A Pneumatic-based Mechanism for Inserting a Flexible Microprobe into the Brain

Insertion of flexible microprobes into the brain requires withstanding the compressive penetration force by the microprobes. To aid the insertion of the microprobes, most of the existing approaches employ pushing mechanisms to provide temporary stiffness increase for the microprobes to prevent buckling during insertion into the brain. However, increasing the microprobe stiffness may result in acute neural tissue damage during insertion. Moreover, any late or premature removal of the temporary stiffness after insertion may lead to further tissue damage due to brain micromotion, or inaccuracy in the microprobe positioning. In this study, a novel pneumatic-based insertion mechanism is proposed which simultaneously pulls and pushes a flexible microprobe towards the brain. As part of the brain penetration force in the proposed mechanism is supplied by the tensile force, the applied compressive force, which the microprobe must withstand during insertion, is lower compared to the existing approaches. Therefore, the microprobes with a critical buckling force less than the brain penetration force can be inserted into the brain without buckling. Since there is no need for temporary stiffness increment, the neural tissue damage during the microprobe insertion will be much lower compared to the existing insertion approaches. The pneumatic-based insertion mechanism is modelled analytically to investigate the effects of the microprobe configuration and the applied air pressure on the applied tensile and compressive forces to the microprobe. Next, finite element modelling is conducted, and its analysis results not only validate the analytical results but also confirm the efficiency of the mechanism.

DERMATITIS ULCERATIVA EN RATONES BALB/c Cmedc: REPORTE DE 3 CASOS

Ulcerative dermatitis (UD) is a common and spontaneous condition in mice. The disease is characterized by a pruritic skin lesion, pain and a progressive evolution that often results in ulcerations. Sex, environmental conditions, dietary variation, chronic inflammation, barbering and follicular dystrophy are some predisposing factors for the clinical disease development. The aim of this study was report 3 cases of UD in BALBc/Cmedc mice from Center for Comparative Medicine, gross and histopathological lesions were described, and a review about relevance of UD in laboratory mice was made. These cases were characterized by dermatitis, ulcerative and proliferative, chronic, moderate, with neutrophils, hemorrhage and a serocellular crust. Although initial lesions may be mild, lesions in UD typically are unresponsive to treatment and euthanasia is often warranted in severe cases. This is the reason why UD is an important clinical issue that often affects biomedical research by causing problems in mice health and premature removal of animal from laboratory studies.

65 Complication rate of cuffed versus uncuffed PICC lines placed by interventional radiology in pediatric patients

Primary Subject area Paediatric Radiology Background Peripherally inserted central catheters are commonly used in pediatrics to offer stable access for administering prolonged courses of antibiotics, chemotherapy, parenteral nutrition, or other intravenous fluids. Objectives To assess the complication rates of cuffed versus uncuffed PICCs in a pediatric tertiary referral centre. Design/Methods Research ethics board approval was sought and granted. A dual arm study design was employed with a retrospective chart review of PICCs inserted between June 2017 - June 2018, and a prospective chart review of PICCS inserted between January 2019 - June 2019 at a large tertiary pediatric referral center. Data collected from the electronic record included age, weight, and diagnosis. Line type, size, location, insertion and removal dates, and indications were recorded. Primary outcome was removal of PICC after completion of therapy or premature removal due to the following complications: infection, thrombosis, or mechanical failure (defined as catheter breakage, blockage, or dislodgement). Results The study included 266 patients. Across all patients weighing < 10 kg, 90.5% of those with cuffed PICCs and 65% of those with uncuffed catheters completed therapy. The predominant complication resulting in premature removal was mechanical failure, but this was only observed in patients with uncuffed catheters (25%). Infection was also observed only in uncuffed catheters (10%), and thrombosis (4.8%) was only in the cuffed lines. For patients weighing ≥ 10 kg, 86% of those with cuffed PICCs and 77.2% with uncuffed catheters completed therapy. More complications were observed in uncuffed catheters (infection 7.7%, mechanical failure 6.6%, thrombosis 5%). Infection resulting in premature removal occurred in 7% of cuffed catheters. There was no reported mechanical failure or thrombosis in the cuffed group. The distribution of diagnoses was relatively homogenous between the groups for most diagnoses. However, there was a higher percentage of oncology patients in the uncuffed group (23%) than the cuffed group (7%) due to the need for power-injectable lines, which were not available in a cuffed variant during this study. Conclusion All-cause pediatric PICC-associated complications rate in the neonate group for patients < 10kg in the uncuffed group is 35% and in the cuffed group is 4.8%. Whereas in the pediatric group ≥ 10kg, all-cause pediatric PICC-associated complications rate in the uncuffed group is 19.3% and in the cuffed group is 7%. There were no mechanical complications in the cuffed group and the vast majority of lines made it to completion of therapy. This work supports utilization of cuffed PICC lines in selected pediatric patients.

