Nanoparticle albumin bound-paclitaxel for treatment of advanced non-small cell lung cancer: an evaluation of the clinical evidence

Introduction: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a microtubule inhibitor, has demonstrated clinical efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) either as monotherapy or in combination. Nab-paclitaxel was developed to reduce the toxicities associated with solvent-bound paclitaxel (sb-paclitaxel).

Areas covered: This review first focuses on the clinical trials evaluating the efficacy and tolerability of nab-paclitaxel in NSCLC at different settings. The approval of nab-paclitaxel in combination with carboplatin at the front-line setting for advanced NSCLC was based on the key phase III study, which showed that nab-paclitaxel/carboplatin was associated with superior overall response rate and favorable toxicity profile compared to sb-paclitaxel/carboplatin. The review also addresses the nab-paclitaxel pharmacology, other combinations (e.g. immunotherapy with PD-1/PD-L1 inhibitors), potential biomarkers (e.g. caveolin-1), and special subgroups (e.g. the elderly, squamous histology).

Expert opinion: Existing data has established the role of nab-paclitaxel in the management of advanced NSCLC. Emerging evidence, such as preliminary results from Keynote-407 and IMpower 131 studies, indicates that novel combinations of nab-paclitaxel/carboplatin and PD-1/PD-L1 inhibitors could further improve clinical benefits with manageable toxicity. Nevertheless, in order to better position nab-paclitaxel and to improve patient selection, future studies are warranted to further understand its mechanism of action, predictive biomarkers, and potential synergism with other agents.     

Intraoperative Patterns of Gastric Microperfusion During Laparoscopic Roux-en-Y Gastric Bypass

Introduction

Visible light spectroscopy (VLS) represents a sensitive, non-invasive method to quantify tissue oxygen levels and detect hypoxemia. The aim of this study was to assess the microperfusion patterns of the gastric pouch during laparoscopic Roux-en-Y gastric bypass (LRYGB) using the VLS technique.

Methods

Twenty patients were enrolled. Tissue oxygenation (StO2%) measurements were performed at three different localizations of the gastric wall, prior and after the creation of the gastric pouch, and after the creation of the gastro-jejunostomy.

Results

Prior to the creation of the gastric pouch, the lowest StO2% levels were observed at the level of the distal esophagus with a median StO2% of 43 (IQR 40.8–49.5). After the creation of the gastric pouch and after the creation of the gastro-jejunostomy, the lowest StO2% levels were recorded at the level of the His angle with median values of 29% (IQR 20–38.5) and 34.5% (IQR 19–39), respectively. The highest mean StO2 reduction was recorded at the level of the His angle after the creation of the gastric pouch, and it was 18.3% (SD ± 18.1%, p < 0.001). A reduction of StO2% was recorded at all localizations after the formation of the gastro-jejunostomy compared to the beginning of the operation, but the mean differences of the StO2% levels were statistically significant only at the resection line of the pouch and at the His angle (p = 0.044 and p < 0.001, respectively).

Conclusion

Gastric pouch demonstrates reduction of StO2% during LRYGB. VLS is a useful technique to assess microperfusion patterns of the stomach during LRYGB.

Graphical abstract

     

Die Postarthroskopische Osteonekrose

Osteonecrosis after arthroscopic meniscectomy is a rare postoperative complication. The precise etiology as well as the specific pathomechanism are unknown. There are only case reports in the literature about postarthroscopic osteonecrosis; large series with long-term follow-up are missing. Differential diagnosis between postarthroscopic osteonecrosis and primary osteonecrosis already present before arthroscopy but undiagnosed is only possible by stage-dependent imaging. This study evaluates the current status of knowledge about postarthroscopic osteonecrosis.     

Skin problems after a tsunami

BACKGROUND: On December 26, 2004, the biggest earthquake for 40 years, measuring 9.0 on the Richter scale, triggered a tsunami that pounded the coastal areas of South Asia and East Africa. The effects of the tsunami on skin conditions have not been evaluated. OBJECTIVE: To determine the influence of the tsunami on skin conditions by evaluating the skin problems of patients presenting at hospitals after the tsunami. METHODS: Between 5 and 25 January 2005, two dermatologists evaluated patients who complained of skin problems at an outpatient clinic and emergency room of a general hospital in Banda Aceh, Aceh Province, Indonesia. RESULTS: The total number of patients that presented during the study period was 235 (131 males and 104 females), and they had a total of 265 skin problems. In terms of age distribution, most subjects were in their fourth decade (23.0%), followed by the third (22.6%) and fifth decade (16.6%). The most prevalent skin problems were infections-infestations (32.5%), followed by eczemas (29.8%) and traumatic skin disorders (29.4%). In males, traumatic skin disorders were most common. The great majority of infection-infestation cases involved superficial fungal infections. Contact dermatitis accounted for three-quarters of eczema cases, and mainly involved the arms (40.0%) and legs (27.1%). The majority of traumatic skin disorders were lacerations, punctures and penetrations, and the feet (44.7%) and hands (18.8%) were most frequently affected. CONCLUSIONS: Unhygienic conditions, exposure to a hazardous environment and contact with various objects during and after the tsunami probably increased the prevalence of infections-infestations, traumatic skin disorders and contact dermatitis. To prevent these problems and associated secondary bacterial infections, health-related education and early medical management are required.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Alpha 2-antiplasmin, plasminogen activator inhibitor (PAI) and dilute blood clot lysis time in selected disease states.

This paper is an attempt to assess the relevance of the inhibitors of fibrinolysis for clot lysis in selected disease states and to discuss the mechanisms leading to acquired abnormal levels of such inhibitors. When compared to 20 control subjects the 30 hypertriglyceridemic patients (14 with type IIb and 16 with type IV) displayed significantly (p less than 0.001) increased plasma plasminogen activator inhibitor (PAI) activity (221 +/- 88% and 290 +/- 104% respectively; mean +/- SD), moderately (p less than 0.01) increased alpha 2 antiplasmin (alpha 2AP) level (112 +/- 11% and 115 +/- 16%) and accordingly an obviously prolonged dilute blood clot lysis time (DBCLT). Neither PAI activity and alpha 2AP level nor DBCLT were significantly different from controls in the 10 patients with hyperlipoproteinemia type IIa. The 18 patients with severe hepatic cirrhosis had low alpha 2AP level (59 +/- 19.7%) and accelerated clot lysis, while mean PAI activity (160 +/- 87%) was slightly (p less than 0.05) increased. In the 17 nephrotic patients alpha 2AP was increased (115 +/- 12%) while PAI activity was similar to controls and DBCLT rather shorter. Two liver secretion enzymes, namely serum cholinesterase and plasma protein C, were found to be decreased in cirrhotic patients, similar to control values in hyperlipoproteinemia type IIa and obviously increased in nephrotic patients as well as in hypertriglyceridemic subjects. The relevance of PAI and alpha 2AP for clot lysis was considered in relation to data in the literature concerning the behaviour of t-PA and factor XIII.(ABSTRACT TRUNCATED AT 250 WORDS)     

Innovative solutions: Standardized concentrations facilitate the use of continuous infusions for pediatric intensive care unit nurses at a community hospital.

The pediatric intensive care unit at a community hospital successfully implemented the use of standardized concentrations. The process included deciding the standardized concentrations, use of titration charts, and integration of smart pump technology. Since the implementation of standardized concentrations, there has been no signal or sentinel events reported. It is safe and efficacious to use standardized concentrations combined with smart pump technology and abandon the use of the rule of 6 in the pediatric population.