Adapting therapy with repeated short-infusions to inter individual variability between patients.

Because of the wide inter individual variability between patients and their marked differences in drug response, one of the major issues that arises is adapting the therapy in question to the particular patient. In hospital, it is possible to vary the conditions of intravenous (i.v.) drug delivery by means of short infusions repeated at certain intervals. In this study, review of this process has been presented, and a therapeutic method described. It essentially consists of two stages. The first concerns the time of the first infusion, and the course of drug elimination: from two analyses of the drug concentrations in the blood made at two different times, the pharmacokinetic parameters of the patient are determined. Stage 2 consists of repeated short infusions and the therapy is adapted to the particular patient by varying the conditions involved. Thus, either the amount of the dose based on the rate of infusion or the time interval between the repeated infusions are varied. In order to reach a general solution, master curves are built by using dimensionless numbers as co-ordinates, such as time expressed in terms of the half-life t0.5 of the drug, and the drug concentration at the peaks defined as a fraction of the first unchanged peak concentration.     

Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy

BackgroundThe aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses).MethodsA cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores.ResultsIncreasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022).ConclusionsWhen starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.     

An extensive left subperiosteal frontotemporal orbital abscess and left suppurative pansinusitis with an odontogenic origin

A 28-years-old patient with pansinusitis and orbital abscesses to odontogenic infection origin were present. Treatment, complication and evolution are discussed.     

Incognito: Are Microchimeric Fetal Stem Cells that Cross Placental Barrier Real Emissaries of Peace?

Chimerism occurs naturaly throughout gestation and can also occur as a consequence of transfusion and transplantation therapy. It consists of the acquisition and long-term persistence of a genetically distinct population of allogenic cells inside another organism. Previous reports have suggested that feto-maternal microchimerism could exert a beneficial effect on the treatment of hematological and solid tumors in patients treated by PBSCT. In this review we report the mechanism of transplacental fetal stem cell trafficking during pregnancy and the effect of their long-term persistence on autoimmunity, GVHD, PBSCT, cancer and stem cell treatment.     

Building longitudinal medication dose data using medication information extracted from clinical notes in electronic health records

ObjectiveTo develop an algorithm for building longitudinal medication dose datasets using information extracted from clinical notes in electronic health records (EHRs).Materials and MethodsWe developed an algorithm that converts medication information extracted using natural language processing (NLP) into a usable format and builds longitudinal medication dose datasets. We evaluated the algorithm on 2 medications extracted from clinical notes of Vanderbilt’s EHR and externally validated the algorithm using clinical notes from the MIMIC-III clinical care database.ResultsFor the evaluation using Vanderbilt’s EHR data, the performance of our algorithm was excellent; F1-measures were ≥0.98 for both dose intake and daily dose. For the external validation using MIMIC-III, the algorithm achieved F1-measures ≥0.85 for dose intake and ≥0.82 for daily dose.DiscussionOur algorithm addresses the challenge of building longitudinal medication dose data using information extracted from clinical notes. Overall performance was excellent, but the algorithm can perform poorly when incorrect information is extracted by NLP systems. Although it performed reasonably well when applied to the external data source, its performance was worse due to differences in the way the drug information was written. The algorithm is implemented in the R package, “EHR,” and the extracted data from Vanderbilt’s EHRs along with the gold standards are provided so that users can reproduce the results and help improve the algorithm.ConclusionOur algorithm for building longitudinal dose data provides a straightforward way to use EHR data for medication-based studies. The external validation results suggest its potential for applicability to other systems.     

Endovascular Repair of Innominate Artery True Aneurysm with Extra-Anatomic Revascularization of Right Carotid and Vertebral Arteries — A Case Report

The purpose of this article is to describe the endovascular repair of a large aneurysm of the innominate artery in a patient with a history of chronic renal failure and coronary artery bypass. A 4.5 × 4.8-cm innominate artery aneurysm that extended to the proximal subclavian artery was diagnosed by chest X-ray, computed tomography, computed tomography angiography, and aortic arch angiogram in an 80-year-old man who had problems with his angio access for renal dialysis. Since these aneurysms are potential sources of emboli to the brain, extra-anatomic diversion and revascularization of the right carotid and vertebral arteries were done before endovascular manipulation of the innominate artery. Before discharge, a computed tomography scan showed no evidence of a Type I or major Type II leak. The patient has been doing well as an outpatient. Large innominate artery aneurysms in high-risk patients can be treated successfully by using a combined approach of extra-anatomic revascularization of the right carotid and vertebral artery system, and endovascular repair of the aneurysm. The following paper, published in Volume 14, No. 3 of the journal, was published with an incorrect figure 2. The article is reprinted here with the correct figure. The online version of the original article can be found at     

The effects of synthetic cannabinoids (SCs) on brain structure and function

There is an increasing use of “Novel Psychoactive Substances” containing synthetic cannabinoids worldwide. Synthetic cannabinoids (SC) are highly addictive and cause severe adverse effects. The purpose of our study was to assess whether chronic use of SC alters brain volume and function. Fifteen SC chronic users and 15 healthy control participants undertook an MRI scan to assess brain volume and function while performing a working memory N-back task and a response-inhibition Go-No-Go task. SC users showed impaired performance on the N-back task but not on the Go-No-Go task. They also showed reduced total gray matter volume compared with control participants, as well as reduced gray matter volume in several cortical regions including the middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate cortex and the precuneus. Moreover, SC users showed diminished brain activations in the precuneus, cuneus, lingual gyrus, hippocampus and cerebellum while performing the N-back task. No differences were found in brain activation while performing the response-inhibition task. This is the first study showing overall reduced grey matter volume and specific reduced grey matter volumes in chronic SC users. Furthermore, this study showed for the first time impairment in the neural brain mechanisms responsible for working memory in SC users. Our results of reduced grey matter density and diminished activation during a working memory task in SC users, may suggest vulnerability of the frontal-parietal network in chronic SC users.     

Comparative Investigation of Collagen-Based Hybrid 3D Structures for Potential Biomedical Applications

Collagen is a key component for devices envisaging biomedical applications; however, current increasing requirements impose the use of multicomponent materials. Here, a series of hybrid collagen-based 3D materials, comprising also poly(ε-caprolactone) (PCL) and different concentrations of hyaluronic acid (HA)—in dense, porous or macroporous form—were characterized in comparison with a commercially available collagen sponge, used as control. Properties, such as water uptake ability, water vapour sorption, drug loading and delivery, were investigated in correlation with the material structural characteristics (composition and morphology). Methylene blue (MB) and curcumin (CU) were used as model drugs. For spongeous matrices, it was evidenced that, in contrast to the control sample, the multicomponent materials favor improved sustained release, the kinetics being controlled by composition and cross-linking degree. The other characteristics were within an acceptable range for the intended purpose of use. The obtained results demonstrate that such materials are promising for future biomedical applications (wound dressings and lab models).