Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.     

Brainstem ischemia and preeclampsia.

Diffuse neurological manifestations of preeclampsia are due to endothelial involvement that lead to ischemia, hemorrhage, or edema. We analyzed clinical and radiological features and the course of brainstem ischemic strokes in a preeclampsia patient. We report a case of severe preeclampsia in a 30-year-old woman who was admitted 10 hr after a vaginal delivery at home. The pregnancy was at 39 wk, with no prenatal care. At her admission, she was conscious, and she had tetraparesia, swinging deep tendon reflex testing, drowsiness, and dysarthria; the BP was at 160/100 mmHg and 4 + proteinuria; magnetic resonance imaging revealed brainstem ischemic stroke. The evolution was favorable with symptomatic treatment. The patient was discharged on the 16th day; 2 months later she had a normal recovery. Brainstem strokes are rare. They are frequently due to hemorrhage; sometimes, they can also be ischemic. Their course is favorable.     

Isolation and Characterization of Lytic Pseudomonas aeruginosa Bacteriophages Isolated from Sewage Samples from Tunisia

Bacteriophages could be a useful adjunct to antibiotics for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. In this study, lytic P. aeruginosa myoviruses PsCh, PsIn, Ps25, and Ps12on-D were isolated from Tunisian sewage samples. Phage Ps12on-D displayed an adsorption time of ~10 min, a short latency period (~10 min), and a large burst size (~115 PFU per infected cell) under standard growth conditions. All phages were active at broad temperature (4 °C to 50 °C) and pH (3.0 to 11.0) ranges and were able to lyse a wide variety of P. aeruginosa strains isolated from clinical and environmental samples worldwide. Illumina sequencing revealed double-stranded DNA genomes ranging from 87,887 and 92,710 bp with high sequence identity to Pseudomonas phage PAK_P1. All four phages based on sequence analysis were assigned to the Pakpunavirus genus. The presented characterization and preclinical assessment are part of an effort to establish phage therapy treatment as an alternative strategy for the management of multidrug-resistant P. aeruginosa infections in Tunisia.     

Photocatalytic Activity of Silicon Nanowires Decorated with PbS Nanoparticles Deposited by Pulsed Laser Deposition for Efficient Wastewater Treatment

The present work aims to study the photocatalytic properties of nanohybrids composed of silicon nanowires (SiNWs) decorated with PbS nanoparticles (NPs). The elaborated material was intended to be utilized in wastewater treatment. The SiNWs were elaborated from the Metal Assisted Chemical Etching route (MACE), while the PbS NPs were deposited at room temperature onto SiNWs using the pulsed laser deposition (PLD) technique. The influence of decorating SiNWs (having different lengths) with PbS-NPs on their structural, morphological, optoelectronic, and photocatalytic properties was scrutinized. PbS/SiNWs nanohybrids exhibited enhanced photocatalytic degradation towards Black Amido (BA) dye for 20 µm SiNWs length and 0.2% of BA volume concentration. These optimized conditions may insinuate that this nanocomposite-like structure is a promising efficient photocatalytic systems contender, cost-effective, and recyclable for organic compound purification from wastewaters.     

Consequences of non-medical switch among patients with type 2 diabetes

Objective: This study aimed to describe real-world experiences following a non-medical switch among adults with type 2 diabetes mellitus (T2DM) in the United States.

Methods: For this cross-sectional study, patients with T2DM (N?=?451) provided data on demographics, and how a non-medical switch of their anti-hyperglycemic agent (AHA) affected their general health, HbA1c levels and medication management, via an Internet-based survey. Patients self-reported their level of satisfaction with the original medication and emotional reactions to the non-medical switch. Patients who recently experienced a non-medical switch of their AHA(s) (n?=?379) were asked about the consequences of switching and their satisfaction with the switch (vs. the original) medication.

