This systematic review synthesised the evidence regarding the impact of baseline PET-CT staging on treatment decisions and patient outcomes.CT and staging laparoscopy are routinely used to stage patients with gastric cancer, however the role of Systematic database searches were performed without date restriction. Studies reporting data in patients with gastric adenocarcinoma who underwent radiological staging were included. One reviewer screened titles and abstracts for suitability and two reviewers extracted data from included articles. Primary outcome was the reported change in management after PET-CT. Secondary outcomes were the rates of recurrence and overall survival between patients staged with and without PET-CT. Risk of bias was assessed using the ROBINS-I tool. PROSPERO registration (CRD42022304314).Data from 11 studies recruiting 2101 patients between 2012 and 2021 were included. PET-CT was performed in 1422 patients. Change of management varied between 3% and 29% of cases. No studies compared recurrence or survival rates between patients staged with or without PET-CT. Adenocarcinoma of intestinal subtype tended to be more FDG-avid compared to diffuse or signet-ring subtypes. No randomised data existed, and studies were considered low quality with high risk of bias.Evidence for the additional value of PET-CT in the gastric cancer staging pathway is limited. All studies reported a positive impact by preventing those with undetected metastatic disease on CT undergoing futile surgery. Future national guidelines should consider routine staging PET-CT in gastric cancer.Studies indicated that FDG PET-CT added benefit in gastric cancer staging by detecting more distant metastases, but these studies were generally of low quality and at high risk of bias. Intestinal subtype of gastric adenocarcinoma tended to be more FDG-avid and therefore more distant metastases were subsequently detected. The incidence of gastric cancer has been declining due to improved detection and treatment of H. pylori infections, yet many patients continue to present with metastatic disease which limits available treatment options. Patients are currently offered peri-operative chemotherapy and gastrectomy as standard first-line radical treatment of locally advanced disease.Despite modest improvements in outcome, the overall survival of patients with gastric cancer remains poor, with 5 year survival estimated as 20%. CT has good accuracy for predicting resectability but is known to have suboptimal sensitivity for distant metastatic disease.Current radiological staging pathways rely on staging CT to assess tumour and nodal staging for resectability, and to detect distant metastatic disease, which would preclude any radical treatment. the role of 18F-fluorodeoxyglucose (FDG) PET-CT in gastric cancer is less clear. Concerns regarding the FDG-uptake of the primary tumour, sensitivity of distant metastases, cost, and resource availability have limited clinician’s confidence in this modality. As such, the Royal College of Radiologists (RCR) indications for PET-CT use in the United Kingdom (UK), which were published in 2022, lists gastric cancer as one tumour site in which PET-CT can be considered only when management may be changed by the result. Thus, a few UK centres offer PET-CT for gastric cancer staging, however the majority do not.Unlike oesophagogastric cancer, where positron emission tomography (PET) is routinely recommended for staging all patients deemed to be potentially curable,Staging PET-CT should be made available to all gastric cancer patients if there is evidence of improved clinical outcomes. PET-CT has the potential to reduce the number of patients that undergo futile gastrectomy, which is associated with significant co-morbidity, when distant metastatic disease is undetected on CT. However, the evidence concerning the impact of PET-CT on treatment decisions has not been systematically reviewed before.Therefore, this review aimed to systematically search the literature and synthesise the evidence concerning the role of baseline staging PET-CT in gastric cancer staging. The primary aim was to determine how frequently PET-CT changes patient management by detecting additional disease. The secondary aims were to assess whether PET-CT changed recurrence or survival rates in patients with gastric cancer. and Synthesis Without Meta-Analysis (SWiM) guidelines. This systematic review is registered with PROSPERO (CRD42022304314).This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA)The MEDLINE [OVID], Embase [OVID], Cochrane Library [Wiley], Scopus [Elsevier], Web of Science Core Collection [Clarivate], Cumulative Index of Nursing and Allied Health Literature (CINAHL) [Ebsco], ClinicalTrials.gov, and World Health Organisation (WHO) databases were systematically searched on 25 November 2021. The search strategy was devised using Medical Subject Headings (MeSH) and free-text terms relating to gastric cancer and PET and adapted using the rules and syntax of the other databases. The search was limited to the English language and without date restriction. No filters for study design were applied. A grey literature search was not performed. The full search strategy can be found in Appendix 1.Inclusion criteria for studies were: (1) patients with confirmed histological cell type of adenocarcinoma or signet-ring carcinoma, (2) patients who underwent radiological staging, (3) patients who received either chemotherapy followed by surgery, surgery alone, or palliation, and (4) sufficient follow-up (at least 12 months) to determine clinical outcomes of recurrence and survival. describes intestinal vs diffuse and indeterminate sub-types of gastric adenocarcinoma. The World Health Organisation (WHO) classification describes papillary, tubular, and mucinous sub-types of adenocarcinomas  and signet-ring cell and other poorly cohesive carcinomas (comparable to Lauren diffuse sub-type). In addition, rarer sub-types of gastric carcinoma  are comparable to Lauren indeterminate sub-type. Lauren diffuse and indeterminate sub-types comprise non-intestinal sub-types.The Lauren classificationExclusion criteria were: (1) studies with a mix of primary tumour types where data pertinent to this systematic review could not be extracted, (2) patients with gastric lymphoma or other rare cell types, (3) studies investigating oesophageal or junctional tumours (Siewert Type I and II), (4) studies investigating recurrent gastric cancer, and (5) studies that used any PET tracer other than FDG.The title and abstracts of studies retrieved during the search process were screened by one reviewer (KGF) for relevance to this systematic review. Full-text articles were retrieved after screening to check against the eligibility criteria. Studies that met the eligibility criteria were included. Data were independently extracted by two reviewers  from the included articles and inputted into a spreadsheet designed for this review. In cases of disagreement, a consensus was reached after consulting a third reviewer. The data variables that were collected are listed in Appendix 2.The primary outcome was the effect that PET-CT had on changing initial treatment decision plans. Secondary outcomes were the rates of recurrence and overall survival between patients staged with or without PET-CT.Methodological quality of included studies was assessed with the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) tool. to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rate the certainty in evidence for each outcome.Data from individual studies concerning primary and secondary outcomes were synthesised using summary statistics and confidence intervals, where available, across the cohorts of patients with gastric cancer. Meta-analysis was not performed because few high-quality studies existed. Standardised metrics were used to synthesise the data and are presented in tabular format. The standardised metric for the primary outcome, was the percentage of cases in which PET-CT was perceived to change the patient management plan from that originally intended. Heterogeneity between studies and limitations in quality of evidence were highlighted in tables. Pre-specified subgroup analysis compared the proportion of cases in which distant metastatic disease was found on PET-CT. The approach described by Murad et alThe systematic search discovered 4637 records, of which 2084 were duplicates. The titles and abstracts of 2553 studies were screened for inclusion. After screening, 2506 studies were excluded leaving 47 full text articles for review. 5 reported data in either patient cohorts not relevant to this review or from cohorts with mixed tumour types that could not be extracted, 5 had study designs that were not relevant, 4 investigated a new technology or novel tracers, 2 were not in the English language, and 1 was a study protocol . The median ages of the cohorts ranged between 57 and 71 years. Proximal tumours accounted for 249 (11.9%) of gastric cancer patients with the remainder located in the body, antrum, or pylorus. Findlay et al reported that 5.0% of patients had linitis plastica, but no other studies commented on the incidence of this pathology. Most patients were male  and diffuse  Lauren sub-types. Grade of differentiation was classified in 1645 patients. Most adenocarcinomas were poorly differentiated .Five studies and the only multi-centre study included, reported the lowest proportion of cases (3%) where PET-CT changed the management plan , five (16.1%), and nine (18.0%) patients had peritoneal disease undetected by PET-CT, respectively. Gertsen et al found that 73 patients (19%) had a positive staging laparoscopy whereas only 3 patients (0.8%) in the whole cohort had FDG-avid peritoneal metastases on PET-CT. Findlay et al found that peritoneal disease was undetected by PET-CT in 35 patients , but in 20 patients with PET-positive metastases, 13 patients had peritoneal disease that would not have been identified at laparoscopy. No peritoneal metastases were identified by PET-CT in Smyth et al.Six studies found that 93% of intestinal type tumours were PET-positive vs 78% that were non-intestinal types, with a corresponding difference in SUVmax . Similar findings were reported by Findlay et al where the median SUVmax of intestinal tumours was 8.9 (IQR 5.05–15.4) compared with 5.1 (IQR 2.50–8.10) for diffuse type tumours (p < 0.001). A large difference in avidity between intestinal and diffuse sub-type tumours was found by Smyth et al . Moreover, gastric adenocarcinomas with signet-ring morphology tended to have lower FDG uptake. Significantly lower FDG-uptake was found between signet-ring morphology vs papillary (p = 0.001) and tubular (p = 0.0008) adenocarcinoma subtypes. In Filik et al, the mean SUVmax of adenocarcinomas vs signet-ring tumours was 