Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats

Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.     

Invasive diagnostic techniques in idiopathic interstitial pneumonias

Fibrosing interstitial lung diseases (f‐ILDs) represent a heterogeneous group of disorders in which the aetiology may be identified or, not infrequently, remain unknown. Establishing a correct diagnosis of a distinct f‐ILD requires a multidisciplinary approach, integrating clinical profile, physiological and laboratory data, radiological appearance and, when appropriate, histological findings. Surgical lung biopsy is still considered the most important diagnostic tool as it is able to provide lung samples large enough for identification of complex patterns such as usual interstitial pneumonitis (UIP) and nonspecific interstitial pneumonitis. However, this procedure is accompanied by significant morbidity and mortality. Bronchoalveolar lavage is still a popular diagnostic tool allowing identification of alternative diagnoses in patients with suspected idiopathic pulmonary fibrosis (IPF) when an increase in lymphocytes is detected. Conventional transbronchial lung biopsy has a very low sensitivity in detecting the UIP pattern and its role in this clinical‐radiological context is marginal. The introduction of less invasive methods such as transbronchial cryobiopsy show great promise to clinical practice as they can be used to obtain samples large enough to morphologically support a diagnosis of IPF or other idiopathic interstitial pneumonias, along with fewer complications. Recent advances in the field suggest that less invasive methods of lung sampling, without significant side effects, in combination with other diagnostic methods could replace the need for surgical lung biopsy in the future. Indeed, these new multidisciplinary procedures may become the main diagnostic work‐up method for patients with suspected idiopathic interstitial pneumonia.     

CHA<Subscript>2</Subscript>DS<Subscript>2</Subscript>–VASc score predicts short- and long-term outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis

The CHA₂DS₂–VASc score is a validated tool to assess the thromboembolic risk in patients with atrial fibrillation. Pre-stroke CHA₂DS₂–VASc score may predict outcome in patients with acute ischemic stroke (AIS) without atrial fibrillation. The aim of this study was to investigate if the pre-stroke CHA₂DS₂–VASc score is able to predict short- and long-term outcomes in AIS patients treated with intravenous thrombolysis (IVT). The study group consisted of 256 consecutive patients admitted to the Udine University Hospital with AIS and underwent IVT between January 2015 to March 2017. The pre-stroke CHA₂DS₂–VASc score for each patient was calculated from the collected baseline data. Patients were classified into three groups according to their pre-stroke CHA₂DS₂–VASc score: a score of 0 of 1, a score of 2 or 3 and a score above 3. Primary outcome measures were: rate of favorable outcome at 90-days and at 1-year, and mortality at 90-days and at 1-year. Data on functional outcome and mortality 1 year after stroke were collected in 165 patients (65% of the entire sample). Favorable outcome was defined as a modified Rankin Scale score?≤?2. Compared with the CHA₂DS₂–VASc score 0–1 group, patients with higher CHA₂DS₂–VASc scores had a worse outcome and a higher mortality 3 months and 1 year after stroke. The diagnostic performance of the CHA₂DS₂–VASc score as judged with AUC-ROC was 0.70 (95% CI, 0.64–0.76; p?<?0.001) for favorable outcome at 90-days, 0.78 (95% CI, 0.71–0.85; p?<?0.001) for favorable outcome at 1-year, 0.71 (95% CI 0.61–0.79) for mortality at 90-days, 0.73 (95% CI 0.64–0.80; p?<?0.001) for mortality at 1-year. Pre-stroke CHA₂DS_2–VASc score represents a good predictor for short- and long-term outcomes in AIS patients treated with IVT.     

Survey on Neonatal End-of-Life Comfort Care Guidelines Across America

Context

Infants of age less than one year have the highest mortality rate in pediatrics. The American Academy of Pediatrics published guidelines for palliative care in 2013; however, significant variation persists among local protocols addressing neonatal comfort care at the end-of-life (EOL).

Oral Prolonged‐Release Oxycodone/Naloxone for Managing Pain and Opioid‐Induced Constipation: A Review of the Evidence

Background

Opioids provide effective relief from moderate‐to‐severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed‐dose oxycodone/naloxone prolonged‐release tablets (OXN PR) were designed to address the opioid class effect of opioid‐induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse‐deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone.

Methods

A literature search was conducted to assess the evidence base for OXN PR to treat moderate‐to‐severe pain and its impact on bowel function, based on published clinical trials and observational studies.

Results

Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate‐to‐severe cancer‐related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease–related pain. No unanticipated safety concerns have been reported in elderly patients.

Conclusions

Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate‐to‐severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day).     