TUNNELED ADULT PERIPHERALLY INSERTED CENTRAL CATHETER (PICC) FOR CENTRAL VENOUS ACCESS IN PAEDIATRICS: A SINGLE CENTRE EXPERIENCE

Objective: Long term intravenous access in paediatrics is challenging in terms of ease of procedure, maintenance of catheter and complications. Small calibre of peripheral veins in children make insertion of peripheral long-term access difficult. Our centre adopted the use of tunneled adult Peripherally Inserted Central Catheter (PICC) for central venous access in paediatrics with the hope to improve these challenges. We describe a single institute 3-year experience of this technique. Material & Methods: Retrospective analysis of patients aged less than 12 years old who had tunneled PICC insertions from January 2018 till December 2020. The following data was recorded and studied: indication, reason for removal, duration of PICC, vessel inserted, device type and complications. Results: Eleven adult PICCs were inserted from this technique in 10 children. The average age was 35.7months and weight was 13.2kg. The youngest patient was 3 months old at 6.9kg. Most common indication for insertion was for long term antibiotics (82%) and the remainder were for difficult intravenous access. The procedure was done under local anaesthetic with sedation in 90% of cases. Average duration of PICC was 26.8 days. Out of 11 PICCs only 1 had line related infection that required premature removal of the catheter. 55% completed the intended duration while 27% of PICCs had dislodged. Conclusion: Tunnelled adult PICC for central venous access in paediatrics is a feasible option for long term vascular access and has a lower risk of infection. However, almost a third of the catheters inserted still suffered premature dislodgement.

THE PREVALENCE OF SECONDARY DENTO-MAXILLAIRE DEFORMITIES ASSOCIATED WITH UNCOMPENSATED DENTITION DEFECTS IN CHILD POPULATION

The aim is to determine the prevalence of dentition defects and secondary dento-maxillaire deformities in different periods of formation of the dento-maxillary system among the child population of Kyiv and the need for their therapeutic and prophylactic prosthetics, assess the level of prosthodontics care provided to them. Materials and methods. To determine the prevalence of dento-maxillary anomalies, dentition defects, and secondary dento-maxillary deformities, we examined 2276 children and adolescents aged 4 to 17 years in educational institutions in Kyiv for the 2017-2018 period. Results of the research. The prevalence of dento-maxillary anomalies among child population is 65.2%. Angle class I holds first place with 45,8% (among the anomalies of individual teeth), Angle class II comes second with 15,2%, the third place is occupied by Angle class III with 4,2%. Secondary dento-maxillary deformities caused by the early loss of both permanent and especially temporary teeth have become more common among the child population. The main reason for their occurrence is timely uncompensated dentition defects, which was confirmed by mass examinations of children aged 4 to 17 years in schools and kindergartens. Dentition defects of various sizes and localization were observed in 359 out of 2276 children, which is 15.8% of the total number of those examined. Tooth loss is most often caused by caries, its complications, and trauma, a little less often – by retention and anodontia. Secondary dento-maxillary deformities (dento-maxillary lengthening of teeth that have lost their antagonists; the inclination of the teeth towards the defect with displacement) were found in 278 children, which amounted to 12.2% of the total number of examined children, and 77.4% of the detected dentition defects (359 children). The obtained data indicate deterioration in the organization and implementation of oral cavity sanitation among the child population, which requires immediate measures to implement programs aimed at early identification and prevention of severe morphological and functional disorders of the dentition. Conclusions. The results of the obtained findings show a high prevalence of dento-maxillary anomalies among the child population – 65.2% (1484 people), and only 34.8% (792 people) had no orthodontic pathology. Dentition defects were diagnosed in 359 people, which is 15.8% of the total number of the examined children. Secondary dento-maxillary deformities were diagnosed in 278 people of the total number of the examined children (2276 people), that is 12.2% of the total number of the diagnosed dentition defects (359 cases) – 77.4%. Most often, secondary deformities occur between 6 and 11 years of age, that is, in the mixed dentition period of occlusion. The main reason for their occurrence was the inefficient prosthesis of dentition defects or its absence. Dentition defects are caused by premature removal of temporary teeth due to complications of caries, trauma, retention, and congenital absence of teeth.

