Skuteczna alkoholowa ablacja guza insulinowego trzustki, obserwacja 4-letnia. Opis przypadku i przegląd literatury

Introduction: EUS-guided ethanol ablation of insulinoma is a new method of treatment of this neuroendocrine tumour. Ablation is recommended in patients who are poor surgical candidates or refuse surgery. We present a case of an 81-year-old female with symptomatic insulinoma, treated successfully with EUS-guided alcoholic ablation, along with a literature review including 28 other previously described cases. The effectiveness, safety of the therapy, and technical procedure-related issues are summarised. To the best of our knowledge, this is the first described case of successful insulinoma EUS-guided ablation in Poland. Material and methods: We searched the PubMed/Medline database to identify cases of EUS-guided alcoholic ablation. Our analysis included 14 articles (case reports or case series), with a total of 27 patients and 31 tumours described, published before February 2017. Results: The described tumours were relatively small (mean 13 mm), and the most common location was pancreatic head. The mean ethanol volume injected to the tumour was 1.8 ml and the concentration of infused alcohol varied from 95% to 98%.Side effects were observed in six cases; apart from one, they were mild and self-limiting. There was only one severe adverse event, treated conservatively with success. The median follow-up was 14.4 months (2–55 months). In all described cases ablation led to improvement of the symptoms and normalisation of glycaemia. Conclusions: The EUS-guided alcoholic ablation of insulinoma is a safe and effective method of treatment in patients who are poor surgical candidates and/or refuse surgery. The adverse effects are rare and mild and were observed when the volume of injected ethanol was equal to or above 3.0 ml. However, the data is limited, the follow-up is relatively short, and prospective studies are needed to confirm the long-term effects of treatment. The study shows also that there are important procedural differences (concentration and volume of alcohol, needle gauge, number of sessions) between the endoscopists, which should be specified.Wstęp: Przedstawiono 81-letnią chorą z objawowym guzem insulinowym głowy trzustki. Pacjentka, z uwagi na liczne choroby współistniejące, została zdyskwalifikowana z leczenia chirurgicznego. Leczona diazoksydem, ciągłymi wlewami z glukozy, analogami somatostatyny bez istotnej poprawy(obserwowano działania niepożądane). Następnie pod kontrolą EUS wykonano alkoholową ablację zmiany. Nie obserwowano powikłań. Odstawiono diazoksyd, obserwując normalizację glikemii. Pacjentka w 4-letniej obserwacji pozostaje bez objawów klinicznych hipoglikemii. Według naszej wiedzy jest to pierwszy opisany przypadek skutecznej alkoholowej ablacji guza insulinowego w Polsce. W pracy przeprowadzono przegląd literatury i podsumowanie wcześniej przeprowadzonych i opisanych zabiegów alkoholowej ablacji guzów insulinowych, ze szczególnym naciskiem na skuteczność i bezpieczeństwo, czas obserwacji po leczeniu i szczegóły techniczne przeprowadzenia procedury. Materiał i metody: Przeszukano bazę Pub Med/Medline, aby zidentyfikować opisane przypadki alkoholowej ablacji guza insulinowego trzustki. Do analizy włączono 14 artykułów opublikowanych przed końcem lutego 2017, w których opisano łącznie 27 przypadków i 31 guzów insulinowych. Wyniki: Opisane guzy były stosunkowo małymi zmianami (średnio 13 mm), ich najczęstsza lokalizacją była głowa trzustki. Średnia objętość podawanego alkoholu to 1,8 ml, a stężenie wynosiło 95–98%. Efekty uboczne obserwowano w 6 przypadkach, poza jednym były one łagodne i ustępowały samoistnie. Zaobserwowano tylko jedno poważne powikłanie leczone zachowawczo z sukcesem. Średni czas obserwacji pacjenta wyniósł 14,4 miesiąca (od 2 do 55 miesięcy). U wszystkich opisanych chorych ablacja doprowadziła do ustąpienia objawów i normalizacji glikemii. Wnioski: Alkoholowa ablacja guza insulinowego trzustki pod kontrolą EUS jest bezpieczną i skuteczną metoda leczenia tego guza u pacjentów z przeciwwskazaniami do zabiegu lub takich, którzy nie godzą się na zabieg. Większość powikłań ma charakter łagodny i były one obserwowane, gdy objętość podawanego do guza etanolu przekraczała 3,0 ml. Krótki czas obserwacji pacjentów i niewielka liczba opisanych przypadków, sprawiają że konieczne jest zaplanowanie badań prospektywnych, które mogłyby potwierdzić długoterminowe efekty leczenia. Analiza pokazuje również, że występują istotne różnice pomiędzy endoskopistami w zakresie sposobu przeprowadzenia samej procedury (stężenie i objętość alkoholu, rozmiar igły, liczba sesji). Powinno dążyć się do sprecyzowania sposobu jej wykonania.