15.16 (3.00–44.60) vs 9.90 (5.50–17.70).All studies reported the number of cases in which the primary tumour was deemed FDG-avid. Bosch et al reported the distribution of metastases depending on the Lauren Classification. Findlay et al found in multi-variable analysis that after consideration of laparoscopy, patients with diffuse sub-type were less likely to have metastases overall (OR 0.86 (95% CI 0.35–2.08)), indicating greater incidence of PET-detected metastases with intestinal sub-type, although this was not statistically significant. Similarly, Bosch et al found that in FDG-avid primary tumours, the intestinal sub-type was more likely to have metastases than non-intestinal sub-types (34% vs  20%). Also, primary tumours with higher SUVmax  were more likely to metastasise. Further, Bosch et al commented that lymph node status prediction was more accurate in intestinal than non-intestinal tumours, though overall sensitivity and specificity was poor . Debiec et al reported that the risk of false-negative PET-CT for distant metastases was significantly higher for diffuse (37.5%) and signet ring (28.6%) sub-types than for intestinal sub-types . Smyth et al found that peritoneal disease was more likely to be detected by laparoscopy than PET-CT in diffuse gastric cancer .Six studiesAll studies were deemed at high risk of bias after evaluating each of the seven domains within the ROBINS-I tool. Further detail regarding the risk of bias assessments is included in Appendix 3.The certainty in evidence for the primary outcome was rated as low quality for each study according to the GRADE framework (Appendix 4). which impacts on overall survival and quality of life. Distant metastatic disease precludes curative treatment in current UK practice. National data have reported a benefit of hepatectomy for gastric cancer liver metastases in retrospective analyses for 1 year  and 5 year mortality  vs no hepatectomy. However, radical treatment of oligometastatic disease is not performed routinely in clinical practice at present. Selection for gastrectomy must improve to optimise patient outcome and experience in a group of patients who historically have poor survival.Disease recurrence in patients with gastric cancer is common following gastrectomy. More than 30% of patients have recurrence within 3 years of curative resection, and the majority (88%) have distant metastases, to 29%. Overall, the proportion of cases where PET-CT was reported to change management tended to be lower in studies with larger cohort sizes, although heterogeneity of data was noted across the included studies.This systematic review has comprehensively summarised the evidence regarding the impact that PET-CT has on patient management in eligible studies. The proportion of cases in which PET-CT changed management varied considerably across studies, ranging from 3% The PLASTIC study investigated the additional value of PET-CT and staging laparoscopy in patients with potentially curable locally advanced gastric cancer and change of management was the primary outcome. PLASTIC recruited 394 patients, of which 384 had PET-CT, and 357 had staging laparoscopy, and reported that 3% and 19% of patients had distant metastatic disease detected by PET-CT and laparoscopy, respectively.Despite all studies being graded as low-quality based on methodological limitations and risk of bias assessment, the Dutch PLASTIC study was the only prospective and multi-centre study. and 100% in the studies included in this systematic review. However, the sensitivity of PET-CT varied considerably between studies from as low as 25%–76.5%. A recurring limitation of the included studies was a lack of robust pathological reference standard in all patients. This is a limitation of many diagnostic test accuracy studies investigating distant metastatic disease. It would be unethical to subject all patients to an invasive biopsy with potential risk of harm to confirm a pathological diagnosis of metastasis that was highly suspected on imaging. Absence of abnormality on imaging will contribute to the true- and false-negative imaging rates, which in turn will affect the estimates of sensitivity and specificity.Overall, the specificity of PET-CT for distant metastases is good, with reported values ranging between 86.5%No randomised data were available for PET-CT in this patient group, and generally, study quality was hindered by a high risk of selection bias, lack of pathological validation, limited clinical follow-up, and absence of documented management change. The evidence for PET-CT use in patients with gastric cancer remains limited. hypothesised that if PET-CT were performed first, 11 of 113 (10%) of patients would have avoided a futile laparoscopy. Estimates of the incidence of PET-positive peritoneal disease were generally poorly reported. The main study to describe the benefits of PET-CT vs the limitations of laparoscopy was Findlay et al, in which PET identified unsuspected metastases in 20 patients (7.2%), in locations notoriously difficult to assess at laparoscopy, such as the lesser sac, and extra-abdominal sites.Routine use of staging PET-CT in gastric cancer may avoid subsequent laparoscopy in a small number of patients and could assist the detection of metastases in difficult locations to assess during laparoscopy. Smyth et al Overall, it remains highly likely that clinicians will elect to continue routine use of staging laparoscopy in locally advanced disease, even after PET-CT, as several studies highlighted the high false-negative rate of PET-CT for peritoneal metastases. All six observational studies reported cases of peritoneal cases not detected by PET-CT. Staging laparoscopy will continue to be beneficial, particularly in the diffuse sub-type, because metastases too small to be resolved by PET are common in anatomical locations that also often abut FDG-avid structures such as liver or bowel.Staging laparoscopy is not without limitations. The sensitivity and specificity of detecting macroscopic peritoneal metastases was 82% (95% CI 70–91%) and 78%  in the PLASTIC study. to 93.5%. Differences in FDG uptake between sub-types of adenocarcinomas have implications for the detection of distant metastatic disease. Results from included studies indicated that intestinal type gastric adenocarcinomas tend to demonstrate higher FDG uptake than non-intestinal subtypes, are more likely to metastasise, and that those metastases are more likely to be detected on PET-CT. Smyth et al reported that metastatic disease in patients with diffuse gastric cancer was more likely to be detected by laparoscopy (87.5%) than PET-CT (12.5%).There was considerable heterogeneity in the overall proportions of primary tumours that were FDG-avid ranging from 67.3%vs those who did not. Whilst a staging investigation is unlikely to directly influence these important outcomes, PET-CT may improve patient selection for radical treatment, and therefore improve overall outcomes. For instance, Findlay et al found that PET refuted metastases suggested on CT in five patients (1.79%). The clinical effectiveness of staging PET-CT in gastric cancer therefore remains unknown.No studies reported the differences in recurrence or survival rates between patients who had staging PET-CT  Of 382 patients in total, a clinically relevant lesion was found in 83 (22%) of the 132 patients with suspected relevant secondary findings, which resulted in additional investigations in 60 patients. A second primary tumour was confirmed in 7 of these 83 patients, although follow-up was not reported in the majority. Detection of incidental findings can introduce further delays into the staging pathway, which is important to be aware of. The PLASTIC study found that the introduction of staging PET-CT increased the length of staging pathway from 17 to 19 days.The PLASTIC study reported the numbers of incidental findings found by staging PET-CT. estimated that the net additional cost of PET-CT was £322.01 per patient and cost £6910.86 to avoid one futile attempt at radical treatment. Although only one, single-centre study, this suggests that PET-CT could be a cost-effective staging investigation. Data from an American healthcare system were reported in Smyth et al who concluded that if PET-CT was performed prior to laparoscopy, an additional saving of $2000 per patient could be made by reducing the need for laparoscopy in those with biopsy-proven metastatic disease.Few health economic data were reported in the included studies. Of direct relevance to the NHS, Findlay et al Therefore, the benefits of PET-CT will increase as smaller metastases are accurately detected. Future studies should aim to prospectively document treatment decisions before and after the intervention of PET-CT. Prospective studies, ideally with randomisation, should compare patient outcomes between groups who receive and do not receive PET-CT to estimate its true clinical effectiveness.This systematic review has synthesised the literature describing the impact of staging PET-CT on the management of patients with gastric cancer. An extensive literature search using robust methodology ensured all relevant studies reporting data pertinent to the aims of the review were captured. However, this systematic review also has some limitations. One reviewer screened the titles and abstracts of identified records for suitability. Meta-analysis was not performed because of the low-quality studies and heterogenous distribution of proportions reported within them. Study design and methodology was generally deemed to be low quality. Publication bias was not assessed but all studies reported a positive effect of PET-CT on change in management. Most studies were single-centre, retrospective in nature, and lacked sufficient detail documenting the treatment decisions made before and after PET-CT. In addition, some PET-CT scanners used during the study periods were non-time-of-flight, which results in less sensitivity and resolution of current PET scanners. Advances in digital PET technology, improved reconstruction, motion correction and the use of artificial intelligence techniques are likely to increase the diagnostic yield of small foci of disease, such as those commonly found in lymph nodes, the peritoneum, and liver.In conclusion, this systematic review has shown that evidence concerning the effectiveness of baseline PET-CT in the staging pathway of patients with gastric cancer is lacking and has identified a gap in knowledge where future research should be targeted. Several observational studies have shown that PET-CT influences management by changing treatment decisions in differing proportions of patients. Future national guidelines should consider the routine use of PET-CT in gastric cancer staging given the importance of preventing futile radical surgery.