Results: Patients most frequently reported feeling very/extremely frustrated, surprised, upset and angry in reaction to a non-medical switch. Patients were somewhat satisfied with their original medication. Between 20% and 30% of patients reported the non-medical switch had a moderate/major effect on their general health, diabetes, mental well-being and control over their health. The blood glucose levels of recent switchers were somewhat/much worse (20.7%) and medication management was somewhat/much worse (12.9%) on the switch (vs. the original) medication. Some recent switchers reported old symptoms returning (7.7%) and experiencing new side-effects (14.2%).

Conclusions: Approximately one in five patients reported a moderate/major negative impact on their blood glucose level, diabetes, mental well-being, general health and control over their health following a non-medical switch. Findings suggest that a non-medical switch may have unintended negative health consequences and results in considerable burden across multiple domains for a sizeable minority of patients with T2DM.     

Fluid responsiveness predicted by noninvasive Bioreactance-based passive leg raise test

Purpose  

To study the feasibility of predicting fluid responsiveness (FR) by passive leg raising (PLR) using a Bioreactance-based noninvasive cardiac output monitoring device (NICOM).     

Impact of socio-economic status on hospital length of stay following injury: a multicenter cohort study

Background

Injury is second only to cardiovascular disease in terms of acute care costs in North America. One key to improving injury care efficiency is to generate knowledge on the determinants of resource use. Socio-economic status (SES) is a documented risk factor for injury severity and mortality but its impact on length of stay (LOS) for injury admissions is unknown. This study aimed to examine the relationship between SES and LOS following injury.This multicenter retrospective cohort study was based on adults discharged alive from any trauma center (2007–2012; 57 hospitals; 65,486 patients) in a Canadian integrated provincial trauma system. SES was determined using ecological indices of material and social deprivation. Mean differences in LOS adjusted for age, gender, comorbidities, and injury severity were generated using multivariate linear regression.

Results

Mean LOS was 13.5 days. Patients in the highest quintile of material/social deprivation had a mean LOS 0.5 days (95 % CI 0.1-0.9)/1.4 days (1.1-1.8) longer than those in the lowest quintile. Patients in the highest quintiles of both social and material deprivation had a mean LOS 2.6 days (1.8-3.5) longer than those in the lowest quintiles.

Conclusions

Results suggest that patients admitted for traumatic injury who suffer from high social and/or material deprivation have longer acute care LOS in a universal-access health care system. The reasons behind observed differences need to be further explored but may indicate that discharge planning should take patient SES into consideration.

     

Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis.

Normal gestation is associated with a hyperdynamic adaptive state. The circulatory changes represent an additional burden on the cardiovascular system of women with rheumatic mitral stenosis (MS). Life-threatening complications can occur in pregnant women with severe MS. We successfully performed percutaneous balloon mitral valvotomy (PMV) in eight pregnant patients (mean age 28 +/- 6.9 years, range 21-38 years). Pregnancy mean age was 24.6 +/- 6.5 weeks. Five patients were in NYHA functional class III and three patients were in class IV. Emergency PMV seemed to be life saving to both mother and foetus in one case. All patients but one had pliable valves. PMV was achieved using the double balloon transseptal technique. To protect the foetus from radiation, the patient's pelvic-abdominal area was shielded and left ventriculography was not performed. The total mean time of PMV was 72 +/- 19 min and that of fluoroscopy was 16.6 +/- 7.8 min. Gorlin's mitral valve area increased from 0.83 +/- 0.15 to 2.4 +/- 0.34 cm2 and the cardiac index from 3.1 +/- 0.77 to 4.2 +/- 0.79 l.min-1.m-2. Left atrium pressure decreased from 29 +/- 10 to 14 +/- 5 mmHg and mitral valve gradient from 21 +/- 7 to 6 +/- 3 mmHg. There were no complications or residual MS. At a mean follow-up of 13.2 +/- 9.4 months, all patients were in NYHA class I and had a normal course of pregnancy. The eight women delivered healthy full-term babies. At 1-25 months post-partum follow-up, the eight infants had shown normal growth and development.(ABSTRACT TRUNCATED AT 250 WORDS)