exon 14 skipping, and BRAFV600E mutations), patients died despite the administration of TKIs. These three patients had to be hospitalized at the end of their life to receive treatment. CONCLUSIONS: This is the first case series to summarize the efficacy of TKIs in patients with NSCLC with a PS of 4. Additionally, this case series poses a question concerning the indication of TKIs for older patients with a PS of 4.

Effectiveness of point of care ultrasound (POCUS) simulation course and skills retention for Japanese nurse practitioners.

BACKGROUND: In Japan, the nurse practitioner (NP) system has only been in place for a short time, and there is no ultrasound (US) simulation course for NPs. Therefore, NPs may have to attend US simulation courses for physicians. We evaluated whether US simulation course for physicians lead to improved image acquisition and interpretation amongst NPs and, if so, if these changes would be maintained over time. METHODS: A 2-day point-of-care ultrasound (POCUS) course designed for physicians in cardiac US, lung US, lower extremity deep vein thrombosis (DVT) US, and abdominal US was held for Japanese nurse practitioners (JNP) and JNP trainees in 2018 and 2019. Participants kept a record of the number of US examinations they performed for 3 months before and 3 months after the course. The number of US exams performed was grouped into six categories. All participants underwent pre-course, immediate post-course, and 4-month post-course testing to assess image interpretation skills, image acquisition skills, and confidence. RESULTS: Thirty-three participants from 21 facilities completed the program. Before and immediately after the course, test scores of the image interpretation test, image acquisition test, and confidence increased significantly (37.1, 72.6: P < 0.001), (13.7, 53.6: P < 0.001), and (15.8, 35.7: P < 0.001), respectively. Comparing the follow-up tests immediately after the course and 4 months later, there was no decrease in scores on the image interpretation test, the image acquisition test, or confidence (72.6, 71.8: P = 1.00) (53.6, 52.9: p = 1.00) (35.7, 33.0: P = 0.34). There was a statistically significant increase (P < 0.001) in both the total number of ultrasound examinations and in the number of ultrasound examinations by category (cardiac, lung, lower extremity DVT, and abdominal) in the 3 months before and 3 months after the course. CONCLUSIONS: The POCUS simulation course for physicians is useful for JNPs to acquire US examination skills even if it is not arranged for JNPs. Image interpretation skill, image acquisition skill, and confidence improved significantly and were maintained even after 4 months of the course. It leads to behavioral changes such as increasing the number of US examinations in daily practice after the course.

Dabrafenib plus trametinib treatment for a patient with BRAF V600E-mutated large-cell lung carcinoma and a poor performance status.

Dabrafenib plus trametinib is active against metastatic lung cancer with the BRAF V600E mutation. However, the feasibility of dabrafenib plus trametinib for patients with a poor performance status (PS) has not been reported. We report the case of an 80-year-old woman was diagnosed with metastatic large-cell lung carcinoma. Her general statuses worsened due to cancer, resulting in a PS of 4. Genotype testing revealed a BRAF V600E mutation. The patient received dabrafenib plus trametinib without significant adverse effects. This report is the first to describe dabrafenib plus trametinib administration for large-cell lung carcinoma in a patient with a poor PS.

Impact of antibiotic timing relative to percutaneous aspiration on culture positivity rate and clinical outcomes: A retrospective study of patients with pyogenic liver abscess.

The optimal timing of antibiotic administration relative to liver abscess aspiration is debatable. This retrospective cohort study investigated whether the timing affects the abscess culture positivity rate and clinical outcomes. Twenty-nine patients with 30 percutaneously drained liver abscess cases were analyzed. Antibiotics were administered before aspiration (pre-aspiration antibiotics) in 22 cases and following aspiration (post-aspiration antibiotics) in 8 cases (i.e., 1 patient underwent aspiration twice, both before and following antibiotics). Both groups demonstrated similar patient characteristics, short time to aspiration, and high antibiotic appropriateness. Most patients were immunocompetent and non-septic. Pre-aspiration antibiotics did not reduce the culture yield (95% with pre-aspiration antibiotics vs. 100% with post-aspiration antibiotics; p = 1). Post-aspiration antibiotics were not associated with higher mortality, longer length of hospitalization, or an increased rate of clinical deterioration following aspiration. With appropriate antibiotic and aspiration, antibiotics timing can be either before or after aspiration without compromising the culture positivity rate and clinical outcomes.