Complications and Management of Totally Implantable Central Venous Access Ports in Cancer Patients at a University Hospital in Oman

Objectives: Totally implantable central venous access ports (port-a-caths) are increasingly used for the safe administration of chemotherapy; however, their use is associated with complications. This study reviews patterns of complications, reasons for premature removal and the duration of the use of port-a-caths in patients receiving cancer treatment at Sultan Qaboos University Hospital (SQUH) and compares the infection rate with the literature and the researchers’ experiences. Methods: This retrospective follow-up study included patients who had received cancer treatment through a port-a-cath and were admitted to SQUH between January 2007 and April 2019. Demographic features, underlying diagnosis, clinical stage, treatment, duration of use and the cause of premature removal of the port-a-cath were recorded. Results: A total of 516 port-a-caths were inserted in 482 cancer patients. The majority of devices were implanted by interventional radiologists (n = 459; 89.0%) and the right internal jugular vein was most frequently accessed (n = 396; 76.7%). The mean indwelling time of a port-a-cath was 288 days (range: 3–1,872 days) for patients with complications and 550 days (range: 7–3,123 days) for patients without complications. Port-a-cath-related infection was the main complication (n = 63; 12.2%). Patient age, gender, treatment intent, underlying diagnosis, clinical stage, chemotherapy regimen, number of treatment courses, operator implanting the port, the type of micro-organism isolated from the port-a-cath and body mass index were significant factors affecting catheter indwelling time (P <0.05). On multivariate analysis, however, none of the factors was found to be significant. Conclusion: Infection was the most common complication necessitating port-a-cath removal. The infection rate was much lower than the researchers’ previous experience and compares favorably with several published reports. KEYWORDS Port-A-Cath; Vascular Access Ports; Catheter-Related Infections; Cancer; Oman.

Spread of COVID-19 through Georgia, USA. Near-term projections and impacts of social distancing via a metapopulation model

Epidemiological forecasts of COVID-19 spread at the country and/or state level have helped shape public health interventions. However, such models leave a scale-gap between the spatial resolution of actionable information (i.e. the county or city level) and that of modeled viral spread. States and nations are not spatially homogeneous and different areas may vary in disease risk and severity. For example, COVID-19 has age-stratified risk. Similarly, ICU units, PPE and other vital equipment are not equally distributed within states. Here, we implement a county-level epidemiological framework to assess and forecast COVID-19 spread through Georgia, where 1,933 people have died from COVID-19 and 44,638 cases have been documented as of May 27, 2020. We find that county-level forecasts trained on heterogeneity due to clustered events can continue to predict epidemic spread over multi-week periods, potentially serving efforts to prepare medical resources, manage supply chains, and develop targeted public health interventions. We find that the premature removal of physical (social) distancing could lead to rapid increases in cases or the emergence of sustained plateaus of elevated fatalities.

AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes

Pyruvate kinase (PK) deficiency is a rare hereditary disorder affecting red cell (RBC) glycolysis, causing changes in metabolism including a deficiency in ATP. This affects red cell homeostasis, promoting premature removal of RBCs from the circulation. In this study we characterized and evaluated the effect of AG-348, an allosteric activator of PK that is currently in clinical trials for treatment of PK deficiency, on RBCs and erythroid precursors from PK-deficient patients. In 15 patients ex vivo treatment with AG-348 resulted in increased enzymatic activity in all patient cells after 24 hours (mean increase 1.8-fold, range 1.2-3.4). ATP levels increased (mean increase 1.5-fold, range 1.0-2.2) similar to control cells (mean increase 1.6-fold, range, 1.4-1.8). Generally, PK thermostability was strongly reduced in PK-deficient RBCs. Ex vivo treatment with AG-348 increased residual activity 1.4 to >10-fold than residual activity of vehicle-treated samples. Protein analyses suggests that a sufficient level of PK protein is required for cells to respond to AG-348 treatment ex-vivo, as treatment effects were minimal in patient cells with very low or undetectable levels of PK-R. In half of the patients, ex vivo treatment with AG-348 was associated with an increase in RBC deformability. These data support the hypothesis that drug intervention with AG-348 effectively upregulates PK enzymatic activity and increases stability in PK-deficient RBCs over a broad range of PKLR genotypes. The concomitant increase in ATP levels suggests that glycolytic pathway activity may be restored. AG-348 treatment may represent an attractive way to correct the underlying pathologies of PK deficiency. (AG-348 is currently in clinical trials for the treatment of PK deficiency. ClinicalTrials.gov: NCT02476916, NCT03853798, NCT03548220, NCT03559699).