Primary care bonus payments and patient-reported access in urban Ontario: a cross-sectional study

BACKGROUND: Rurality strongly correlates with higher pay-for-performance access bonuses, despite higher emergency department use and fewer primary care services than in urban settings. We sought to evaluate the relation between patient-reported access to primary care and access bonus payments in urban settings. METHODS: We conducted a cross-sectional, secondary data analysis using Ontario survey and health administrative data from 2013 to 2017. We used administrative data to calculate annual access bonuses for eligible urban family physicians. We linked this payment data to adult (≥ 16 yr) patient data from the Health Care Experiences Survey to examine the relation between access bonus achievement (in quintiles of the proportion of bonus achieved, from lowest [Q1, reference category] to highest [Q5]) and 4 patient-reported access outcomes. The average survey response rate to the patient survey during the study period was 51%. We stratified urban geography into large, medium and small settings. In a multilevel regression model, we adjusted for patient-, physician- and practice-level covariates. We tested linear trends, adjusted for clustering, for each outcome. RESULTS: We linked 18 893 respondents to 3940 physicians in 414 bonus-eligible practices. Physicians in small urban settings earned the highest proportion of their maximum potential access bonuses. Access bonus achievement was positively associated with telephone access (Q2 odds ratio [OR] 1.18, 95% confidence interval [CI] 0.98-1.42; Q3 OR 1.34, 95% CI 1.10-1.63; Q4 OR 1.46, 95% CI 1.19-1.79; Q5 OR 1.87, 95% CI 1.50-2.33), after hours access (Q2 OR 1.26, 95% CI 1.09-1.47; Q3 OR 1.46, 95% CI 1.23-1.74; Q4 OR 1.77, 95% CI 1.46-2.15; Q5 OR 1.88, 95% CI 1.52-2.32), wait time for care (Q2 OR 1.01, 95% CI 0.85-1.20; Q3 OR 1.17, 95% CI 0.97-1.41; Q4 OR 1.27, 95% CI 1.05-1.55; Q5 OR 1.63, 95% CI 1.32-2.00) and timeliness (Q2 OR 1.29, 95% CI 0.98-1.69; Q3 OR 1.29, 95% CI 0.94-1.77; Q4 OR 1.58, 95% CI 1.16-2.13; Q5 OR 1.98, 95% CI 1.38-2.82). When stratified by geography, we observed several of these associations in large urban settings, but not in small urban settings. Trend tests were statistically significant for all 4 outcomes. INTERPRETATION: Although the access bonus correlated with access in larger urban settings, it did not in smaller settings, aligning with previous research questioning its utility in smaller geographies. The access bonus may benefit from a redesign that considers geography and patient experience

Sequencing of human genomes extracted from single cancer cells isolated in a valveless microfluidic device

Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cancer derived cell lines (LS174T, LS180 and RKO) and fresh colorectal tumors have been individually trapped, their genomes extracted and prepared for sequencing using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources. In addition, most of the reads are correctly paired, with a low percentage of singletons (0.17 ± 0.06%) and we obtain genome coverages approaching 90%. To achieve this high quality, our device design and process shows that amplification can be conducted in microliter volumes as long as the lysis is in sub-nanoliter volumes. Our data thus demonstrates that high quality whole genome sequencing of single cells can be achieved using a relatively simple, inexpensive and scalable device. Detection of genetic heterogeneity at the single cell level, as we have demonstrated for freshly obtained single cancer cells, could soon become available as a clinical tool to precisely match treatment with the properties of a patient's own tumor

Using data science for sustainable development in higher education

Despite the abundance of studies focused on how higher education institutions (HEIs) are implementing sustainable development (SD) in their educational programmes, there is a paucity of interdisciplinary studies exploring the role of technology, such as data science, in an SD context. Further research is thus needed to identify how SD is being deployed in higher education (HE), generating positive externalities for society and the environment. This study aims to address this research gap by exploring various ways in which data science may support university efforts towards SD. The methodology relied on a bibliometric analysis to understand and visualise the connections between data science and SD in HE, as well as reporting on selected case studies showing how data science may be deployed for creating SD impact in HE and in the community. The results from the bibliometric analysis unveil five research strands driving this field, and the case studies exemplify them. This study can be considered innovative since it follows previous research on artificial intelligence and SD. Moreover, the combination of bibliometric analysis and case studies provides an overview of trends, which may be useful to researchers and decision-makers who wish to explore the use of data science for SD in HEIs. Finally, the findings highlight how data science can be used in HEIs, combined with a framework developed to support further research into SD in HE

Single-molecule DNA-mapping and whole-genome sequencing of individual cells

To elucidate cellular diversity and clonal evolution in tissues and tumors, one must resolve genomic heterogeneity in single cells. To this end, we have developed low-cost, mass-producible micro-/nanofluidic chips for DNA extraction from individual cells. These chips have modules that collect genomic DNA for sequencing or map genomic structure directly, on-chip, with denaturation-renaturation (D-R) optical mapping [Marie R, et al. (2013) Proc Natl Acad Sci USA 110:4893-4898]. Processing of single cells from the LS174T colorectal cancer cell line showed that D-R mapping of single molecules can reveal structural variation (SV) in the genome of single cells. In one experiment, we processed 17 fragments covering 19.8 Mb of the cell's genome. One megabase-large fragment aligned well to chromosome 19 with half its length, while the other half showed variable alignment. Paired-end single-cell sequencing supported this finding, revealing a region of complexity and a 50-kb deletion. Sequencing struggled, however, to detect a 20-kb gap that D-R mapping showed clearly in a megabase fragment that otherwise mapped well to the reference at the pericentromeric region of chromosome 4. Pericentromeric regions are complex and show substantial sequence homology between different chromosomes, making mapping of sequence reads ambiguous. Thus, D-R mapping directly, from a single molecule, revealed characteristics of the single-cell genome that were challenging for short-read sequencing