Consumption of distressing news media, which substantially increased during the COVID-19 pandemic, has demonstrable negative effects on mental health.This study examines the proximal impact of daily exposure to news about COVID-19 on mental health in the first year of the pandemic.A sample of 546 college students completed daily ecological momentary assessments (EMAs) for 8 weeks, measuring exposure to news about COVID-19, worry and optimism specifically related to COVID-19, hopelessness, and general worry.Participants completed >80,000 surveys. Multilevel mediation models indicated that greater daily exposure to news about COVID-19 is associated with higher same-day and next-day worry about the pandemic. Elevations in worry specifically about COVID-19 were in turn associated with greater next-day hopelessness and general worry. Optimism about COVID-19 mediated the relationship between daily exposure to COVID-19 news and next-day general worry but was not related to hopelessness.This study demonstrates the mental health impact of daily exposure to COVID-19 news and highlights how worry about the pandemic contributes over time to hopelessness and general worry. The uncertain and rapidly changing nature of the pandemic, coupled with shelter-in-place and work-from-home orders in the first year of the pandemic, increased access to and demand for information about COVID-19 . News coCrisis situations prompt information seeking to reduce uncertainty and increase feelings of safety, corresponding to an increase in overall news consumption during the pandemic ,8,10,11.A nationally representative, cross-sectional survey found that consuming news about COVID-19 was associated with greater psychological distress in the week following the implementation of stay-at-home orders in the United States . IndividIn addition to intentional engagement, exposure to COVID-19-related news may be incidental. Due to evolutions in news dissemination across social network platforms, millions are inadvertently exposed to distressing content while engaging with social media for connection, social support, and distraction, limiting the efficacy of web-based coping methods and increasing worry -32. DistCOVID-19 represents an ongoing crisis for which much of the coverage has centered on current and future threats . Given tThe proximal mental health impact of daily exposure to news about COVID-19 may generalize over time. Cross-sectional research indicates that greater exposure to COVID-19 media across various platforms is associated with higher levels of both general anxiety and anxiety specifically about COVID-19, although the relationship between the 2 forms of anxiety is not yet understood . EngaginLower levels of optimism have been found to predict greater psychological distress among adults during COVID-19, and the previous literature indicates that higher levels of pessimism are related to a broad range of mental and physiological difficulties -38. FurtEngaging with news that decreases optimism about COVID-19 may contribute to broader psychiatric symptoms, including worry and hopelessness. International research has found that hopelessness, which is associated with lower optimism about the future ,42, has This research is among the first to use real-time monitoring within the context of COVID-19 and, to the best of our knowledge, the only paper to examine the impact of daily exposure to news about COVID-19 on mental health among undergraduate students. Undergraduate students may be particularly vulnerable to the mental health impact posed by the pandemic, given displacement due to campus closures, reduced access to in-person social networks, and uncertainty about graduation and future employment opportunities ,47,48. GThe primary research questions, context, and hypotheses were as follows:What is the impact of daily exposure to news about COVID-19 on mental health? Daily levels of worry and optimism about COVID-19 were assessed over an 8-week study period in the early months of the pandemic. Previous research conducted with this sample indicates that COVID-19 worry and anxiety are significantly higher than general, nonspecific anxious feelings among undergraduates . Given pWhat are mechanisms through which exposure to news about COVID-19 increases mental health issues? Momentary levels of hopelessness and general worry were examined over the same 8-week period. Previous findings indicate that specific worry can generalize following news consumption  and thatData (N=546) were drawn from an ongoing study assessing stress, emotion, and behavior among a general college student sample. Recruitment took place between April and December 2020 following the initiation of stay-at-home orders. Participants were remotely recruited via the undergraduate psychology research pool and introductory courses at a large, public university. Recruitment was open to all students who met eligibility criteria, which were assessed using an online screener. Eligible individuals were aged 18+ years, had access to a smartphone compatible with EMA survey software (MetricWire), and were willing to complete multiple surveys per day across the study period. Upon completion of an informed consent protocol, eligible participants were asked to complete an online baseline assessment and were provided with instructions for downloading MetricWire, a smartphone app used to deliver EMA surveys for the 8-week period. Compensation was provided for completing the baseline assessment and for each of the EMA surveys completed during the study period, with a possible total of US $141 for completing all study procedures. For further recruitment and compensation details, see Kleiman et al .not at all) to 10 (very much) scale. To capture in-the-moment affect, including hopelessness and general worry, single items adapted from the Positive and Negative Affect Schedule  to 5 (very much).Participants completed 6 EMA surveys daily for 8 weeks; 5 surveys were delivered at random times throughout the day to capture a range of real-time responses. The surveys were brief (under 5 minutes) and asked participants to report their in-the-moment feelings  across a range of affect states  on a 0 (e (PANAS ) were usvery pessimistic) to 5 (very optimistic) scale. Finally, the nightly survey asked participants to share the frequency with which they were exposed to news about COVID-19 across the day  on a scale from 0  to 5 (very much). Questions related to COVID-19 were asked using single items developed for this study.The sixth and final survey delivered each night included items asking participants to reflect back across the day. Nightly surveys included a single-item assessment of optimism about COVID-19 , rated on a 0 , which removed 726 (0.8%) survey responses. Since optimism about the coronavirus outbreak and exposure to COVID-19 news were assessed once per day, momentary variables of interest  were aggregated to create daily average scores for each variable for each participant. Participants who recorded <3 days of EMA data were excluded from analyses, yielding a final sample of 19,888 days of data across 546 participants.Given the hierarchical structure of our data, multilevel mediation analyses were used to test our hypothesis that COVID-19 worry and optimism would mediate the relationship between COVID-19 news exposure and general worry and hopelessness. We aggregated momentary variables to create a daily average for each participant, resulting in a nested structure where daily observations (level 1) were nested within people (level 2). Mediator and outcome variables were examined using intraclass correlation (ICC) to determine the proportion of variance attributable to within-person and between-person differences across the study period. We person-mean-centered all exogenous variables.We conducted 2 multilevel mediation analyses with frequency of exposure to COVID-19 news entered as the predictor, COVID-19 worry and optimism as mediators, and hopelessness and general worry as outcome variables see a and 1b.To account for individual differences, a supplemental model was run with person means for all variables included at level 2 see . To exam2. As recommended by Preacher and Selig [Effect sizes for the direct effects of COVID-19 media exposure on the endogenous variables were calculated using Rnd Selig , 95% Monnd Selig -56.This study was approved by the Rutgers University Institutional Review Board (IRB #: Pro2019002249).Between April 24, 2020, and January 31, 2021, our final sample of 546 undergraduate students completed 80,779 assessments over a total of 19,888 days of data across participants =225.02, P<.001, CFI=0.95, RMSEA=0.047) and second =198.86, P<.001, CFI=0.95, RMSEA=0.044) models demonstrated good model fit.P<.001). Counter to our hypothesis, a higher frequency of news exposure on a given day was also significantly associated with higher levels of same-day optimism about COVID-19 (P<.001). Similar associations were found in the second model (see P<.001), but no relationship was found between frequency of news exposure and next-day optimism about COVID-19 (P=.48).Hypothesis 1 was partially supported by examining the direct effects of changes in the frequency of daily COVID-19 media exposure on worry and optimism about the pandemic. In the first model see a, greateodel see b for theP=.001) but there was no significant direct effect