Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation

Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.

A multi-professional approach for transition of care at discharge in hyperglycemic inpatients with covid-19: a single center study

Background: The discharge from hospital of insulin-treated hyperglycemic patients is always challenging. This is even more so in patients requiring glucocorticoid treatment, such as those with COVID-19. Patients and method: A retrospective monocentric study of 23 inpatients with newly diagnosed or already known diabetes mellitus (DM) who were naïve to insulin treatment, , and who were hospitalized with COVID-19 in non-critical settings and then discharged. Patients were followed-up for one month after discharge for the management of insulin treatment by a multi-professional team through phone consultations. Results: Insulin prescriptions at discharge were 24.6 ± 14 U/day injected in 2 ± 1.5 daily shots. A mean of three phone consultations were required. One month later, the mean insulin reduction was 1.5 ± 1.3 shots and 6 ± 5 U/day. All patients reached their glycemic target without hypoglycemic events, drop-outs, or readmissions. Conclusion: This study demonstrates the feasibility, efficacy, and safety of a multi-professional approach through telemedicine for managing DM patients after discharge during COVID-19.

Project "Homeopathy for L'aquila" Classical Homeopathy applied in the case of earthquake as a medical assistance plan

Background: The project “Homeopathy for L’Aquila” was developed in order to provide humanitarian and professional assistance to the people of L’Aquila, who were the victims of a devastating earthquake during the night of April 6th, 2009. This project was promoted by the Federazione Italiana Associazioni Medici Omeopati (FIAMO) and supported by the governmental organization for Emergencies (Protezione Civile). Aim: This paper is the report of that experience in the state of absolute emergency, which lasted 17 months. It aims to be a feasibility study as well as a model for further emergencies. Methodology: A medical office was located in a container of 60 square meters which was open from Monday to Friday, beginning in August 2009 and lasting until December 2010. This was provided by Protezione Civile with all the basic equipment, including a reception with a secretary. There were 16 homeopathic physicians and 2 acupuncturists, coming from all over Italy. Every month they rotated to offer free consultations of Classical Homeopathy, as well as Acupuncture and Neuraltherapy. Only people coming from the earthquake area were admitted: all of them signed an informed consent. An operational protocol was defined for the data collection. Each consultation was reported in a special register. The follow-up period lasted 17 months. The protocol consisted of the first consultation and at least 3 control visits, when possible at 30, 60 and 120 day intervals. As a primary outcome the main complaint of the patient was considered in its relation to the quality of life. This evaluation followed a slightly modified criterion of a qualitative scale: Outcome in Relation to Impact on Daily Living (ORIDL). A statistical analysis with some non parametric tests was carried out (Kolmogorof, ). Even the most frequently prescribed homeopathic medicines were taken into consideration. Results: 674 patients were visited from August 2009 to December 2010. In total 1,542 medical visits and treatments were carried out (1,070 as Homeopathy; 280 as Neuraltherapy; 192 as Acupuncture). 366 patients received Classical Homeopathy. The most frequently treated syndromes were of the “psychiatric” type (162 cases=44%), prevalently due to the consequences of the earthquake, such as sleeping disturbances, phobic states, anxious-depressive syndromes, etc. The drop-outs were 235 out of 366 (=64%). 107 patients presented for a minimum 3 follow-ups. Here are the results: cured (52%), major improvement (33%), moderate and slight improvement (12%), no change (3%), deterioration (0%). The statistical analysis (D = 51 > 1,949; = 48,039 > 10,83) showed a significance higher than 1‰. Within this group, 68 patients suffering from psychiatric syndromes, who came for a 3rd follow up, showed a similar trend: cured (50%), major improvement (24%), moderate and slight improvement (19%), no change (7%), deterioration (0%). Also in this case the statistical analysis indicated a significance higher than 1‰ (D = 30 > 1,949). The most frequently prescribed medicines were Pulsatilla, Sepia, Arsenicum Album, Argentum Nitricum and Lycopodium. Discussion: The numerous inconveniences due to the emergency certainly did not permit the usual control visits. Moreover a strict observance of the protocol was not always possible, which could explain such a high number of drop-outs. Those patients who completed the therapy had an incremental improvement in their health between the 1st and the 3rd follow-up visit. In the final analysis a series of “strengths” and “weaknesses” in the project were noted. This knowledge could be helpful for future emergencies. Conclusions: The project “Homeopathy for L’Aquila” allowed, for the first time in Italy, an official implementation of Homeopathy in an emergency plan of great impact, on the one hand; and, on the other hand, made a precious human and professional experience possible. Moreover the results obtained have demonstrated that Homeopathy can play an important role socially as well as therapeutically. To the present date there have neither been internationally recognized guidelines nor publications with similar data concerning emergencies. Therefore this project could represent an important reference point for similar events.

