Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Intrapulmonary metastasis developing eighteen years after complete resection of thymoma

We present a case of intrapulmonary metastasis developing 18 years after complete resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted on chest X-ray in a 76-year-old woman who had undergone complete resection of Masaoka’s stage II thymoma 18 years earlier. Since the nodule grew to 17 mm during a 2-year follow-up, wedge resection was performed. The lesion was histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely late recurrence after complete resection of thymoma is discussed.     

Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.     

Histochemical studies on hyaluronic acid in the developing human retina

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and theStreptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks’ gestation to the neonatal stage.     

Clinical significance of sialic acid in the CSF; in relation to the malignancy and leptomeningeal dissemination

We examined the level of sialic acid in cerebrospinal fluid (CSF) in 20 patients with brain tumor, and 5 patients with non-neoplastic disease of central nervous system. CSF concentration of sialic acid in the patients with malignant and semi-malignant or benign brain tumor was 5.26 +/- 2.39 mg/dl, and 1.82 +/- 1.61 mg/dl, respectively. In patients with non-neoplastic disease, it was 1.64 +/- 1.53 mg/dl. The difference between groups was statistically significant (p less than 0.005). In two patients with malignant brain tumor, the level of sialic acid was decreased by radiation therapy or intrathecal chemotherapy. In conclusion, CSF concentration of sialic acid was significant of diagnosis of brain tumor character of malignancy, and effect of therapy for CSF dissemination.     

Urinary FDP D-dimer and E fragments in renal transplantation

Both D-dimer and E fragments in urinary FDP were determined in renal transplantation patients. Urinary D-dimer fragments increased in 14 out of 20 acute rejections (70.0%) and in 6 out of 18 chronic rejections (33.3%). Urinary E fragments increased in 8 out of 9 acute rejections (88.9%) and in 4 out of 5 chronic rejections (80.0%). It is suggested that urinary FDP-E fragment is a better indicator to detect or predict rejection than the whole Urinary FDP. The appearance of D-dimer in the urine indicates intravascular coagulation in glomeruli followed by a secondary fibrinolysis in the course of the rejection reaction. The urinary D-dimer/FDP ratio which was used as the indicator of fibrinolytic activity in glomeruli was obtained in various conditions of renal transplants. The ratios were relatively high in the urines from well functioning grafts. This ratio deteriorated at the onset of rejection crisis and tended to go upward during the course of the recovery when the rejection was reversible. In the cases of irreversible acute rejection and chronic rejection, these ratios remained at a low level. D-dimer/FDP ratio might be useful indicator to predict the reversibility of rejection and the prognosis of renal allograft. Furthermore, these findings suggest that fibrinolytic and thrombolytic therapy by the tissue-type plasminogen activator (t-PA) along with immunosuppressive drugs might be more effective for the treatment of these rejections.