of media exposure on next-day hopelessness (P=.26). Similar results were found for the second model such that news exposure exhibited a significant, albeit close to P=.05, direct effect on next-day general worry (P=.047) but not on next-day hopelessness (P=.16) when accounting for next-day specific worry and optimism.For hypothesis 2, we first examined the direct relationship between COVID-19 news exposure and general worry and hopelessness. In the first model, a significant direct effect was found between increased news exposure and increased next-day general worry (P<.001) and same-day hopelessness (P<.001). Similar results were found for the relationship between COVID-19 worry and next-day general worry (P<.001) and hopelessness (P<.001). COVID-19 optimism was significantly associated with same-day general worry (P<.001) and same-day hopelessness (P=.01). COVID-19 optimism was also associated with lower next-day general worry (P<.001), but no significant relationship was found between COVID-19 optimism and next-day hopelessness.COVID-19 worry was significantly associated with same-day general worry  and next-day hopelessness . Optimism about COVID-19 also mediated the relationship between same-day COVID-19 news exposure and next day general worry , but no significant mediation effect was found for the relationship between news exposure and next-day hopelessness. Similar significant indirect effects were found in the second model such that COVID-19 worry also mediated the relationship between prior-day news exposure and same-day general worry  and same-day hopelessness . Optimism about COVID-19 did not mediate the relationship between news exposure and same-day outcomes.Additional models yielded similar results as the original temporal models. Including person means and examining worst-point daily outcomes rather than daily averages did not meaningfully change the findings  Does greater daily exposure to news media about COVID-19 predict elevations in same-day and next-day worry and pessimism specifically about the pandemic? (2) Do COVID-19 worry and optimism generalize to broader worry and hopelessness?Our first hypothesis was partially supported. Greater daily exposure to news about COVID-19 was associated with elevated same-day and next-day COVID-19 worry. However, greater exposure to COVID-19 news was also associated with elevated same-day optimism about the pandemic, suggesting that engaging with information about COVID-19 may have both proximal beneficial and deleterious effects on mental health. No relationship was found between frequency of media exposure and next-day optimism about the pandemic. Our second hypothesis that COVID-19 worry and optimism would mediate the relationship between COVID-19 media exposure and general worry and hopelessness was also partially supported. In both temporal models, mediation effects were found such that greater COVID-19 worry mediated the relationship between increased news exposure and general worry as well as the relationship between increased news exposure and hopelessness. Both models also yielded significant direct effects between increased news exposure and increased general worry, indicating that consuming more news about the pandemic increases nonspecific worry beyond what is accounted for by the mediation effects of COVID-19 worry.These findings add to a limited body of literature suggesting that specific worry prompted by distressing media generalizes to more diffuse worry . GreaterOptimism about COVID-19 was significantly associated with decreased same-day hopelessness and decreased same-day and next-day general worry. COVID-19 optimism also mediated the relationship between increased news exposure and next-day general worry, suggesting that the protective effects of some news consumption may extend beyond same-day reactions. Across our sample, participants were moderately optimistic about COVID-19, reporting higher daily averages for optimism than all other variables examined. This suggests that college students may maintain a general sense of optimism about the pandemic independent from worry, hopelessness, and media exposure. The observed within-person variability in COVID-19 optimism scores (ICC=0.69) supports the examination of optimism about the pandemic as a state-level variable prone to changes over short periods of hours and days.There was mixed support for the relationship between COVID-19 news consumption and hopelessness. There was no direct effect of COVID-19 news exposure on same-day or next-day hopelessness. Indirect effects, however, were found in both models through COVID-19 worry, indicating that COVID-19 media consumption contributes to hopelessness by increasing COVID-19 worry. Given the uncertainty and limited information about the virus in 2020, perceived helplessness and lack of control may have accompanied worry about COVID-19 and contributed to hopeless feelings. More research is needed to determine the nature of the association between specific worry and hopelessness and to identify other possible mediating factors driving the relationship between hopelessness and exposure to distressing media.This study highlights the potential risks of increased media consumption during the COVID-19 pandemic. Although information-seeking behavior during a crisis may be intended to reduce uncertainty and distressing emotions, these findings suggest that regular exposure to COVID-related media may instead lead to deleterious mental health outcomes by increasing worry about the pandemic, which in turn increases general worry and hopelessness. Daily engagement with news may represent a modifiable clinical target, and coping strategies that minimize exposure to distressing news may be beneficial during and beyond the pandemic.This study also illuminates a potential benefit of COVID-19 news consumption, which increased same-day optimism about the pandemic, which in turn was associated with decreased next-day general worry. Parallel relationships between news exposure and COVID-19 worry and optimism imply that engaging with news about the pandemic contributes to multiple possible outcomes. It is possible that certain types of news stories increase optimism, while others increase worry. It is also possible that frequent news consumption is beneficial for some individuals and harmful for others. During a pandemic in which preventive behaviors  can contribute to individual safety and decrease the spread of the pandemic, worry and optimism may each serve adaptive and maladaptive functions. Elevated worry may contribute to mental health difficulties but may also increase adaptive safety behaviors. Recent research has found that individuals who perceive COVID-19 as a high-risk threat are more likely to engage in protective behavior than individuals who are less worried about the personal risk of the pandemic . OptimisNews coverage and publicly available information about COVID-19 play an important role in perceptions of risk and subsequent preventive behaviors. Previous research has indicated that only specific types of media engagement  are related to preventive behaviors but that COVID-19 news consumption increases anxiety and distress regardless of platform or media source ,26,27. TThe generalization of specific worry highlights opportunities for brief interventions to buffer against the deleterious generalization effects of inadvertent news exposure. Szabo and Hopkinson  found thThere were limitations of this study that should be acknowledged. We assessed daily news exposure using a broad self-report item in the nightly surveys, which limited examination of specific types of news engagement and assessment of when news consumption occurred during the day. COVID-19 optimism and news exposure were assessed retrospectively at the daily level rather than using momentary assessments. Previous findings from this sample indicate that participants report higher anxiety about COVID-19 on days when the number of new COVID-19 cases announced were higher in participants’ state of residence . Future This study had several strengths. It is the largest and most fine-grained study to date on the relationship between frequency of daily news exposure and same-day and next-day mental health outcomes among college students. This study used consecutive days of data collection to test the influence of variables specifically related to COVID-19 on general distress the following day, allowing for longitudinal analysis of proximal effects. The research included data collected early in the pandemic when stressors were most novel, and included a large sample size with >80,000 assessments across 546 participants.Additional research using more comprehensive assessments of media exposure is needed to examine the differential effects of incidental exposure to news about COVID-19  compared to intentional engagement. Collecting more fine-grained data  of media exposure may illuminate a proximal temporal precedent between worry and news exposure, allowing researchers to examine the potentially reciprocal relationship between anxious symptoms and information gathering through news engagement. To promote preventive behaviors and knowledge about the pandemic without impacting mental health, future research should also examine whether certain types of information and news delivery differentially contribute to optimism, worry, and hopelessness.