Compulsory and voluntary admissions in comparison: A 9-year long observational study

Background: Few studies, so far, have been specifically designed to highlight the features related to Compulsory Admissions (CA) and Voluntary Admissions (VA) in Italian psychiatric emergency wards. Aims: The main purpose of this observational study was to compare the sociodemographic and clinical characteristics of VA and CA and to explore possible predictors of re-admissions. Methods: During a 6-month Index Period (February, the 1st–July, the 31st 2008) all psychiatric admissions were documented and then followed-up through all available informatic systems for the next 9 years. Results: Out of 390 hospitalizations, 101 (25.9%) were compulsory (CA rate was 2.79 per 10,000 inhabitants per year, mean duration of hospitalizations of 7.33 ± 7.84 days). Diagnoses were recorded for the 325 patients who had been hospitalized during index period: schizophrenic psychoses ([ p = .042], in particular schizophrenia [ p = .027]), manic episode ( p = .044), and delusional disorders ( p = .009) were associated with CA; conversely, the diagnosis of unipolar major depression ( p = .005) and personality disorders ( p = .048) were significantly more frequent in VA. The 325 admitted patients were followed up for 1,801 person-years. No significant differences were found in terms of drop-outs, transferring, and discharge rates, and mortality rates due to both natural causes and suicides. Factors associated with at least one compulsory readmission were younger age and having had a previous CA ( p = .011); conversely having been engaged with psychiatric services for over 1 year prior to index hospitalization was protective for a subsequent CA ( p = .013). Conclusions: After a 40-year old political reform, the current study shows that, in a context of integrated outpatient and inpatient services, engagement with outpatient care may be protective for compulsory rehospitalization.

Training Challenges for Effectively Implementing a Technology Clinical Trial: A Snapshot From PRISM 2.0

Technology interventions can only be adequately assessed for efficacy if participants are adequately trained to use the technology. Only then can an evaluation be made about whether the technology intervention affects the outcome of interest. In the PRISM study, our goal was to teach inexperienced older adults to use either a tablet computer (control) or the PRISM 2.0 system. In this presentation we will discuss the training processes we used for both groups (e.g., segmenting sessions, providing homework, observations), to enable us to evaluate the relative benefits of PRISM for social connectedness. We will describe the training challenges and the need for assessors to be able to troubleshoot technology issues. We will evaluate individual differences in training success and drop-outs to provide insights for other technology intervention studies. Understanding these individual differences can provide guidance for the deployment of new technologies that may benefit health, social interaction, or cognitive engagement.

Characterizing Nonreturning College Students and Their Departure Intentions

Success for 4-year universities is often measured by graduation and retention rates; however, gaps exist in understanding nonreturning students at private institutions. Recent research is helping to build the lexicon of drop-outs, stop-outs, opt-outs, and transfer-outs to inform strategic retention initiatives. Using an action research method, we characterized 1,091 students into designated subclasses and utilized exit interviews, advising notes, and university surveys to theme their departure intentions. Findings reveal transfer-outs to be the largest subclass, with departure reasons being summarized within themes of university experience and fit, health, academic, and financial. Recommendations are made for university administrators and retention offices related to exit survey questions, broadening success metrics, and to focus on specific student characteristic groups.

