Psychological consequences of myocardial infarction (MI) are substantial, as 4% of all MI patients develop posttraumatic stress disorder (PTSD) and 12% clinically relevant posttraumatic stress symptoms (PTSS). The study investigated the course and development within 12 months of MI-induced PTSS to gain novel insights in potentially delayed response to early trauma-focused counseling aimed at preventing the incidence of MI-induced PTSS.In the MI-SPRINT two-group randomized controlled trial, 190 MI-patients were randomly allocated to receive a single-session intervention of either trauma-focused counseling or an active control intervention targeting the general role of stress in patients with heart disease. Blind interviewer-rated PTSS (primary outcome) and additional health outcomes were assessed at 12-month follow-up.p > 0.05). The only group difference emerged in terms of more severe hyperarousal symptoms in the trauma-focused counseling group in the ITT analysis, but not in the completer analysis.12-month follow-up of outcomes were available for 106 (55.8%) of 190 participants: In the entire sample, one patient  who received trauma-focused counseling developed full PTSD. There was no significant difference between trauma-focused counseling and stress counseling regarding total score of interviewer-rated PTSS (No benefits were found for trauma-focused counseling after 12 months when compared with an active control intervention. PTSD prevalence in the present study was low highlighting a potential beneficial effect of both interventions. Further studies are needed to determine the most accurate approach of counseling. Posttraumatic stress disorder (PTSD) is a mental disorder that may occur in the aftermath of a traumatic or stressful, life-threatening event, involving high intensity of fear of dying, helplessness and loss of control . About 7There is an intriguing line of recent research suggesting that clinically relevant PTSS are predictive of incident cardiovascular disease (CVD) morbidity and mortality and may also worsen cardiovascular prognosis –8. AmongEarly interventions to lower the incidence of MI-induced PTSS are of high relevance but are scarce due to a lack of appropriate interventions for these patients . InterveAlternatively, early interventions after trauma for patients with MI might aim at reducing helplessness, and fear of dying . To achiA recent systematic review and meta-analysis on randomized controlled trials (RCT) of early psychological interventions designed to prevent PTSS found a benefit only if treatment was provided to trauma survivors who were identified as having a high risk of developing clinically significant PTSS based on early predictors of PTSD . PerceivBased on these previous findings, the primary focus of our RCT “Myocardial Infarction-Stress PRevention INTervention (MI-SPRINT)” was to investigate whether the development of PTSS can be reduced by a single counseling session that is administered early on  after MI to patients at high risk to develop PTSD  within a setting of a Coronary Care Unit (CCU) .p = 0.40). Therefore, the aim of the present study was to investigate the development and course of PTSS within 12 months after MI to gain novel insights in potential delayed responses to the intervention beyond 3 months. Additionally, mental and physical health outcomes were analyzed for secondary group comparisons.Our primary hypothesis was that posttraumatic stress levels at the 3-month follow-up would be at least 20% lower in the intervention group than in the control group , 23. ResThis is a secondary analysis of data from 106 participants in the MI-SPRINT RCT who completed the 12-month assessments of interviewer-rated PTSS. The study protocol and the 3-month follow-up of this RCT have previously been published , 23. TheWe invited consecutive patients with verified acute ST-elevation myocardial infarction (STEMI) or non-STEMI, referred for acute coronary care intervention to the Cardiology Department, Bern University Hospital, Switzerland, between February 2, 2013 and September 29, 2015, to participate in the MI-SPRINT trial. Inclusion criteria were age 18 years or older; stable circulatory conditions, and high level of acute distress during MI. Acute distress during MI was assessed using numeric rating scales (scores 0–10) for “pain intensity (during MI),” “fear of dying” and “making sorrows and feelings helpless” .High acute distress during MI was defined a priori on the basis of a score of at least 5 for pain plus at least 5 for fear of dying and/ or helplessness. Exclusion criteria included emergency coronary artery bypass grafting; comorbid disease likely to cause death within 1 year; not fully oriented to situation, person, and place; cognitive impairment per an adapted short version of the Mini-Mental State Examination ; current severe clinical depression according to medical history, suicidal ideations in the previous 2 weeks, inadequate