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.

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.

High Stroke Volume Variation Is an Independent Predictor for Decreased Blood Pressure During Hemodialysis.

It currently remains unclear whether stroke volume variation (SVV) before hemodialysis (HD) is an independent predictor of decreased blood pressure (BP) during HD. Fifty-two patients were divided into two groups (Decreased BP during HD group: N = 10, Non-decreased BP group: N = 42). Fractional shortening was lower, and mean arterial pressure (MAP) and SVV were higher in the Decreased BP during HD group. A multiple logistic regression analysis identified low fractional shortening, high MAP, and high SVV as independent predictors of decreased BP during HD. The areas under the ROC curves were as follows: 0.849 for MAP, 0.712 for SVV, and 0.893 for MAP and SVV. Optimal threshold values were 93.0 mm Hg for MAP and 17.3 % for SVV. A multivariate regression analysis identified anemia and a longer dialysis vintage as independently related factors for higher SVV. Our results suggest that high SVV is an independent predictor for decreased BP during HD.

Effective uric acid-lowering treatment for hypertensive patients with hyperuricemia.

Uric acid (UA) has been associated with hypertension, renal disease and cardiovascular disease. The aim of the present study was to compare the UA-lowering effects of a standard dose of the UA synthesis inhibitor febuxostat to a standard dose of the uricosuric agent benzbromarone, and to investigate the effects of a low-dose combination of both agents in hypertensive patients with hyperuricemia. Twenty hypertensive patients with inadequate UA control were administered febuxostat 40 mg (Feb), benzbromarone 50 mg (Ben) and febuxostat 20 mg and benzbromarone 25 mg (feb/ben) for 3 months each in a randomized modified crossover manner. UA metabolism, blood pressure (BP) and the indices of organ damage were assessed at baseline and the end of each treatment period. No significant changes were observed in BP or estimated glomerular filtration rate (eGFR) after the treatment with each UA-lowering regimen. The change in UA was significantly greater with feb/ben than with Feb. The excretion of UA and clearance of UA were higher with Ben than with Feb and feb/ben. Urinary 8-hydroxydeoxyguanosine and liver-type fatty-acid-binding protein levels were slightly lower with Ben, whereas flow-mediated dilation was slightly higher with feb/ben and Ben. The UA-lowering effects of the low-dose combination of the UA synthesis inhibitor and uricosuric agent were greater than those of the standard dose of each agent alone. The uricosuric agent may be more effective at improving vascular function than the UA synthesis inhibitor. Thus, the appropriate management of hyperuricemia with uricosuric drugs appears to be useful for hypertensive patients with hyperuricemia.

Trends in the awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic: A one-year follow-up study.

The aim of the present study was to investigate trends in the awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic following guidance regarding salt restriction. Subjects comprised 107 patients (mean age 71 ± 12 years) who were followed at a hypertension clinic and 164 patients (mean age 68 ± 11 years) who were followed at a general clinic. Estimated salt intake using spot urine samples and awareness of salt intake using a self-description questionnaire were assessed in 2013 and one year after guidance regarding salt restriction. No significant changes were observed in office blood pressure at the two clinics. Estimated salt intake in 2013 was slightly lower at the hypertension clinic than at the general clinic (8.9 ± 2.5 vs 9.3 ± 2.5 g/day). Estimated salt intake decreased and the awareness of salt intake improved significantly after one year at both clinics; however, the reduction in estimated salt intake was larger at the general clinic than that at the hypertension clinic (-1.6 ± 3.2 vs -0.6 ± 2.9 g/day, p < 0.01). Individual guidance including data on actual salt intake appeared to be effective and important for reducing salt intake in hypertensive patients.

Effects of a selective aldosterone blocker and thiazide-type diuretic on blood pressure and organ damage in hypertensive patients.

The aim of the present study was to compare the effects of the aldosterone blocker eplerenone and thiazide-like diuretic indapamide on blood pressure (BP) and target organs with reference to salt intake in hypertensive outpatients. Twenty hypertensive patients (nine women and 11 men, mean age 71 ± 13 years) with inadequate BP control despite taking calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were administered eplerenone (50 mg/day) or indapamide (1 mg/day) for 3 months each in a randomized crossover manner. Salt intake, BP and indices of organ damage were assessed at baseline and at the end of each treatment period. Eplerenone and indapamide were similarly effective in lowering office and home BPs. Both the treatments significantly reduced the estimated glomerular filtration rate (eGFR) and increased serum uric acid levels. The treatment with eplerenone significantly increased serum potassium levels, whereas the treatment with indapamide significantly decreased them. The treatment with eplerenone significantly decreased pulse wave velocity and urinary 8-hydroxydeoxyguanosine levels. These changes were not significantly affected by the treatment with indapamide. In conclusion, eplerenone and indapamide were similarly effective in lowering office and home BPs in hypertensive patients treated with CCBs and ARBs. Eplerenone may exert more favorable effects on arterial stiffness and oxidative stress.

Related factors for worsening renal function following percutaneous transluminal renal angioplasty (PTRA) in patients with atherosclerotic renal artery stenosis.

PURPOSE: To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA. METHODS: We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA. RESULTS: A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055). CONCLUSIONS: Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic.

The purpose of the present study was to investigate awareness of salt restriction and actual salt intake in hypertensive patients at a hypertension clinic and general clinic. Subjects included 330 patients, with a mean age of 69±12 years, who were followed at a hypertension clinic and 200 patients, with a mean age of 67±11 years, who were followed at a general clinic. We estimated 24-h salt excretion using spot urine samples and checked the awareness of salt intake using a self-description questionnaire. The number of antihypertensive drugs available at the hypertension clinic was significantly higher than that at the general clinic (2.2±1.1 versus 1.6±0.9, p<0.01); however, no significant difference was observed in office systolic blood pressure between the two groups. Urinary salt excretion was significantly lower at the hypertension clinic than at the general clinic (8.7±2.5 versus 9.3±2.5 g/d, p<0.01). The rate of achievement of salt intake<6 g/d was 15% at the hypertension clinic and 6% at the general clinic. In patients with excessive salt intake (≥10 g/d), 28% of patients at the hypertensive clinic and 23% at the general clinic thought that their salt intake was low. Urinary salt excretion in hypertensive patients was lower at a hypertensive clinic than at a general clinic. This may be due to the professional nutritional guidance at the hypertension clinic. However, most patients could not comply with the guidelines, and the awareness of salt restriction in patients with excessive salt intake was low.