Survival Impact of an Enhanced Multidisciplinary Thoracic Oncology Conference in a Regional Community Health Care System.

INTRODUCTION: We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system. METHODS: We implemented a rigorously benchmarked "enhanced" Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011-2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location. We categorized National Comprehensive Cancer Network guideline-concordant treatment as "preferred," or "appropriate" (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-square tests and survival using Cox regression, adjusted for multiple testing. We also performed propensity-matched and adjusted survival analyses. RESULTS: Of 6259 patients, 14% were in eMTOC, 55% metropolitan non-MTOC, and 31% regional non-MTOC cohorts. eMTOC had the highest rates of African Americans (34% versus 28% versus 22%), stages I to IIIB (63 versus 40 versus 50), urban residents (81 versus 78 versus 20), stage-preferred treatment (66 versus 57 versus 48), guideline-concordant treatment (78 versus 70 versus 63), and lowest percentage of nontreatment (6 versus 21 versus 28); all p values were less than 0.001. Compared with eMTOC, hazard for death was higher in metropolitan (1.5, 95% confidence interval: 1.4-1.7) and regional (1.7, 1.5-1.9) non-MTOC; hazards were higher in regional non-MTOC versus metropolitan (1.1, 1.0-1.2); all p values were less than 0.05 after adjustment. Results were generally similar after propensity analysis with and without adjusting for guideline-concordant treatment. CONCLUSIONS: Multidisciplinary NSCLC care planning was associated with significantly higher rates of guideline-concordant care and survival, providing evidence for rigorous implementation of this model of care.

Does systemic administration of casein phosphopeptides affect orthodontic movement and root resorption in rats?

OBJECTIVES: To assess the potential effects of casein phosphopeptides (CPPs) on orthodontically induced iatrogenic root resorption (OIIRR) and orthodontic teeth movement. MATERIALS AND METHODS: Forty Wistar rats (aged 11 weeks) were randomly divided into experimental group (EG; n = 20) that received a diet supplemented with CPP and control group (CG; n = 20) devoid of diet supplement. A 150 g force was applied using nickel titanium (NiTi) coil that was bonded on maxillary incisors and extended unilaterally to a maxillary first molar. At Day 28, animals in both groups were euthanized. Volumetric assessment of root resorption craters and linear measurement of maxillary first molars movement were blindly examined using a micro-computed tomography scan. RESULTS: Nine rats were excluded from the experiment due to loss during general anesthesia or appliances' failure. Intra-operator reproducibility was high in both volumetric and linear measurements, 92.8 per cent and 98.5-97.6 per cent, respectively. The results reveal that dietary CPP has statistically insignificant effect on the overall OIIRR and orthodontic movement. CONCLUSIONS: CPP seems to have statistically insignificant effect on the volume of OIIRR and orthodontic movement in rats. A long-term study with larger sample size using a different concentration of CPP is required to clarify the dentoalveolar effect of CPP.

Combination Ti/PEEK ALIF cage for anterior lumbar interbody fusion: Early clinical and radiological results.

Anterior lumbar interbody fusion (ALIF) is a common procedure for patients with degenerative pathologies of the lumbar spine. In this study, the clinical and radiological outcomes of a combination titanium/polyetheretherketone (Ti/PEEK) ALIF cages in one, two and three-level surgery were evaluated. Over an 18-month time period, a prospective single surgeon series of 20 implants (15 patients) were included in the study, with minimum 10-months follow-up. From these 15 patients, two were supplemented with posterior percutaneous pedicle screw fixation for additional stability. Radiological follow-up with fine cut CT scan at 9-12months was performed to evaluate early fusion rates, and integration of the Titanium/PEEK cage at the endplate junction. 20 implants were followed for a minimum of 10months, and a mean of 15months. A 95% (19/20 implants) fusion rate with no implant related complications was achieved at the mean 15-month postoperative mark. Patients experienced statistically significant improvement in pain and functional outcomes (SF12 and ODI) compared to their pre-operative status. A single patient with a non-union at L5/S1 (smoker) did not experience any improvement in symptoms. A Ti-PEEK cage, with allograft and BMP-2 to achieve interbody fusion is an effective implant for use in anterior lumbar surgery with high fusion rates, no lucency around the titanium endplates at follow-up, and with promising early results.

Molecular targeted therapies for cancer: sorafenib mono-therapy and its combination with other therapies (review).

Sorafenib is an oral multikinase inhibitor that acts by inhibiting tumor growth and disrupting tumor microvasculature through antiproliferative, anti-angiogenic and proapoptotic effects. It exerts these effects via inhibition of multiple targets including Raf serine/threonine kinases, vascular endothelial growth factor receptor tyrosine kinases; VEGFR-1, VEGFR-2, VEGFR-3 and platelet-derived growth factor receptor ß (PDGFR-ß). Current literature shows that the deregulated signaling through these receptors is commonly seen in human tumors. In addition, sorafenib is also shown to induce apoptosis through downregulation of Mcl-1 in many cancer types. Hence, sorafenib as a single agent has shown promising activity in some cancers such as renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and thyroid cancers. Currently, the drug holds FDA approval for the treatment of advanced RCC and unresectable HCC. However, many clinical studies have indicated several limitations to the application of sorafenib as a single agent in various other cancers. Owing to these reasons and the potential of sorafenib to synergize with other anticancer therapies, its combination with other targeted agents and chemotherapy has been widely explored with promising results. In addition, it has also shown synergistic results when combined with radiation. This review summarizes the current basic and clinical studies on the effects and mechanisms of sorafenib either administered alone or in combination with other anticancer treatments.