There is limited knowledge regarding the process of deprescribing psychotropic drugs to people with dementia (PwD) conducted by general practitioners (GP). We investigated the impact of a multicomponent intervention, emphasizing medication reviews, on psychotropic drugs and behavioral and psychological symptoms (BPSD) in home-dwelling PwD and quantified change in patient-GP communication evaluated by their informal caregivers.LIVE@Home.Path is a stepped-wedge closed-cohort cluster randomized controlled trial for people with mild to moderate dementia aged ≥65 and their informal caregivers (dyads) in Norway. Complementary to health care as usual (control condition), municipal coordinators implemented the multicomponent LIVE intervention: Learning, Innovation, Volunteer support, and Empowerment (including medication review by the PwD’s regular GPs). Block-randomization was used to allocate dyads in three groups receiving the intervention sequentially in periods of 6 months duration. Prepandemic data from the first period is reported, resulting in a 1:2 intervention-to-control ratio. Primary outcome was change in psychotropic drug use. Secondary outcomes were changes in BPSD by Neuropsychiatric Inventory and Cornell Scale of Depression in Dementia and patient-GP communication by an adaption of the Clinical Global Impression of Change.n=67; control condition n=170). At baseline, 63% used psychotropic medication regularly: antidementia drugs (47%), antidepressants (13%), hypnotics/sedatives (13%), antipsychotics (5%), and anxiolytics (2%). At 6 months, medication reviews were more frequently conducted in the intervention group compared to control . We found no differences regarding a change in drug use and BPSD. Patient-GP communication enhanced in the intervention group . In the intervention group, control group, and overall sample, the informal caregivers of those who had their medications reviewed reported improved patient-GP communication compared to those who did not.Four hundred thirty-eight dyads were screened, 280 included, and 237 participated at 6 months (intervention group Change in psychotropic drug use and BPSD did not differ, even though patient-GP communication improved with medication reviews. Restricted psychotropic drug use among PwD likely reflects more judicious prescribing practices in recent years. Nevertheless, medication reviews could be cultivated to optimize pharmacologic treatment for this complex population.ClinicalTrials.gov: NCT04043364; registered 15/03/2019.The online version contains supplementary material available at 10.1186/s12916-022-02382-5. The number of people with dementia (PwD) is growing dramatically, and the increased disease burden is impacting health care services and societies worldwide . DementiNon-pharmacological interventions are recommended as the first-line approach to target BPSD , 6. Althn=27,090), Richardson et al. (2020) documented that PwD prescribed with Z-hypnotics were more likely to also receive antipsychotics and antidepressants [n=24,735) demonstrated that community-dwelling PwD using antidepressants or antidementia drugs had higher odds of being prescribed antipsychotic medication [n=22,119) found that indications for use and in-home medication routines for elderly were seldom revised as large-quantum packages of sedatives and hypnotics were frequently issued by general practitioners (GPs) during indirect patient contacts  [n=696) used at least one psychotropic drug at nursing home admission [The combination and long-term use of these drugs warrant special attention. In a population-based sample from England n=27,00, Richardication . Even modication . Anotherdmission . These cdmission . The fredmission . This isdmission .A recent expert opinion concludes that the next step in the deprescribing field should tailor interventions for home-dwelling PwD while also involving their informal caregivers to identify preferences for medication use and overall health . Such inThe multicomponent intervention emphasizing GP conducted medication reviews will reduce psychotropic drug use.This deprescribing process will not change BPSD but improve patient-GP communication.We hypothesize that:This is a substudy of LIVE@Home.Path: a multicenter, stepped-wedge cluster randomized controlled trial investigating if a multicomponent intervention for dyads of home-dwelling PwD and informal caregivers (family members) improves resource utilization and caregiver burden in dementia care . With 80LIVE is an acronym for the multicomponent intervention in which a coordinator facilitated Learning, Innovation, Volunteer support, and Empowerment emphasizing medication reviews. Table .The coordinators were nurses, learning disability nurses, and occupational therapists experienced in dementia care already working in the home-based services of the designated municipalities. In the intervention period, each coordinator served approximately 5–7 dyads in addition to other municipal tasks not affiliated with the trial. The research group held two-day implementation seminars at the start of the intervention period to qualify the coordinators to adapt the intervention to the dyad’s needs through lectures, role-plays, and discussions. Pocket manuals describing core features of the intervention guided coordinators in addressing all the intervention components. The coordinators used checklists to document to which extent they had introduced the dyads to the intervention components. To further standardize and secure implementation, we arranged one-day midway seminars halfway through the 6-month intervention period allowing for discussion of obstacles and pitfalls, and telephone follow-up for the coordinators every 14 daysThe coordinators paid the dyads at least two home visits and made monthly telephone calls during the 6-month intervention period. They provided the dyads with verbal and written information on the intervention components in the context of their municipality Table  and estaWe applied convenience sampling to recruit dyads from geriatric and gerontopsychiatric out-patient clinics, municipal memory teams, and general media with no financial incentives. Dyads were eligible if the PwD was ≥65 years, home-dwelling, and in face-to-face contact with the informal caregiver at least 1 h a week. Dementia, as diagnosed by the health care services, qualified individuals for participation regardless of etiology as long as their Mini-Mental Status Examination (MMSE) score was 15–26 or Functional Assessment Staging (FAST) score was 3–7 , 27, 28.The data collectors at municipal sites  completed a one-day training program arranged by the research team to safeguard blinded and standardized data collection. Instructions were given both verbally and in writing. The researchers were available for answering any questions regarding the assessments and provided technical support, as well as assistance, during data collection. Data were immediately transferred to a secure server using tablets.Changes in the numbers of prescribed psychotropic drugs, both in total and regular use, were calculated from baseline to month 6. The dyads reported all the prescription and over-the-counter medicines and supplements the PwD was currently using. The information was confirmed from prescriptions, drug packages, multi-dose drug dispensing, and/or medical records. All substances listed in the Anatomical Therapeutic Chemical Index (ATC) were classified as drugs . The ideThe Neuropsychiatric Inventory NPI-12) was used to evaluate delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibitions, irritability, aberrant motor behavior, sleep disturbances, and appetite changes over the four preceding weeks at baseline and 6 months . Multipl was usedThe Cornell Scale for Depression in Dementia (CSDD) assessed the depressive symptoms of the past week at baseline and 6 months . The ninThe Clinical Global Impression of Change (CGIC)  was adapAt baseline, dementia etiology was classified following the International Classification of Diseases (ICD-10) , while Mt-test was used to compare the intervention to the control group by changes in 1.) psychotropic drug use and BPSD between time points and 2.) patient-GP communication. Pearson’s chi-squared test was used to evaluate to what extent medication reviews were conducted (reach) as well as determine the attrition rates between groups. Subgroup analyses comparing 1.) characteristics across the intervention and control group, 2.) those who had their medications reviewed to those who did not within (a) the intervention and (b) control groups, and 3.) completers and non-completers were made at baseline using Pearson’s chi-square test for categorical data, the unequal variances t-test for normally distributed data, and the Wilcoxon-Mann-Whitney test for non-normal data. Characteristics are presented by number (n) and percent; mean and standard deviation (SD); and median and interquartile range (IQR), respectively. Two-tailed P values <0.05 were regarded as significant. NPI-12 and CSDD total scores were generated without substitution when >80% of the instruments were answered by the informal caregivers. Otherwise, they were regarded as missing. For all data, missing ranged from 0 to 6% . We performed all analyses with Stata/IC, release 17 .The unequal variances n=86, 36%). Antidementia drugs were the most frequently used psychotropic drug class, being regularly prescribed to 112 (47%) PwD. Psychotropic drugs, apart from antidementia drugs, were regularly prescribed to 69 (29%) PwD, and 12 (5%) used two or more. The median NPI-12 total score was 12 (IQR 4 to 24), and 159 PwD (67%) displayed one domain or more of clinical relevance. Mood was the NPI-12 subsyndrome with the highest median score, namely 4.5 (IQR 0 to 11). The median CSDD total score was 5 (IQR 1 to 9), and 73 (31%) of the overall sample suffered from depressive symptoms of clinical relevance.Of the 438 dyads screened for participation in LIVE@Home.Path, 280 dyads were included from May to November 2019   PwD in the intervention group and 72 (42%) of the controls (01) Fig. . Within t-test  and control group , as well as the overall sample   Fig. .Fig. 4ChP=0.793). In