The learning curve for transoral incisionless fundoplication

Background and study aims Transoral incisionless fundoplication (TIF) is a safe and effective minimally invasive endoscopic technique for treating gastroesophageal reflux disease (GERD). The learning curve for this technique has not been reported. We studied the learning curve for TIF when performed by a gastroenterologist by identifying the threshold number of procedures needed to achieve consistent technical success or proficiency (consistent creation of TIF valve ≥ 270 degrees in circumference, ≥ 2 cm long) and efficiency after didactic, hands-on and case observation experience. Patients and methods We analyzed prospectively collected data from patients who had TIF performed by a single therapeutic endoscopist within 17 months after basic training. We determined thresholds for procedural learning using cumulative sum of means (CUSUM) analysis to detect changes in achievement rates over time. We used breakpoint analysis to calculate procedure metrics related to proficiency and efficiency. Results A total of 69 patients had 72 TIFs. The most common indications were refractory GERD (44.7 %) and proton pump inhbitor intolerance (23.6 %). Proficiency was achieved at the 18th to 20th procedure. The maximum efficiency for performing a plication was achieved after the 26th procedure, when mean time per plication decreased to 2.7 from 5.1 minutes (P < 0.0001). TIF procedures time varied until the 44th procedure, after which it decreased significantly from 53.7 minutes to 39.4 minutes (P < 0.0001). Conclusions TIF can be safely, successfully, and efficiently performed in the endoscopy suite by a therapeutic endoscopist. The TIF learning curve is steep but proficiency can be achieved after a basic training experience and 18 to 20 independently performed procedures.

Chromosome Aberrations in Lymphocytes of Patients Undergoing Radon Spa Therapy: An Explorative mFISH Study

In the present exploratory study, we aim to elucidate the action of radon in vivo and to assess the possible health risks. Chromosome aberrations were analyzed in lymphocytes of two patients (P1, P2) undergoing radon spa therapy in Bad Steben (Germany). Both patients, suffering from painful chronic degenerative disorders of the spine and joints, received nine baths (1.2 kBq/L at 34 °C) over a 3-week period. Chromosome aberrations were analyzed before and 6, 12 and 30 weeks after the start of therapy using the high-resolution multiplex fluorescence in situ hybridization (mFISH) technique. For comparison, the lymphocytes from two healthy donors (HD1, HD2) were examined. P1 had a higher baseline aberration frequency than P2 and both healthy donors (5.3 ± 1.3 vs. 2.0 ± 0.8, 1.4 ± 0.3 and 1.1 ± 0.1 aberrations/100 analyzed metaphases, respectively). Complex aberrations, biomarkers of densely ionizing radiation, were found in P1, P2 and HD1. Neither the aberration frequency nor the fraction of complex aberrations increased after radon spa treatment, i.e., based on biological dosimetry, no increased health risk was found. It is worth noting that a detailed breakpoint analysis revealed potentially clonal aberrations in both patients. Altogether, our data show pronounced inter-individual differences with respect to the number and types of aberrations, complicating the risk analysis of low doses such as those received during radon therapy.

Case Report: Very Late, Atypical Extra-Medullary Relapse in a Patient With Acute Promyelocytic Leukemia (APL) Rescued With a Transplant-Free Approach

Relapses of acute promyelocytic leukemia (APL) beyond 7 years from the first molecular remission are exceptional, and it is unclear whether these relapses represent a new, therapy-related leukemia rather than a delayed relapse of the original leukemic clone. The increase extra-medullary relapses (ER) in the era of all-trans retinoic acid (ATRA) therapy suggests a potential correlation between ATRA therapy and ER, and several potential explanations have been proposed. The gold standard post-remission approach, particularly for patients in late relapse, has not yet been established. The benefit of a transplant approach has been questioned in this setting because continuing ATRA-arsenic trioxide (ATO) might be curative. Here we report on the case of an APL patient who relapsed 9 years after achieving her first molecular complete remission (mCR) and who showed an atypical isolated localization at nodal sites, including the into- and peri-parotid glands. Genomic PML/RARa breakpoint analysis detected the same bcr3 PML/RARa hybrid gene in DNA purified from bone marrow and lymph nodes, suggesting that the relapse was because of the reemergence of the initial clone. This case shows that APL, treated with ATRA and cytotoxic drugs, may still emerge in extra-medullary sites even after a very prolonged mCR and could be salvaged with an ATO-based protocol, not including a transplant approach.

Breakpoint Analysis for the COVID-19 Pandemic and Its Effect on the Stock Markets

In this research, statistical models are formulated to study the effect of the health crisis arising from COVID-19 in global markets. Breakpoints in the price series of stock indexes are considered. Such indexes are used as an approximation of the stock markets in different countries, taking into account that they are indicative of these markets because of their composition. The main results obtained in this investigation highlight that countries with better institutional and economic conditions are less affected by the pandemic. In addition, the effect of the health index in the models is associated with their non-significant parameters. This is due to that the health index used in the modeling would not determine the different capacities of the countries analyzed to respond efficiently to the pandemic effect. Therefore, the contagion is the preponderant factor when analyzing the structural breakdown that occurred in the world economy.