The presence of melatonin in grapevine (Vitis vinifera L.) berry tissues

Melatonin has been reported in a variety of food plants and, consequently, in a number of plant-derived foodstuffs. In grapevine (Vitis vinifera L.) products, it was found in berry exocarp (skin) of different cultivars and monovarietal wines. Herein, we assessed, by means of mass spectrometry, the occurrence of melatonin in all berry tissues (skin, flesh, and seed) at two different phenological stages, pre-véraison and véraison. We detected the highest melatonin content in skin, at pre-véraison, whereas, at véraison, the highest levels were reported in the seed. Furthermore, during ripening, melatonin decreased in skin, while increasing in both seed and flesh. The relative concentrations of melatonin in diverse berry tissues were somewhat different from those of total polyphenols (TP), the latter measured by the Folin-Ciocalteau assay, and more abundant in seed at pre-véraison and in exocarp at véraison. The highest antiradical activity, determined by both DPPH (2,2-diphenyl-1-pycryl hydrazyl) and ABTS [(2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] radical-scavenging assay, was reported at pre-veráison in seed. To the best of our knowledge, we reported, for the first time, the occurrence of melatonin in grape seeds.     

Impact of emergency medicine faculty on door to thrombolytic time

The objective of this study was to determine the impact of Emergency Medicine (EM) faculty presence on timely thrombolytic therapy for acute myocardial infarction in the Emergency Department (ED). We performed a retrospective study of data regarding acute myocardial infarction patients in the ED of a large urban teaching hospital. Data were collected from January 1, 1998 to December 31, 1999 when EM faculty were not present in the ED and from January 1, 2001 to December 31, 2002 when they were. We compared median time from patient arrival to thrombolytics, percent of patients receiving thrombolytics within 30 min of arrival, and percent of patients with indications for primary revascularization who received it before and after EM faculty presence. The results indicate that EM faculty presence resulted in a decrease in median time from arrival to thrombolytic administration of 17 min (95% CI: 9, 28). Before EM faculty presence, the median time was 44 min as compared to 24 min post-EM faculty presence. Patients received thrombolytic therapy within 30 min 25.8% of the time before EM faculty presence as compared to 65.4% with EM faculty presence; an absolute increase of 39.6% (95% CI: 23.0%, 56.3%). Primary revascularization occurred in 56.9% of eligible patients pre-EM faculty presence and 81.4% post-EM faculty presence; an increase of 24.5% (95% CI: 13.6%, 35.4%). We conclude that the introduction of Emergency Medicine faculty significantly improved the quality of care for acute myocardial infarction patients in a large urban Emergency Department.     

Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum beta-lactamase involved in an outbreak in long-term-care facilities in Toronto, Canada

A major outbreak involving an Escherichia coli strain that was resistant to expanded-spectrum cephalosporins occurred in Toronto and surrounding regions in 2000 to 2002. We report the complete sequence of a plasmid, pC15-1a, that was found associated with the outbreak strain. Plasmid pC15-1a is a circular molecule of 92,353 bp consisting of two distinct regions. The first is a 64-kb region that is essentially homologous to the non-R-determinant region of plasmid R100 except for several point mutations, a few small insertions and deletions, and the absence of Tn10. The second is a 28.4-kb multidrug resistance region (MDR) that has replaced the R-determinant region of the R100 progenitor and consists mostly of transposons or partial transposons and five copies of the insertion element IS26. All drug resistance genes found in pC15-1a, including the beta-lactamase genes bla(CTX-M-15), bla(OXA-1), and bla(TEM-1), the tetracycline resistance gene tetA, and aminoglycoside resistance genes aac(6')-Ib and aac(3)-II, are located in the MDR. The bla(CTX-M-15) gene was found downstream of ISEcp1as part of a transposition unit, as determined from the surrounding sequence. Examination of the plasmids from CTX-M-15-harboring strains isolated from hospitals across Canada showed that pC15-1a was found in several strains isolated from a site in western Canada. Comparison of pC15-1a and pCTX15, found in an E. coli strain isolated in India in 1999, revealed that the plasmids had several features in common, including an R100 backbone and several of the resistance genes, including bla(CTX-M-15), bla(TEM-1), bla(OXA-1), tetA, and aac(6')-Ib.     

Closer: A videoconference intervention for distance caregivers of cancer patients

Distance caregivers (DCGs) represent a growing demographic. The emotional burden of caregiving for a family member with cancer is amplified by the logistical challenges of providing support from afar. DCGs feel higher levels of distress, anxiety, and depression compared with local caregivers. Videoconference technology may alleviate both the emotional and practical burdens faced by DCGs. This is an ongoing randomized controlled trial in 32 outpatient ambulatory clinics at a large, urban, comprehensive cancer center. To date, 332 patient‐DCG dyads have been enrolled. DCGs must have internet access and have been identified by the patient as a source of support. The intervention period is 4 months. DCGs are randomized to one of three arms: DCGs in Arm 1 receive four coaching sessions with an advanced practice nurse or social worker and four videoconference appointments during the oncologist‐patient office visit. DCGs in Arm 2 participate in four videoconference appointments with the oncologist and patient, and Arm 3 is the control group, which receives access to information through a website. Primary outcome variables are DCG distress, anxiety, depression, burden, self‐efficacy, and emotional support. These data are collected electronically at baseline, 4 months, and 6 months. Patient distress, anxiety, and depression are also assessed at these same intervals using brief in‐person interviews. The change in each of the DCG outcomes over time will be examined by a repeated measures analysis of covariance.