Patients undergoing recurrent CT exams: assessment of patients with non-malignant diseases,reasons for imaging and imaging appropriateness

To determine percent of patients without malignancy and ≤ 40 years of age with high cumulative radiation doses through recurrent CT exams and assess imaging appropriateness. From the cohort of patients who received cumulative effective dose (CED) of ≥ 100 mSv over a 5-year period, a sub-set was identified with non-malignant disease. The top 50 clinical indications leading to multiple CTs were determined. Clinical decision support (CDS) system scores were analyzed using a widely adopted standard of 1–3 (red) as “not usually appropriate,” 4–6 (yellow) “may or may not be appropriate,” and 7–9 (green) “usually appropriate.” Clinicians reviewed patient records to assess compliance with appropriate use criteria (AUC). 9.6% of patients in our series were with non-malignant conditions and 1.4% with age ≤ 40 years. CDS scores (rounded) were 2% red, 38% yellow, 27% green, and 33% unscored CTs. Clinical society guidelines for CT exams, wherever available, were followed in 87.5 to 100% of cases. AUCs were not available for several clinical indications as also referral guidelines for serial CT imaging. More than half of CT exams were unrelated to follow-up of a primary chronic disease. We are faced with a situation wherein patients in age ≤ 40 years require or are thought to require many CT exams over the course of a few years but the radiation risk creates concern. There is a fair number of conditions for which AUC are not available. Suggested solutions include development of CT scanners with lesser radiation dose and further development of appropriateness criteria.     

Neorickettsia helminthoeca associated lymphoid,enteric, and pulmonary lesions in dogs from Southern Brazil: An immunohistochemical study

Neorickettsia helminthoeca (NH), the agent of salmon poisoning disease or canine neorickettiosis (CN), is a bacterial endosymbiont of the nematode Nanophyetus salmincola, and infections are spreading among specific fish‐eating mammalians. This article describes the pathologic and immunohistochemical findings associated with spontaneous NH‐induced infections in dogs from Southern Brazil. The principal pathologic findings were hypertrophy of Peyer patches and lymphadenopathy with lymphocytic proliferation, chronic interstitial pneumonia, and chronic enteritis associated with positive intralesional immunoreactivity to antigens of NH within macrophages and histiocytes. Positive immunoreactivity against canine parvovirus‐2 (CPV‐2) or/and canine distemper virus was not detected in the evaluated intestinal segments or in the samples from the cerebellum and lungs, respectively, from the dogs evaluated. These findings demonstrated that NH was involved in the enteric, pulmonary, and lymphoid lesions herein described, and provide additional information to confirm the occurrence of this bacterial endosymbiont within this geographical location. It is proposed that chronic pneumonia should be considered as a pathologic manifestation of NH‐induced infections. Additionally, our results show that the occurrences of CN seem to be underdiagnosed in Southern Brazil due to the confusion with the incidence of CPV‐2.     

Symptoms During or Shortly After Isolated Carpal Tunnel Release and Problems Within 24?hours After Surgery

This study used the National Survey of Ambulatory Surgery (NSAS) database to measure the incidence of and risk factors for symptoms in the ambulatory surgery center and problems within 24 h after isolated carpal tunnel release (CTR). The NSAS contained records on 400,000 adult patients with carpal tunnel syndrome who were treated with CTR in 2006, based on ICD-9 codes. The type of anesthesia used and factors associated with symptoms and problems were sought in bivariate and multivariable statistical analyses. The mean duration of the procedure was 16 ± 8.8 min. Only 5 % were performed under local anesthesia without sedation, 45 % with IV sedation, 28 % regional anesthesia, and 19 % general anesthesia. Symptoms in the ambulatory surgery center or a problem within 24 h after discharge were recorded in 10 % of patients, all of them minor and transient, including difficulties with pain and its treatment. The strongest risk factors were male sex, age of 45 years and older, and participation of an anesthesiologist. Local anesthesia and regional anesthesia were associated with more perioperative symptoms and postoperative problems. Most CTR are performed with some sedation in the United States. CTR is a safe procedure: one in 10 patients will experience a minor issue in the perioperative or immediate postoperative period.     