PATH-17. INTRAGENIC COPY NUMBER BREAKPOINT ANALYSIS OF METHYLATION DATA FROM CNS TUMOURS IDENTIFIES NOVEL SUBGROUP-SPECIFIC CANDIDATE FUSION GENE ENRICHMENTS

Methylation array-based molecular profiling has redefined the classification of brain tumours and now forms an important part of their integrated diagnosis, providing both subgroup assignment and genome wide DNA copy number profiles. These latter data can be used to identify intragenic breakpoints which are frequently associated with structural variations resulting in therapeutically targetable oncogenic fusion genes. To systematically assess the landscape of these alterations, we combined publicly available methylation datasets resulting in a total of 5660 CNS tumours, around half paediatric, and including &gt;1000 high grade glioma and DIPG. These were analysed by standard methodology (MNP, conumee), and intragenic breakpoint enrichment was compared within methylation subgroups, superfamilies, and tumours with no high-scoring classification. Benchmarking included sequence-verified cases such as infant hemispheric gliomas (IHG) with ALK(15%) and ROS1(7%) fusions, and pathognomic alterations associated with specific entities such as RELA-EPN, MYB-LGG and HGNET-MN1. We identified previously unreported enrichments of well-recognised fusion targets such as NTRK2in GBM_MID and NTRK3in DMG_K27 (both 5%), METin A_IDH / A_IDH_HG (3–5%), and FGFR1/3in GBM_G34 (8–9%). Novel recurrent kinase gene candidates to be verified and explored further include IGF1Rin 2–12% cases spanning glioma subgroups, and TIE1in poorly classified tumours. This latter ‘NOS’ group were also enriched in various transcription factor targets of breakpoints, including TCF4and PLAGL2. Despite limitations due to sample quality, resolution or balanced translocations, breakpoint analysis of methylation copy number profiles provides simple screening for structural rearrangements which may directly influence targeted therapy in paediatric CNS tumours.

Distance from the outbreak of infection, ozone pollution and public health consequences of SARS-CoV-2 epidemic

Background Italy was the second country in the world, after China, to be hit by SARS-CoV-2 pandemic. The Italy’s experience teaches that steps to limit people’s movement by imposing “red zones” need to be put in place early by carefully identifying the cities to be included within these areas of quarantine. The assessment of the relationship between the distance from an established outbreak of SARS-CoV-2 infection with transmission-linked cases and mortality observed in other sites could provide useful information to identify the optimal radius of red zones. Methods We investigated the relationship between SARS-CoV-2 cases and the distance of each Italian province from the first outbreak of SARS-CoV-2 epidemic in Italy (the city of Lodi placed in the Lombardia region). In 38 provinces of Lombardia and neighboring regions, we performed a breakpoint analysis to identify the radius of the red zone around Lodi minimizing epidemic spread and mortality in neighboring cities. Results In all Italian provinces a non-linear relationship was found between SARS-CoV-2 cases and distance from Lodi. In an analysis including the provinces of Lombardia and neighboring regions, SARS-CoV-2 cases and mortality increased when the distance from Lodi reduced below 92 km and 140 km, respectively, and such relationships were amplified by ozone (O3) pollution. Conclusions The breakpoint analysis identifies the radius around the outbreak of Lodi minimizing the public health consequences of SARS-CoV-2 in neighboring cities. Such an approach can be useful to identify the red zones in future epidemics due to highly infective pathogens similar to SARS-CoV-2.

Friendships, loneliness and psychological well-being in older adults: A limit to the benefit of increasing the number friendships.

Objectives: To examine the relationship between number of friends and loneliness, depression, anxiety and stress in older adults. Methods: Data were obtained from 335 older adults via completion of an online survey. Measures included loneliness (UCLA Version 3), depression, stress and anxiety (DASS-21). Participants also reported their number of close friends. Results: Regression analysis revealed a negative curvilinear relationship between number of friends and each of the measures tested. Breakpoint analysis demonstrated a threshold for the effect of number of friends on each of the measures (loneliness = 4, depression = 2, anxiety = 3, stress = 2). Discussion: The results suggest that there is a limit to the benefit of increasing the number of friends in older adults for each of these measures. Elucidating these thresholds can enable loneliness and psychological well-being interventions to be more targeted.

Impact of Global Financial Crisis on Indian Handicrafts Exports: A Breakpoint Analysis

After the global economic downturn in 2007–2008, India’s export of principal commodities such as ores and minerals, engineering goods, projects goods and handicrafts products showed insignificant growth rate. The handicrafts sector has been given focal attention in the study due to its worrying insignificant growth and to exploit opportunities for exporters in the global market. This article, in an attempt to examine structural changes in exports of handicrafts product, performed the Chow breakpoint test by setting a break-up year to see if there has been a break in demand. This study contemplates and reflects how Indian handicrafts sector has surpassed its reputation among the diverse consumers in the global market after the global economic crisis and how government interventions have liberated the sector from middling growth to become a major contributor to world consumption. To make the subject more content and lucid to understand, this study has thoroughly accrued, reviewed and analysed several reports and trade data, and it culminates with some policy implication and suggestions to policymakers and entrepreneurs.