Chylous Ascites Due to Hyperthyroidism and Heart Failure.

Chylous ascites (CA) is the accumulation of fluid with a high triglyceride content in the peritoneal cavity. Only two cases in the literature have reported CA with hyperthyroidism. A 28-year-old previously healthy woman presented with gradual-onset abdominal swelling, exertional dyspnea, and diarrhea. Hyperthyroidism and heart failure were diagnosed using laboratory investigation and echocardiography. Ultrasonography revealed a large amount of ascites. The ascitic fluid was milky with elevated triglyceride levels. Treatment with anti-thyroid therapy and diuretics improved all symptoms, and the free triiodothyronine (T3) level normalized after five days. Hyperthyroidism and heart failure should be considered as reversible causes of CA.

Acute Lower Extremity Arterial Thrombosis Associated with Osimertinib-Induced Erythrocytosis.

BACKGROUND Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced non-small cell lung cancer (NSCLC) with positive EGFR mutation. Rashes, nail toxicity, and diarrhea are common adverse events. Hematological adverse effects, including anemia, thrombocytopenia, and lymphocytopenia, have been reported. However, erythrocytosis has not been reported as an adverse event. To the best of our knowledge, we report the first case of acute lower extremity thrombosis presumably caused by osimertinib-induced erythrocytosis. CASE REPORT A 70-year-old man with epidermal EGFR-mutant advanced NSCLC presented with acute left sural pain. The patient's left foot was cold, and peripheral arterial Doppler signals were absent. He had developed erythrocytosis of unknown etiology during osimertinib therapy. Hemoglobin (Hb) and hematocrit were 22.6 g/dL and 62.5%, respectively. Contrast-enhanced computed tomography showed thrombotic occlusion of the popliteal artery. Other than erythrocytosis, there was no possible cause of arterial thrombosis. Osimertinib was discontinued immediately because the NSCLC started to resist treatment and was presumed to be the cause of erythrocytosis. He received endovascular treatment (EVT). Following serial EVT and debridement, his fourth toe was amputated for necrosis. Erythrocytosis persisted 8 months during osimertinib therapy. Hb levels decreased to 15.4 mg/dL due to blood loss complicated with catheter thrombectomy and remained normal for 20 months after osimertinib discontinuation. The patient died of cancer progression. CONCLUSIONS This case suggests the erythrocytosis was possibly caused by osimertinib. We may need to monitor Hb levels during osimertinib therapy and be alert to thrombosis once Hb starts to rise.

The effectiveness of a national early warning score as a triage tool for activating a rapid response system in an outpatient setting: A retrospective cohort study.

Rapid response system (RRS) efficacy and national early warning score (NEWS) performances have largely been reported in inpatient settings, with few such reports undertaken in outpatient settings.This study aimed to investigate NEWS validity in predicting poor clinical outcomes among outpatients who had activated the RRS using single-parameter criteria.A single-center retrospective cohort studyFrom April 1, 2014 to November 30, 2017 in an urban 350-bed referral hospital in JapanWe collected patient characteristics such as activation triggers, interventions, arrival times, dispositions, final diagnoses, and patient outcomes. Poor clinical outcomes were defined as unplanned intensive care unit transfers or deaths within 24 hours. Correlations between the NEWS and clinical outcomes at the time of deterioration and disposition were analyzed.Among 31 outpatients, the NEWS value decreased significantly after a medical emergency team intervention (median, 8 vs 4, P < .001). The difference in the NEWS at the time of deterioration and at disposition was significantly less in patients with poor clinical outcomes (median 3 vs 1.5, P = .03). The area under the curve (AUC) for the NEWS high-risk patient group at the time of deterioration for predicting hospital admission was 0.85 (95% confidence interval [CI], 0.67-1.0), while the AUC for the NEWS high-risk patient group at disposition for predicting poor clinical outcomes was 0.83 (95% CI, 0.62-1.0).The difference between the NEWS at the time of deterioration and at disposition might usefully predict admissions and poor clinical outcomes in RRS outpatient settings.