Wound infusion with local anaesthesia after laparotomy: a randomized controlled trial.

BACKGROUND: The use of a continuous local anaesthesia infusion after laparotomy may reduce opioid requirements and facilitate earlier return of bowel function, independent mobilization and hospital discharge. METHODS: We performed a double-blinded, randomized controlled trial on 55 patients who underwent laparotomy. Patients were randomly allocated to receive a continuous infusion of either 0.2% ropivacaine or normal saline into their midline abdominal wound at the fascial level. The end points of the study were: total opioid requirements at 24 and 48 h; time to first flatus, bowel movement and independent ambulation; length of hospital stay; complications; and daily mean patient-reported pain scores at rest and movement. RESULTS: The two treatment groups were well controlled for factors that influence analgesia requirements, including age, weight, length of wound incision and type of operation. Patients allocated to ropivacaine infusion used, on average, 32 mg less morphine at 48 h (95% confidence interval 7, 57; P= 0.01). This was highly statistically significant after adjusting for age, gender and type of operation (P= 0.0006). Ropivacaine infusion was associated with a significantly decreased time to independent mobilization (P= 0.02), time to first flatus (P= 0.02) and reduced post-operative ileus (2/28 versus 9/27, χ(2) = 5.89, P= 0.02). There was no significant effect of ropivacaine infusion on time to first bowel movement (P= 0.94) nor length of hospital stay (P= 0.77). CONCLUSIONS: Local anaesthesia infusion at the fascial plane provides effective analgesia. This improves patient recovery through earlier return to bowel function and mobilization.

Discerning the Mauve factor, Part 2.

"Mauve Factor" was once mistaken for kryptopyrrole but is the hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-2-one (HPL). Treatment with nutrients--particularly vitamin B6 and zinc--reduces urinary excretion of HPL and improves diverse neurobehavioral symptoms in subjects with elevated urinary HPL. Heightened HPL excretion classically associates with emotional stress, which in turn is known to associate with oxidative stress. For this review, markers for nutritional status and for oxidative stress were examined in relationship to urinary HPL. In cohorts with mixed diagnoses, 24-hour urinary HPL correlated negatively with vitamin B6 activity and zinc concentration in red cells (P < .0001). Above-normal HPL excretion corresponded to subnormal vitamin B6 activity and subnormal zinc with remarkable consistency. HPL correlated inversely with plasma GSH and red-cell catalase, and correlated directly with plasma nitric oxide (P < .0001). Thus, besides implying proportionate needs for vitamin B6 and zinc, HPL is a promising biomarker for oxidative stress. HPL is known to cause non-erythroid heme depression, which lowers zinc, increases nitric oxide, and increases oxidative stress. Administration of prednisone reportedly provoked HPL excretion in animals. Since adrenocorticoid (and catecholamine) stress hormones mediate intestinal permeability, urinary HPL was examined in relationship to urinary indicans, presumptive marker for intestinal permeability. Urinary HPL associated with higher levels ofindicans (P < .0001). Antibiotics reportedly reduce HPL in urine, suggesting an enterobic role in production. Potentially, gut is reservoir for HPL or its precursor, and stress-related changes in intestinal permeability mediate systemic and urinary concentrations.

Discerning the Mauve Factor, Part 1.

"Mauve Factor" was once mistaken for kryptopyrrole but is the hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-2-one (HPL). Treatment with nutrients--particularly vitamin B6 and zinc--reduces urinary excretion of HPL and improves diverse neurobehavioral symptoms in subjects with elevated urinary HPL. Heightened HPL excretion classically associates with emotional stress, which in turn is known to associate with oxidative stress. For this review, markers for nutritional status and for oxidative stress were examined in relationship to urinary HPL. In cohorts with mixed diagnoses, 24-hour urinary HPL correlated negatively with vitamin B6 activity and zinc concentration in red cells (P < .0001). Above-normal HPL excretion corresponded to subnormal vitamin B6 activity and subnormal zinc with remarkable consistency. HPL correlated inversely with plasma glutathione and red-cell catalase, and correlated directly with plasma nitric oxide (P < .0001). Thus, besides implying proportionate needs for vitamin B6 and zinc, HPL is a promising biomarker for oxidative stress. HPL is known to cause non-erythroid heme depression, which lowers zinc, increases nitric oxide, and increases oxidative stress. Administration of prednisone reportedly provoked HPL excretion in animals. Since adrenocorticoid (and catecholamine) stress hormones mediate intestinal permeability, urinary HPL examined in relationship to urinary indicans, presumptive marker for intestinal permeability. Urinary HPL associated with higher levels of indicans (P < .0001). Antibiotics reportedly reduce HPL in urine, suggesting an enterobic role in production. Potentially, gut is a reservoir for HPL or its precursor, and stress-related changes in intestinal permeability mediate systemic and urinary concentrations.