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Objective: To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist., Design: Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP)., Setting: Conducted in the United States at multiple sites., Methods: SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events., Results: Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo)., Conclusions: NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

We report the contents of elements in feathers of Chinstrap penguin (Pygoscelis antarcticus), which had not been informed up to now, such as silver and bromine and others listed as hazardous by the United States Environmental Protection Agency as arsenic, cobalt, chromium, and mercury. Analyses of the element concentrations in feathers, adult and chicken, from Barton Peninsulas at 25 de Mayo (King George) Island, South Shetlands, were made by Instrumental Neutron Activation Analysis. Samarium, lanthanum a, thorium, and uranium concentrations in Chinstrap penguin feathers were below 0.1 mg/kg. This suggests that the elements in feather do not come from atmospheric particles surface deposition. Arsenic (0.120 ± 0.050 mg/kg) and cobalt (0.030 ± 0.020 mg/kg) concentrations were lower than the reports for other colony of Chinstrap penguins, and essential elements as iron (26 ± 12 mg/kg), zinc (78.0 ± 5.3 mg/kg), and chromium (0.51 ± 0.27 mg/kg) were in the same range while Se (2.90 ± 0.65 mg/kg) content were the lowest reported. Mercury (0.43 ± 0.21 mg/kg), chromium (0.210 ± 0.060 mg/kg), and silver (0.083 ± 0.003 mg/kg) in chicks tended to be lower than in adults. Iron, cobalt, and arsenic concentrations in feathers found in this study were the lowest compared to measurements were in several penguin species in Antarctica. These results confirm to feathers like effective indicators for the trace elements incorporated in the penguins and it provide a data set which can adds to the baseline for bioindication studies using feathers.

Several pollutants, which include metals, are present in the Antarctic atmosphere, snow, marine and terrestrial organisms. This work reports the elements incorporated by Usnea sp thalli in Potter Peninsula, 25 de Mayo (King George) Island, South Shetlands, Antarctica. Geological origin was analyzed as possible sources of elements. For this purpose, correlations were done using a geochemical tracer, principal component analysis and enrichment factors were computed. Lithophile elements from particulate matter were present in most of the sampling sites. Bromine, Se and Hg showed the highest enrichment factors suggesting other sources than the particulate matter. Mercury values found in Usnea sp were in the same range as those reported for Deception Island (South Shetlands) and remote areas from the Patagonia Andes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours., Patients and Methods: To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail., Results: Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians., Conclusions: A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The small bowel is the most common site of gastrointestinal metastasis from cutaneous melanoma. Malignant melanoma has a poor prognosis, especially if distant metastases appear. Although rare primary melanoma of the small bowel has been described, more frequently these lesions originate from unknown cutaneous melanoma. Here we report the case of a 58-year-old man with a diagnosis of melanoma of the ileum without evidence of primary cutaneous disease. After 15 years, during the clinical and radiological follow-up, a cutaneous melanoma in the left parietal side of the scalp, probably corresponding to the primary lesion with abdominal node metastasis, was diagnosed. After 6 months of chemotherapy with fotemustine, the patient showed a complete response. At present, he is still alive 18 years after the diagnosis of intestinal metastasis.

Biomphalaria glabrata is a widespread freshwater gastropod mollusc. The easy aquaculture of these organisms allow its use as an accessible tool for contamination bioassays. B. glabrata showed marked metabolic responses when exposed to cadmium, lead and arsenic. Those responses could also affect the reproduction of the snails. Taking into account this hypothesis, B. glabrata were exposed for 96 h (acute laboratory bioassays) to different concentrations of cadmium (0.1, 0.05 and 0 mg/L), lead (0.5, 0.1, 0.05 and 0 mg/L) and arsenic (0.5, 0.1, 0.05 and 0 mg/L). Snails were removed from the aquaria while eggs were left in the same contaminant concentrations. The effect of the assayed toxicants on snail reproduction was registered as the alterations of the total number of laid eggs (TNLE), hatching time and embryonic survival. At 0.10 mg/L cadmium significantly decreased the TNLE (p<0.05) and no embryos survived. The lowest assayed level (0.05 mg/L) of cadmium, delayed the hatching time twice when it was compared with the control group (p<0.01). Lead decreased the TNLE at 0.5 mg/L level (p<0.01). The other assayed doses (0.05 and 0.10 mg/L) also decreased embryonic survival significantly (p<0.05 and p<0.01 respectively) and extended twice the time to hatching (p<0.01). The 0.50 mg/L level killed all embryos. Arsenic at all studied concentrations decreased the TNLE (p<0.05) while the hatching time was increased by 50%. Embryo survival only decreased at the highest level (0.5 mg/L) of arsenic assayed. In summary, the acute exposure (96 h) to cadmium lead and arsenic, altered the reproduction of B. glabrata, modifying the TNLE, hatching time and embryonic survival.

Surgery alone is currently still accepted as the principal therapy for cure for patients with localized non-small cell lung cancer. The optimal therapy in locally advanced and unresectable stage III disease remains unclear. The limited performance of each single therapeutic strategy (surgery, radiotherapy, or chemotherapy) in the treatment of locally advanced non-small cell lung cancer accounted for the rationale of the many attempts at improvement by integrating the different approaches. In recent years, to improve clinical outcome, chemotherapy or chemoradiation followed by surgery, and definitive chemoradiation have commonly been used. Despite numerous phase-II trials, little evidence from randomized phase-III trials has been generated. The ongoing randomized trials will probably provide more reliable indications to define the management of the large number of patients with locally advanced disease.

Intrahepatic cholestasis involves impaired excretion of bile via the hepatobiliary system as a consequence of one or more lesions within the liver. In humans, intrahepatic cholestasis most often results as a side-effect of drug therapy and the clinical manifestation of this condition, jaundice, has been estimated to account for hospitalization in 2 to 5% of the cases for the general population and approaches as much as 20% in the elderly. With the aging of the population and the common occurrence of poly-drug therapy in geriatric patients, it is to be expected that jaundice due to drug-induced intrahepatic cholestasis will become even more prevalent, and accordingly the need to understand the basic mechanisms of this disease condition will become more urgent. The list of culprit agents implicated in the induction of intrahepatic cholestasis in humans is continually expanding. These include various steroid hormones, bile acids, drugs and other chemicals. Experimentally, a wide spectrum of agents has been shown to precipitate intrahepatic cholestasis. Over the years, a number of hypotheses on the biochemical and pathological mechanisms of intrahepatic cholestasis has emerged, including the following: impaired sinusoidal membrane function; interference with the distribution and binding of cytoplasmic endogenous carrier proteins; interference with mitochondrial energy supply; defects in the canalicular membrane including altered Na+/K+ -ATP-ase activity; impairment of microfilament and microtubule functions; interference with bile secretion involving bile acid dependent and independent fractions, and altered bile acid metabolism due to "hypoactive hypertrophic smooth endoplasmic reticulum". In partial agreement with the latter hypothesis, our studies indicated that impairment of the endoplasmic reticulum might represent one of the early stages in the development of intrahepatic cholestasis. Various experimental conditions that induce intrahepatic cholestasis to different degrees resulted in an interference of the synthesis of microsomal phospholipids and altered microsomal function. The conditions included the administration of various hepatotoxic compounds or steroids, pregnancy, delayed development of the endoplasmic reticulum in neonates, and dietary methyl donor or choline deficiency. This review reports the biochemical-pathological mechanisms postulated to be involved in the genesis of intrahepatic cholestasis with specific reference to experimental models of drug-induced intrahepatic cholestasis. The important practical implications of cholestasis are also briefly surveyed.