most cases, dyads were lost at follow-up because the PwD was permanently admitted to a nursing home or deceased  were older, had a lower level of functioning by FAST, a higher dependency in daily living activities by PSMS and IADL, and used antidementia drugs less often than the completers (n=237)  to people lost at follow-up due to permanent nursing home care (n=24), the exceptions being higher NPI-12 total score  and the number of NPI-12 domains of clinical relevance .The attrition rates from baseline to 6 months were similar in both groups: 16% in the intervention group and 15% in the control group , in which interdisciplinary case conferences failed to reduce the number of potentially inappropriate drugs (24%) yet increased the use of antidementia drugs [n=700), in which close to 40% used antipsychotics, benzodiazepines, and antidepressants, geriatricians outside the health care system were not able to reduce psychotropic drug use by structural medication assessments [This is the first study to evaluate the impact of GP conducted medication reviews on psychotropic drugs in home-dwelling PwD. Contrary to our primary hypothesis, we detected no impact on prescribing practices, although it was demonstrated that medication reviews reduce the number of psychotropic drugs prescribed in nursing homes , 41. Theia drugs . In a Fiessments . This reessments . In Norwessments . A recenessments . Anotheressments . This ilessments , 46. Theessments .n=599) showed that PwD consulted their GPs less often than other elderly persons receiving municipal health and social care services in Norway between 2009 and 2012 [Our data imply that the GPs conducted medication reviews based on their discretion concerning whether an evaluation would benefit the patient. Better interaction within primary care has been warranted for home-dwelling PwD, as an 18-month-long prospective study , we documented an improvement in activities of daily living in nursing home residents after careful withdrawal of psychotropic drugs, as decided by the physician in discussion with colleagues [Even though we report BPSD levels close to what is reported at admission to nursing homes , earlierlleagues , 18. Witlleagues , we advoAs this substudy concentrates on psychotropic prescribing practices, we considered medication reviews the most active ingredient within the intervention because the GPs can effectuate drug changes immediately. However, we acknowledge that it may be challenging to tease out the effects of single elements in multicomponent interventions and cannot exclude that the other components may exert more delayed effects on deprescribing , 18, 22.The primary strength of this study is that the participants completed assessments compiling validated, well-established and complementary instruments that were blindly and electronically administered by trained and supervised data collectors, securing data quality . A consiWe met COVID-19 related limitations in conducting this study. Due to the dramatically worsening care situation resulting in exacerbating BPSD and impinged trial protocol , 53, 54,This study additionally has non-COVID-19-related limitations. Firstly, our study sample was a convenience sample, and the non-random recruitment of dyads from health care services may limit the generalizability of our findings to people living with dementia somehow attended to and supported by formal and informal caregivers. Secondly, self-reports on medication may limit direct comparisons to other studies relying on data from medical records and registries. Our access was only sufficient to verify current drug consumption, and consequently, we did not inquire for prescriber details, indications, and duration of therapy. Thirdly, we did not explore the GPs’ strategies for conducting medication reviews or evaluating drug therapy, or whether they involved other health care professionals. However, the risk that the GPs to PwD allocated to the control conditions altered their behavior  when being studied is minuscule as they were not yet informed on participation. Fourthly, we did not provide the GPs with formalized collegial support, or integrations for decision support other than the reports and coordinators’ involvement, and we cannot exclude the possibility that a more formalized and rigorous medication review would have yielded a greater reduction in psychotropic drug use. This pragmatic approach likely increases the variability, yet increases the external validity, of our study. Finally, the chance of false-positive findings in the subgroup analyses increases due to multiple testing.Even though psychotropic drug use and BPSD were not affected by the multicomponent intervention, our study shows that patient-GP communication improved with medication review. Implementing medication reviews in routine care could achieve long-term benefits by increasing the continuity of care for this complex patient population. We advise GPs to conduct medication reviews regularly for patients with dementia, even when prescription and follow-up are within current standards; and suggest that they, if possible, should exercise collegial support in their local networks. We recommend that future studies explore medication reviews from the GP perspective to develop integrations for decision support in dementia care.Additional file 1. The role of health care professionals involved in the conduction of the LIVE@Home.Path trial. Description: table.Additional file 2. Baseline characteristics for people with dementia by medication review in the first intervention group of LIVE@Home.Path. Description: table.Additional file 3. Baseline characteristics for people with dementia by attrition during the first 6-month period of LIVE@Home.Path. Description: table.


Based on LVEF recovery, 37 patients (57.8%) were deemed responders. According to multivariate analysis, complete functional revascularization was an independent predictor of a significant EF recovery . At three-year follow-up, lack of LVEF recovery was the only predictor of mortality . Conclusions: Functional complete revascularization is an independent predictor of the recovery of LVEF in patients presenting with AMI who underwent Impella-supported PCI. The recovery of LV function is associated with improved prognosis and could be used to stratify the risk of future events at long-term follow-up.Aim: The aim of our study is to assess the predictors and the prognostic role of left ventricle ejection fraction (LVEF) recovery after Impella-supported percutaneous coronary intervention (PCI) in patients presenting with acute myocardial infarction (AMI). Methods: This retrospective, observational study included patients admitted for AMI who underwent Impella-supported PCI in two Italian high-volume cardiac catheterization laboratories. Only patients who underwent an echocardiographic assessment of left ventricle ejection fraction (LVEF) before the procedure (acute LVEF) and during follow-up (follow-up LVEF) were included in the present analysis. Patients with a baseline LVEF ≥40% were excluded from the present analysis. LVEF recovery was calculated as the difference between follow-up LVEF and acute LVEF. A delta ≥5% was considered significant and was used to define the responder group. Results: From April 2007 to December 2020, 64 consecutive patients were included in our study. A total of 55 patients (86%) received hemodynamic support with Impella 2.5, and 9 patients (14%) with Impella CP. Median LVEF at follow-up was significantly higher compared to baseline (36% (30–42) vs. 30% (24–33),  Acute myocardial infarction (AMI) represents one of the leading causes of morbidity and mortality worldwide, and emergency coronary surgery is seldom offered as an alternative. Moreover, data suggest that the spectrum of comorbidities and the complexity of coronary anatomy of patients presenting to catheterization laboratories has increased . PatientAn emergent strategy to facilitate PCI in this cohort of patients is pre-emptive mechanical cardiac support (MCS) . The aimThe purpose of the present study is to assess the predictors and the prognostic impact of left ventricle ejection fraction (LVEF) recovery after Impella-supported revascularization in patients presenting with AMI, including patients whose status is complicated by cardiogenic shock (CS) or presenting with out-of-hospital cardiac arrest (OOHCA).The present analysis was focused on a series of consecutive patients presenting with AMI, including patients presenting with OOHCA or those whose status was complicated by CS who underwent urgent Impella-protected PCI at the cardiac catheterization laboratories of the Verona University Hospital and the Gemelli University Hospital. Indications for urgent revascularization included ST-elevation myocardial infarction or high-risk non-ST-elevation myocardial infarction in the presence hemodynamic instability, recurrent or refractory chest pain despite medical treatment, life-threatening arrhythmias, or the presence of ST-segment depression > 1 mm in ≥ 6 leads, in addition to ST-segment elevation in aVR and/or V1. According to hospital practice, the need for Impella support was assessed based on a collegial heart-team decision in the catheterization laboratory based on a combination of criteria, including clinical and hemodynamic presentation, the severity of left ventricular dysfunction, and the extension and complexity of coronary artery disease. In order to assess the changes in the LVEF after Impella-supported PCI, the present study included only patients with at least two echocardiographic assessments, including one before the procedure (acute LVEF) and at least one at follow-up (follow-up LVEF). Patients with a baseline LVEF above 40% were excluded. A flow chart of the study protocol is reported in Clinical characteristics, comorbidities, and cardiac medications were collected prospectively in a dedicated database. Follow-up data were obtained through medical interviews and electronic patient records. Preoperative risk assessment was performed using EuroSCORE II scores . Visual Impella 2.5 or Impella CP was implanted upstream of the PCI in all patients. According to manufacturer