Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.     

Minimizing the risk of community spread of COVID-19 via institutional quarantine of high-risk travelers with serial viral RNA testing: A successful experience from Macao SAR,China

Macao, a special administrative region (SAR) of the People’s Republic of China, is located in southern China and shares the border with mainland China. It is the most densely populated region in the world, with a population of 667400 and a total land area of 32.9 square kilometers in 2019. Since the first case diagnosed on January 22, 2020, there was a total of 45 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases in Macao, of which 43 patients (96%) were imported cases. To date, all patients had been discharged successfully from Centro Hospitalar Conde de São Januário, a designated hospital to manage all COVID-19 patients in Macao. Eventually, no patient died, and no local community outbreak was noted. This opinion review describes the underlying factors that could have contributed to the successful experience in Macao SAR, China, which include the following: (1) Early implementation of containment measures; (2) Large-scale quarantine using hotel rooms to reduce the risk of a local outbreak; and (3) Multidisciplinary co-operation and transparency of information to the public. Although the successful experience in Macao SAR, China, may not be generalized to other regions, it should not be unreasonable to be well prepared with sufficient logistic support to conduct timely containment and early detection of episodic cases to prevent the backsliding of COVID-19 outbreak.     

Role of Radiation Therapy in Gastric Cancer

Annals of Surgical Oncology - The only curative treatment for localised gastric cancer is surgical resection. However, survival outcomes post-surgery alone remain poor, particularly in those with...     

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

The development of regenerative therapies for cartilage injury has been greatly aided by recent advances in stem cell biology. Induced pluripotent stem cells (iPSCs) have the potential to provide an abundant cell source for tissue engineering, as well as generating patient-matched in vitro models to study genetic and environmental factors in cartilage repair and osteoarthritis. However, both cell therapy and modeling approaches require a purified and uniformly differentiated cell population to predictably recapitulate the physiological characteristics of cartilage. Here, iPSCs derived from adult mouse fibroblasts were chondrogenically differentiated and purified by type II collagen (Col2)-driven green fluorescent protein (GFP) expression. Col2 and aggrecan gene expression levels were significantly up-regulated in GFP+ cells compared with GFP− cells and decreased with monolayer expansion. An in vitro cartilage defect model was used to demonstrate integrative repair by GFP+ cells seeded in agarose, supporting their potential use in cartilage therapies. In chondrogenic pellet culture, cells synthesized cartilage-specific matrix as indicated by high levels of glycosaminoglycans and type II collagen and low levels of type I and type X collagen. The feasibility of cell expansion after initial differentiation was illustrated by homogenous matrix deposition in pellets from twice-passaged GFP+ cells. Finally, atomic force microscopy analysis showed increased microscale elastic moduli associated with collagen alignment at the periphery of pellets, mimicking zonal variation in native cartilage. This study demonstrates the potential use of iPSCs for cartilage defect repair and for creating tissue models of cartilage that can be matched to specific genetic backgrounds.     

Permanent-temporary pacemakers in the management of patients with conduction abnormalities after transcatheter aortic valve replacement

Background

Damage to the cardiac conduction system requiring permanent pacemaker (PPM) implantation is a known adverse outcome of transcatheter aortic valve replacement (TAVR). A permanent-temporary pacemaker (PTPM) is a device that involves an active-fixation lead attached to an external pulse generator taped to the skin. We reviewed the utility of PTPMs as a temporary bridge measure after TAVR in patients with conduction abnormalities that do not meet conventional criteria for PPM placement.

Methods

Between January 01, 2013 and December 31, 2015, we analyzed 67 patients who received PTPM after TAVR. Baseline demographics, comorbidities, type and size of the valve, pre-TAVR electrocardiograms (ECGs), post-TAVR ECGs at 1 day, 1 month, and 6 months, and pacemaker interrogation results were reviewed for each patient if available.

Results

The mean age of patients was 80.5?±?9.1 years. PTPM were placed for 2.3?±?2.4 days. Among these patients, 44.8% (n?=?30) received a PPM prior to discharge. Male gender (OR 2.84, 95% CI 1.05–7.69, p?=?0.05) and an increase in QRS duration post-TAVR (p?=?0.01) were associated with PPM placement. Pacemaker interrogation data of 11 patients with PPM revealed that 27% (n?=?3) had <?1% V-pacing requirements and <?10% A-pacing requirements.

Conclusions

In post-TAVR patients who develop conduction abnormalities that do not meet conventional PPM implantation indications, PTPM safely provides a time period for further assessment and may prevent unnecessary PPM implantation. Male gender and an increase in QRS duration post-TAVR are associated with PPM implantation. Additionally, some patients may recover from their conduction disturbances and demonstrate low pacemaker utilization.

     

Neutrophil activation and production of reactive oxygen species in pre-eclampsia

OBJECTIVE: To investigate neutrophil NADPH oxidase activation and subsequent production of reactive oxygen species (ROS) in pre-eclampsia. DESIGN: Baseline values and the activated response of neutrophils upon stimulation of the NADPH oxidase with the agonists was measured. Neutrophils from 17 third-trimester pre-eclamptic and 17 age- and gestation-matched normal pregnant women were examined. METHODS: Neutrophil ROS production was measured by both lucigenin- and luminol-derived chemiluminescence. The abundance of the various phox proteins was examined using Western blotting techniques. Lucigenin-derived ROS generation was significantly increased in neutrophils isolated from women with pre-eclampsia compared with normotensive controls in the case of both agonists [n-formyl-met-leu-phe (fMLP): pre-eclamptic 2.071 +/- 0.336 relative light units seconds (RLU.s) and normotensive 1.141 +/- 0.249 RLU.s, P = 0.035; phorbol-12-myristate-13-acetate (PMA): pre-eclamptic 34.954 +/- 2.634 RLU.s and normotensive 17.208 +/- 3.325 RLU.s, P = 0.0001]. Luminol-derived ROS generation was also significantly increased in the neutrophils isolated from the women with pre-eclampsia compared with the normotensive controls in the case of both agonists (fMLP: pre-eclamptic 1.955 +/- 0.316 RLU.s and normotensive 1.058 +/- 0.191 RLU.s, P = 0.023; PMA: pre-eclamptic 4.108 +/- 0.351 RLU.s and normotensive 3.073 +/- 0.332 RLU.s, P = 0.042). There were no differences between the relative abundance of the phox proteins in the two groups. CONCLUSIONS: Neutrophils isolated from women with pre-eclampsia during the third trimester showed increased sensitivity to agonist stimulation and produced significantly more ROS than age-matched normotensive controls. This was not due to an increased abundance of any of the phox proteins. Increased ROS production in pre-eclampsia may highlight a role for neutrophils in the oxidative stress and associated endothelial dysfunction that are characteristic of the condition.