A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer

Lessons Learned

• The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
• Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
• The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.

BackgroundThe RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.MethodsThis was a phase I study with a 3+3 design in patients with treatment‐naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.ResultsA total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose‐limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment‐related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression‐free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated‐ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated‐ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.ConclusionTrametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Esophageal Calibration with Soft Orogasrtric Tube During Laparoscopic Nissen Fundoplication may Reduce Postoperative Transient Dysphagia

Gastroesophageal reflux is the most common benign disorder of the esophagus and laparoscopic Nissen fundoplication has become the standard surgical treatment for its treatment. In our area, where the use of bougie calibration is debatable, postoperative dysphagia is encountered often after this surgery although it is usually not permanent. The aim of this study was to investigate the effect of using a soft silicone tube 39 F in diameter for esophageal calibration during laparoscopic Nissen fundoplication on the incidence of postoperative dysphagia. We divided cases scheduled to undergo laparoscopic Nissen fundoplication between January 2009 and November 2010 into two groups, each consisting 25 patients. Esophageal calibration with a 39 F silicone orogastric tube was used for the first group while there was no operative calibration in the second group. The surgical duration was recorded; the presence and severity of the postoperative dysphagia was calculated by using a dysphagia severity scoring system during the 1-year postoperative follow-up. The dysphagia severity scores were significantly lower in group 1 than group 2 on the postoperative second day and at the end of the first week and first month. We did not find a significant difference at the end of the 6-month and first year. There was also no significant difference regarding surgery duration. The use of a soft orogastric tube 39 F in diameter for esophagus calibration during laparoscopic Nissen fundoplication has significantly decreased the incidence of postoperative transient dysphagia without affecting the duration of surgery. Although dysphagia gradually resolves in the majority of patients, a safe and easy calibration method for its prevention is worth developing, and we believe that the use of our method in larger series could be beneficial.     

Priming sentence comprehension in aphasia: effects of lexically independent and specific structural priming

Background & Aims: Impaired message-structure mapping results in deficits in both sentence production and comprehension in aphasia. Structural priming has been shown to facilitate syntactic production for persons with aphasia (PWA). However, it remains unknown if structural priming is also effective in sentence comprehension. We examined if PWA show preserved and lasting structural priming effects during interpretation of syntactically ambiguous sentences and if the priming effects occur independently of or in conjunction with lexical (verb) information.

Methods & Procedures: Eighteen PWA and 20 healthy older adults (HOA) completed a written sentence-picture matching task involving the interpretation of prepositional phrases (PP; the chef is poking the solider with an umbrella) that were ambiguous between high (verb modifier) and low attachment (object noun modifier). Only one interpretation was possible for prime sentences, while both interpretations were possible for target sentences. In Experiment 1, the target was presented immediately after the prime (0-lag). In Experiment 2, two filler items intervened between the prime and the target (2-lag). Within each experiment, the verb was repeated for half of the prime-target pairs, while different verbs were used for the other half. Participants’ off-line picture matching choices and response times were measured.

Results: After reading a prime sentence with a particular interpretation, HOA and PWA tended to interpret an ambiguous PP in a target sentence in the same way and with faster response times. Importantly, both groups continued to show this priming effect over a lag (Experiment 2), although the effect was not as reliable in response times. However, neither group showed lexical (verb-specific) boost on priming, deviating from robust lexical boost seen in the young adults of prior studies.

Conclusions: PWA demonstrate abstract (lexically-independent) structural priming in the absence of a lexically-specific boost. Abstract priming is preserved in aphasia, effectively facilitating not only immediate but also longer-lasting structure-message mapping during sentence comprehension.