Longitudinal Rise in Seroprevalence of SARS-CoV-2 Infections in Children in Western Germany—A Blind Spot in Epidemiology?

SARS-CoV-2 infection rates in children and adolescents are often underestimated due to asymptomatic or oligosymptomatic infections. Seroprevalence studies can reveal the magnitude of “silent” infections in this age group and help to assess the risk of infection for children but also their role in spreading the disease. In total, 2045 children and their parents from the Ruhr region were finally included after the exclusion of drop-outs. Seroconversion rates among children of all age groups increased from 0.5% to 8% during the study period and were about three to fourfold higher than the officially registered PCR-based infection rates. Only 41% recalled symptoms of infection; 59% were asymptomatic. In 51% of the infected children, at least one parent also developed SARS-CoV-2 antibodies. Depending on local incidences, the rates of seroconversion rose to different levels during the study period. Although the dynamics of infection within the study cohort mirrors local incidence, the figure of SARS-CoV-2 infections in children and adolescents appears to be high. Reported contact with SARS-CoV-2-infected individuals in the same household carries a high risk of infection.

De-noising Spatial Expression Profiling Data Based on in situ Position and Image Information

Spatial expression profiling (SEP) technologies provide gene expression close to or even superior to single-cell resolution while retaining the physical locations of sequencing and often also providing matched pathology images. However, the expression data captured by SEP technologies suffer from high noise levels, including but not limited to drop-outs as in regular single-cell RNA-sequencing (scRNA-seq). The extra experimental steps for preserving the spatial locations of sequencing could result in even more severe noises, compared to regular scRNA-seq. Fortunately, such noises could be largely reduced by leveraging information from the physical locations of sequencing and the tissue and cellular organization reflected by corresponding pathology images. In this work, we demonstrated the extensive levels of noise in SEP data. We developed a mathematical model, named Sprod, to reduce such noises based on latent space and graph learning of matched location and imaging data. We comprehensively validated Sprod and demonstrated its advantages over prior methods for removing drop-outs in scRNA-seq data. We further showed that, after adequately de-noising by Sprod, differential expression analyses, pseudotime analyses, and cell-to-cell interaction inferences yield significantly more informative results in various biological application settings. In particular, with Sprod, we discovered 3-4 times more RNA transcripts that were actively transported in mouse hippocampus neurons. We also showed that the tumor cells at the tumor-stroma boundaries demonstrate differential transcriptomic features from the tumor cells in the central regions, caused by their interactions with the stroma/immune cells. Overall, we envision denoising by Sprod to become a key first step to empower SEP technologies for biomedical discoveries and innovations.

Abortion Bans and College Drop-Outs

What seems like a resounding victory for pro-life advocates will have an unintended consequence: derailing the educational plans of millions of Americans—women and men.

Evaluation of a custom QIAseq targeted DNA panel with 164 ancestry informative markers sequenced with the Illumina MiSeq

Introduction of new methods requires meticulous evaluation before they can be applied to forensic genetic case work. Here, a custom QIAseq Targeted DNA panel with 164 ancestry informative markers was assessed using the MiSeq sequencing platform. Concordance, sensitivity, and the capability for analysis of mixtures were tested. The assay gave reproducible and nearly concordant results with an input of 10 and 2 ng DNA. Lower DNA input led to an increase in both locus and allele drop-outs, and a higher variation in heterozygote balance. Locus or allele drop-outs in the samples with less than 2 ng DNA input were not necessarily associated with the overall performance of a locus. Thus, the QIAseq assay will be difficult to implement in a forensic genetic setting where the sample material is often scarce and of poor quality. With equal or near equal mixture ratios, the mixture DNA profiles were easily identified by an increased number of imbalanced heterozygotes. For more skewed mixture ratios, the mixture DNA profiles were identified by an increased noise level. Lastly, individuals from Great Britain and the Middle East were investigated. The Middle Eastern individuals showed a greater affinity with South European populations compared to North European populations.