Hereditary nonpolyposis colorectal cancer (Lynch syndrome): a review of the literature and case reports

The recent observation of a new HNPCC patient case induced the Authors to review their experience with the syndrome as well as to make an up to date of the problems related to diagnosis, surgical management, surveillance and genetic counselling for such patients with a lifelong high cancer risk. Patients with HNPCC and their first-degree relatives, whose risk of early colorectal carcinoma (especially in the proximal colon) as well as a variety of extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, ureter and renal pelvis) is significantly higher then that of patients with sporadic carcinoma, should be properly managed with surgery and then with endoscopic examination (ideally all life long) starting--in unaffected individuals--at early age (25 years old). Problems related to genetic counselling are considered as well.     

Pharmacologic and Pharmacokinetic Assessment of Anti-TGFβ2 Aptamers in Rabbit Plasma and Aqueous Humor

Purpose The aim of the study is to determine the bioactivity and effects of PEGylation on the pharmacokinetics in rabbit aqueous humor and plasma of an aptamer directed against TGFβ2. Methods Pharmacological activity of anti-TGFβ2 aptamer in rabbit ocular fluid was demonstrated using a mink lung epithelial cell proliferation assay. For pharmacokinetic analyses, concentrations of aptamers in plasma and aqueous humor were determined over time following bilateral subconjunctival administration to Dutch-belted rabbits using a hybridization-based pseudo-enzyme-linked immunosorbent assay (ELISA) assay. Results Anti-TGFβ2 aptamer (ARC81) binds to human TGFβ2 with a K_D of approximately 5 nM and inhibits the activity of human TGFβ2 in vitro in a cell-based assay with an IC₅₀ of approximately 100 nM. ARC81 blocks endogenously derived TGFβ2 in rabbit aqueous humor in vitro with an IC₅₀ of approximately 200 nM and an IC₉₀ of approximately 1 μM. In vivo in rabbit, ARC81 [no polyethylene glycol (PEG)] entered systemic circulation rapidly (t_max = 1 h in plasma) relative to aptamer conjugates ARC117 (20 kDa PEG) and ARC119 (40 kDa PEG), which showed prolonged residence in the subconjunctival space and aqueous compartment (t_max = 6 and 12 h, respectively, in plasma). Both 20- and 40-kDa aptamer conjugates reached maximal concentrations (C_max) in aqueous humor of 23–30 nM and remained at or above 1 nM for as long as 12 h. Conclusions Pharmacologically active levels of anti-TGFβ2 aptamers can be sustained in the ocular fluid and local tissue environment over a 12-h period after single administration. Daily subconjunctival administration of PEGylated anti-TGFβ2 aptamers should allow further pharmacological evaluation of these agents in a rabbit conjunctival scarring model. Perioperative administration, via subconjunctival injection, may prove to be an effective means to deliver therapeutic quantities of TGFβ2 aptamer conjugates in trabeculectomy procedures.     

Apathy and impulsiveness in Parkinson disease: Two faces of the same coin?

Apathy and impulsiveness are 2 common non-motor symptoms in Parkinson disease that could occur in different periods or simultaneously. Apathy and impulsiveness could be interpreted as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, in which, impulsivity, is a result of a hyperdopaminergic state, whereas apathy is viewed as a hypodopaminergic. The study aimed to investigate the presence of impulsiveness and other neuropsychiatric symptoms in Parkinson disease patients with apathy symptoms.Eighty-one patients with Parkinson disease were enrolled in this retrospective study. All subjects were evaluated by the Italian version of the Dimensional Apathy Scale and the Barratt Impulsiveness Scale-version 11, to assess, respectively, apathy and impulsiveness; they were divided into 2 groups (apathy and no apathy). All patients were administered also with questionnaires assessing depressive and anxious symptoms.Statistical analyses showed relevant results. In no-apathy group, education was a significant predictor on impulsiveness (attentional and motor) and apathy (executive and emotional); depression was a significant predictor on planning impulsivity and apathy.This study aimed to consider the importance of apathy and impulsivity in Parkinson disease. Although these are considered as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, these can also occur separately. Moreover, several variables could represent important predictors of apathy and impulsiveness, such as depression. Future investigations should deepen the role of other demographics and psychological variables.     

Stress hyperglycemia is predictive of worse outcome in patients with acute ischemic stroke undergoing intravenous thrombolysis

Journal of Thrombosis and Thrombolysis - No study investigated the possible detrimental effect of stress hyperglycemia on patients affected acute ischemic stroke (AIS) undergoing intravenous...     

Health related quality of life in women with elderly onset rheumatoid arthritis

OBJECTIVE: To examine the association of elderly onset rheumatoid arthritis (RA) with health related quality of life in a population based cohort of older women. METHODS: A nested case-control study of elderly onset RA within the Iowa Women's Health Study (IWHS), a prospective cohort established in 1986 of 41,000 women aged 55 to 69 years. A supplemental questionnaire was mailed to 122 RA cases and 1132 frequency matched controls from the cohort. We used unconditional logistic regression and linear regression to examine the association of elderly onset RA with self-reported measures of functional disability and quality of life. RESULTS: Elderly onset RA was associated with a 6-fold risk (OR 6.0, 95% CI 3.6-10.1) of significant functional disability (Health Assessment Questionnaire score (3) 1). Similarly, elderly onset RA was significantly associated with lower physical component scores of the Medical Outcome Study Short Form-12 (37.2 +/- 10.9 vs 43.6 +/- 11.6; p < 0.001). CONCLUSION: Among a community based cohort, elderly onset RA was strongly associated with functional disability and reduced quality of life. These associations were independent of other age associated factors including depression, recent fracture, and multiple comorbidities.     

Inveterated Facial Palsy Correction with Endoscopically Assisted Multiple Muscle Transposition and Lifts: The EMTL Procedure

Introduction  The aim of the present analysis was to study the safety and efficacy associated with reanimation in facial nerve palsy by the endoscopically assisted multiple muscle transposition and lifts (EMTL). Patients and Methods  The study sample included all patients who had undergone a facial reanimation by EMTL procedure from September 2015 to May 2019. The patients were analyzed retrospectively, with more than 1 year of follow-up, and were evaluated in terms of functional-aesthetic results and postoperative complications. The outcome was evaluated with the Sunnybrook scale. Results  Fourteen patients were included in the present study. They were all inveterate palsies with minimum 4 years from the initial injury. The preoperative Sunnybrook score ranged from 0 to 5 and the postoperative ranged from 30 to 65. Spontaneous smile achievement was obtained in 10 patients and only mild restoration in one patient. The scar and static correction were satisfactory in all patients. Eye protection was improved in all cases with some form of active blinking in six cases. Conclusion  This study showed that facial palsy correction with EMTL procedure offers a promising alternative treatment for patients with facial palsy not suitable for microsurgical muscle transposition.