recommendations, the devices were implanted via a percutaneous transfemoral approach. Peripheral angiography was recommended as guidance to place the devices in consideration of anatomic feasibility . The insertion of a 6–8 Fr sheath followed the femoral artery stick. The “preclosure’’ technique was performed through suture-based hemostatic devices . After the insertion of a dedicated sheath, a diagnostic catheter (6 Fr) was advanced into the left ventricle to position an extra-support guidewire into the left ventricle (LV). Then, the Impella catheter was advanced over the guidewire through the aortic valve into the LV and activated after removing the guidewire.According to revascularization guidelines, PCI was performed by the radial or, in patients with unsuitable access, by a contralateral femoral approach using 6–8 Fr catheters.Drug-eluting stent implantation was the principal PCI technique applied, and lesion debulking with Rotablator as an adjunctive device was used for severely calcified coronary segments.At the end of the PCI, the speed of the Impella was gradually decreased, and the device was removed prior to confirmation of hemodynamic stability. In the case of hemodynamic instability or need for ECMO positioning, the Impella was left on site. Access-artery angiography was performed to confirm hemostasis and to rule out vascular complications, whereas mechanical hemostasis failures were managed by manual compression and compressive bandaging.Heparin (weight-adjusted) was administered intravenously in all patients, and the following boluses were administered to maintain activated clotting time between 250 and 300s.Before and after PCI, drugs were administered according to accepted guidelines and established practice standards, including dual antiplatelet therapy, ace inhibitors, proton pump inhibitors (PPIs), beta blockers, and statins. For the present study, clinical records were carefully evaluated. Based on biochemical analyses, troponin I or T and creatine kinase MB were used as biomarkers to quantify myocardial damage. The access site or bleeding complications were assessed according to Bleeding Academic Research Consortium (BARC) guidelines . ClinicaEchocardiographic examinations were performed by expert operators. Data were retrospectively collected from medical notes. LVEF before the procedure (acute LVEF) was obtained from the echocardiographic assessment systematically performed before the index procedure. LVFE at follow-up (follow-up LVEF) was obtained from the echocardiogram performed as part of routine clinical practice at both institutions. LVEF recovery was calculated as the difference between follow-up LVEF and acute LVEF. Based on previous data, an EF recovery of 5% was considered a significant improvement of LV function ,15 and wp-value < 0.05 was considered statistically significant. After verifying normal distribution by Shapiro–Wilk test, variables were expressed as mean and standard deviation (SD) or as median and interquartile range (IQR) as appropriate. Frequencies were compared using the chi-square test or Fisher’s exact test as appropriate. Continuous variables were compared using the t-test or Mann–Whitney test if not normally distributed. Univariate and multivariate logistic regression analyses were conducted to assess baseline predictors of improvement of EF. Survival was displayed using Kaplan–Meier curves and compared using the log-rank test. The univariable and multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. Statistical analysis was performed using SPSS 26.0 , and a From April 2007 to December 2020, 64 consecutive patients presenting with AMI who underwent Impella-supported PCI were included in our study. Baseline clinical characteristics are reported in p < 0.05). Functional complete revascularization was achieved in 41 cases (64%). The median duration of Impella support was 150 min (115–4206). Successful hemostasis was achieved by inserting a double preimplanted Perclose Proglide in 59.7%, Prostar XL in 17.7%, and three patients underwent surgical closure. Procedural and angiographic characteristics of the study population are reported in According to the Bleeding Academic Research Consortium (BARC) scale, we reported six minor bleeding cases (BARC Type I-II) not requiring a specific treatment. A total of 10 patients presented with major bleeding, of which four presented with BARC type IIIa and 4 had bleeding that required interventions . No major vascular complications were reported as shown in According to the study inclusion criteria, all patients underwent an echocardiogram as part of routine clinical practice at a median of 6 months (1–12 months) after the index procedure. p = 0.013). Accordingly, the revascularization index (RI) was significantly higher , and the post-PCI BCIS-JS was significantly lower in the responder group . Medical therapy was similar between the two groups.An EF recovery of at least 5% was observed in 37 patients (57.8%) (responder group). A comparison of baseline characteristics between the responder and the non-responder group is reported in p = 0.048), functional complete revascularization , higher revascularization index , and lower post-PCI BCIS-JS  were predictors of LVEF recovery at follow-up, as shown in Univariate analysis showed that lower LVEF at baseline (odds ratio (OR): 0.915; 95% confidence interval (CI): 0.838–0.999; p = 0.029). Univariate Cox regression analysis showed that improvement in LVEF at follow-up of at least 5% and LVEF at follow-up were the only predictors of three-year mortality  as shown in At the three-year follow-up, the overall mortality rate was 14.1%. Patients with an EF recovery of at least 5% (responder group) had lower mortality compared to the group in which LVEF remained stable . Kaplan–Meier curves are displayed in The present observational study reports on the predictors and the prognostic role of LVEF recovery after Impella-supported revascularization in patients presenting with AMI with acute myocardial infarction at two experienced Italian centers. Functional complete revascularization was an independent predictor of an EF recovery of at least 5% at follow-up; andAn EF recovery of 5% was associated with a significant survival benefit.The main findings of the present analysis are:p < 0.0001) in a cohort of 175 consecutive patients who underwent high-risk PCI with prophylactic support of the Impella 2.5. Interestingly, improvement in LVEF was greater in patients who underwent a PCI on the last remaining patent conduit or in multivessel disease [p < 0.0001), a significant reduction in heart failure symptoms with an 80% reduction in New York Heart Association (NYHA) classification III/IV at follow-up (54% to 11% p < 0.001), and a significant reduction in anginal symptoms with 99% reduction in Canadian Cardiovascular Society (CCS) classification III/IV at follow-up (70% to 1% p < 0.0001). Our results are consistent with a growing body of evidence demonstrating that protected PCI with Impella is associated with improved LVEF and heart failure symptoms. Maini et al. reported a significant increase in LVEF upon discharge , and complete revascularization is associated with increased LVEF and survival [Our group previously showed that protected PCI with Impella is associated with LVEF improvement in complex, high-risk patients at 90-day follow-up  [n = 465) [n = 296 ), have suggested potential benefits of complete revascularization [n = 706) [The role of complete revascularization in patients with myocardial infarction is still debated. Urgent PCI of the infarct-related artery is imperative; however, the management of non-culprit arteries is controversial. Although multivessel PCI may reduce the burden of global myocardial ischemia and improve myocardial function, on the other hand, it may cause harm due to procedural complications, increased procedural time and contrast volume, and possible ischemia in different territories. In patients with multivessel disease and AMI without CS, the previous trials, i.e., DANAMI-3-PRIMULTI  , PRAMI (n = 465) , and CvLrization . Howevern = 706) ,21 showen = 706) . It is wThe RECOVER IV randomized controlled trial (RCT) will assess whether Impella pre-PCI is superior to PCI without Impella in patients with AMI cardiogenic shock. RECOVER IV will be a prospective, two-arm trial. Patients will be randomized to receive either Impella pre-PCI or other treatment protocols, which may include any kind of non-Impella circulatory support. In our experience, Impella support during high-risk PCI can guarantee coronary and systemic perfusion during periods of myocardial ischemia during prolonged or repeated balloon inflations or atherectomy runs, allowing for complete functional revascularization, which could improve ventricular function and long-term prognosis. n = 1) and during the follow-up (n = 5). The reason for this inclusion criterion was to assess the changes in LV function after revascularization, which, unfortunately, led to the exclusion of patients who died within 30 days or were lost to follow-up . This might also explain the relatively low 3-year mortality of our population (14.1%) compared to our series. Moreover, our analysis did not include a control group. Considering such aspects, the present study results should be considered as hypothesis-generating. The results of the ongoing randomized trial will be key in providing further insights on the subject. We acknowledge several limitations of our analysis. The present work is a retrospective, observational study, collecting data from two large and experienced Italian centers, and patient selection was based on local heart-team decisions. The presented population was enrolled during the learning curve in the management of Impella. Another limitation of our study is the exclusion of patients who did not under an echocardiogram both before (Functional complete revascularization is an independent predictor of recovery of LV function in patients presenting with AMI who underwent Impella-supported PCI. The recovery of LV function is associated with improved prognosis and could be used to stratify the risk of future events upon long-term follow-up.


COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis. The Infectious Diseases Working Group (IDWG) of the Italian Pediatric Hematology Oncology Association network (AIEOP) performed a first description of severity and outcome of SARS-CoV-2 infection in 29 Italian oncological pediatric patients, diagnosed during the first pandemic wave (February–May 2020), reported that only 12 patients were symptomatic, of whom only 3 presented with pneumonia and none presented severe or critical disease or required intensive care admission or died of SARS-CoV-2 infection, whereas the main consequence of the infection was the withdrawal of chemotherapy treatment [SARS-CoV-2 infection and the related disease, named novel coronavirus disease 2019 (COVID-19), represent a severe threat to human health with a marked impact on the economic, social, and working human activities on a global scale . Furtherreatment . ConsideThe IDWG of AIEOP performed a prospective analysis of the clinical characteristics, treatment, and outcome of patients diagnosed of SARS-CoV-2 infection. AIEOP centers were invited to collect data on infected patients since the start of pandemic (March 2020). The present report shows data of patients with confirmed SARS-CoV-2 infection diagnosed from April 2020 to May 2021. This period includes the second and the third wave of the pandemic in Italy, before the approval of COVID-19 vaccines under 18 years of age and the start of vaccination campaign in Italy for children. The AIEOP-participating centers were 24 and represent the entire national territory . Data collection was performed by each local co-investigator trough an anonymized paper case report form. Patients’ follow-up was updated on August 31, 2021. Patients ≤ 18 years of age were included if they have been treated with chemotherapy and/or radiotherapy irrespective of treatment status, or have received SCT, and were diagnosed of SARS-CoV-2 infection confirmed by molecular (RT-PCR) or antigen testing on nasopharyngeal swabs or bronchoalveolar lavage.SARS-CoV-2 infections were classified as asymptomatic and symptomatic. COVID-19 was defined by the presence of fever with or without symptoms or signs of respiratory tract or gastrointestinal tract, or any other organ involvement. On the basis of the clinical, laboratory and radiological characteristics, the severity of COVID-19 was graded as mild , moderate (acute lower respiratory tract infection without hypoxemia), severe , or critical (need of intensive care unit or organ support), according to published criteria .On patients on chemotherapy, SARS-CoV-2 infection was further classified according to the time of occurrence as early or late episode , episode on maintenance, and episode after SCT. Maintenance chemotherapy includes low-medium intensity chemotherapy that follows the phases of induction and consolidation, as expected in the protocols for acute lymphoblastic leukemia and high-risk rhabdomyosarcoma , 14.9/L and severe lymphopenia as absolute lymphocyte count (ALC) < 0.3 × 109/L.Blood count values during the infectious episode were also recorded, including white blood cells (WBC), neutrophils, lymphocytes, monocytes, hemoglobin (Hb), platelets (PLT), and lactate dehydrogenase (LDH). Severe neutropenia was defined as absolute neutrophil count (ANC) < 0.5 × 10Data about management and outcomes were described, including modification of chemotherapy and time to SARS-CoV-2 negativization at nasopharyngeal swab.The study was approved by the Ethics Committee of the participating centers and informed consent was obtained from parents and/or patients, as appropriate. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation  and with the Helsinki Declaration of 1975, as revised in 2008.t-test or Mann–Whitney test. The identification of factors potentially associated with moderate, severe, or critical infection was performed by logistic regression analysis. The factors assessed were age, gender, weight, type of underlying disease, time of occurrence SARS-CoV-2 infection  previous HSCT, severe neutropenia, and antifungal prophylaxis. The median follow-up was computed by using the reverse Kaplan Meier methods. A p-value ≤ 0.05 was considered statistically significant. All p-values are two-sided. All the analyses were performed using the statistical software SAS v. 9.4 .The main characteristics of patients were reported by descriptive statistics. Median, minimum, and maximum values were used for continuous variables, while absolute and percentage frequencies were used for categorical variables. Comparisons between categorical variables were performed by the chi-square or Fisher exact test, as appropriate, while continuous variables were compared by p < 0.0001) (Table 2 support and 5 patients were admitted to intensive care unit. Characteristics of these five patients are described in Table p 0.01). After a median follow-up of 2.1 months (95% CI: 1.8–2.6), 150 patients were alive. Three patients died due to disease progression . No death was related to SARS-CoV-2 infection. No patient experienced SARS-Cov2 reinfection during the study period. The analysis performed to identify possible factors associated with moderate, severe, and critical disease is shown in Table During the study period, 153 patients with SARS-COV-2 infection were recorded. The diagnosis was based on positive nasopharyngeal molecular swab in 145 patients, positive nasopharingeal antigen swab in 2 patients while this information was missing in 6 patients. Infection was asymptomatic in 100 children (65.4%) and symptomatic in 53 (34.6%). Table We herein described the prospective data collection of AIEOP-IDWG regarding the clinical characteristics and outcome of SARS-CoV-2 infections in pediatric hematology oncology patients during the second and third wave of the pandemic in Italy. We reported a favorable outcome of the infection in this category of patients, similarly to the first wave description performed by our group .We prospectively enrolled 153 patients from April 2020 to May 2021. To our knowledge, this is the largest multicenter single-country cohort of pediatric cancer patients with SARS-CoV-2 infection described so far. We collected data from the entire national territory and started the enrollment since the very first phase of the pandemic. Together with the adoption of preventive measures recommended by national health authorities, we initiated a screening program by nasopharyngeal swab for all pediatric cancer patients before allowing them to enter hospital to start chemotherapy or undergoing supportive therapies since February 2020 . All theItaly was the first Western country to deal with COVID-19 outbreak in 2020 and concurrently the first one to adopt strict measures in order to limit the spread of the infection . During In our cohort of 153 children, only 10 (6.6%) suffered from a severe or critical form of COVID-19, while the vast majority of patients was asymptomatic or presented only mild symptoms. Ten patients required oxygen support and five were admitted to intensive care unit. No death was related to SARS-CoV-2 infection during the entire observational period. The Global Registry of COVID-19 in Childhood Cancer (GRCCC) was created at the beginning of the pandemic and collected data from the global community in order to describe disease severity and identify factors associated with severe SARS-CoV-2 infection in pediatric cancer patients. Severe or critical illness was reported in 259/1319 patients (19.9%) with a mortality rate of 3.8%, higher than general pediatric population. Intensive treatment, low ANC and ALC, and World-bank income country status were factors associated to disease severity . VariablThe only factors associated to the presence of symptoms in our cohort were low platelets count and higher LDH levels. The latter could be expression of a stronger inflammatory response related to the infection. Data about platelet count were not available in other studies, while we did not found an association of symptomatic or moderate, severe or critical disease with other blood test values like low ANC and ALC, differently from other reports , 20.We showed that the occurrence of the infection early after the underlying disease diagnosis in patients receiving chemotherapy represents a risk factor for moderate, severe, or critical disease. Also, recipients of SCT presented a higher risk of moderate to critical clinical course. These findings partially confirms data from the global cohort in which patients on active treatment or transplanted presented a higher risk of developing a severe or critical infection, possibly related to a significant immunosuppression level and/or a higher susceptibility to respiratory complications . In our We confirmed that a high percentage of patients underwent therapy withdrawal, as already shown in our previous report . This coIt has to be considered that, even if general pediatric population is known to be affected by a milder clinical course of COVID-19, children can be affected by peculiar severe forms, particularly MIS-C , that, iWe reported a favorable outcome of SARS-CoV-2 infection in pediatric oncology and hematology patients during the first three pandemic waves in Italy. Nevertheless, we showed modification of cancer-directed therapy as a relevant effect of COVID-19 in this category of patients, highlighting the importance of prevention of the infection as well as the need of recommendations in order to standardize the approach to COVID-19 management and chemotherapy protocols continuation. Furthermore, the feasibility and efficacy of vaccination need to be emphasized, also in this fragile category of patients . Our gro