knowledge of German; or current participation in another RCT.www.Randomizer.org) that created a list for the group allocation. The intervention assignment was single-blinded such that the list was available to investigators only after the 12-month follow-up assessment of the last patient.This RCT was a single-blinded 2 parallel group behavioral RCT with 2 active face-to-face interventions of the same duration and attention. The study was performed by the bedside within 48 h after patients had reached stable circulatory conditions within the premises of the coronary care unit. Patients were randomly allocated to trauma-focused counseling (intervention group) or stress counseling (control group). Randomization was performed with an online tool . The booklets were used for interacting with the patient during the counseling session and to deepen specific topics. To get examples of specific topics that could be covered during the 45 min counseling in each group see  risk score was used to determine the risk of post-discharge death and recurrent MI after ACS . DepressAll patients were invited to participate in the outcome assessment 12 months after MI. The assessors of the outcome measures were blinded to group assignments. The primary outcome of the MI-SPRINT trial was the total score of the validated German version of the Clinician-Administered PTSD scale (CAPS) , 30 withp = 0.05 and a beta error level of 20%, the sample size was determined as n = 194 for each group  and the pooled analysis for the overall findings. Independent t-test and Pearson Chi-Square test were used to compare intervention groups on sociodemographic, clinical and psychological variables. A general linear model with group (intervention vs. control) as fixed factor and controlling for sociodemographic  and clinical baseline characteristics  was applied. We conducted the analysis for the primary outcome (CAPS) and all secondary outcomes .Data were analyzed using SPSS 25.0 for Windows  with a two-sided significance level of n = 97) or stress counseling (n = 93). The 3-month follow-up assessment was completed by 154 patients (81·1%). The 12-month follow-up was completed by 106 patients (55.8%). We lost 41 participants due to low funding, bad physical condition, unreachability and 7 patients had died during follow-up. Of all patients completing the 12 months follow-up, 59 (55.7%) were in the trauma-focused counseling group and 47 (44.3%) in the stress counseling group. p = 0.026).A total of 190 patients were randomized to either trauma-focused counseling . The groups only differed in the CAPS hyperarousal score in the ITT analysis, with participants in the trauma-focused counseling group showing more severe hyperarousal symptoms than controls. In all other scores of individual PTSS clusters, the groups did not differ significantly, neither in the ITT analysis nor the completer analysis.In the entire sample, there was one patient  in the trauma-focused counseling group who had developed full PTSD 12 months after MI. However, there was no significant difference between trauma-focused counseling and stress counseling regarding the total score of interviewer-rated PTSS, both in the completer and ITT analysis  developed PTSD while meta-analytic data show that 4% 95% CI, 3–5%) of patients will develop PTSD after MI –5% of pa. So far,Clinical and blinded assessment of MI-induced PTSS by both, clinician-rated PTSS and valid self-rated questionnaires, as well as the RCT design are strengths of this study. The longitudinal design with a follow-up period at 12 months is a further strength.However, some limitations of our study should be mentioned as well. First, this was a single-center study with all of the inherent limitations of such a study design. Hence, generalization of findings to other hospitals and healthcare settings is limited. Second, due to the particular study design, i.e., performing counseling sessions at the emergency department, the counseling protocol had to be interrupted or even part of it postponed when the patient required other urgent examinations or medically indicated interventions, such as a coronary angiography. However, the idea of this approach was to provide a single counseling session explicitly for acute emergency cardiac situations. Finally, patients with severe somatic comorbidities and clinical depression who may be more vulnerable to develop PTSS had to be excluded.To sum up, the findings of our study contribute to a better understanding of the effect of single-session counseling on clinician-rated MI-induced PTSD/PTSS. Particularly, we found that early trauma-focused counseling did not show any significant difference in clinician-rated PTSD/PTSS at 12 months follow-up when compared to an active control intervention in patients at risk to develop MI-induced PTSD. Interestingly, when comparing to previous studies, PTSS severity and prevalence of full PTSD prevalence were notably lower in the present study, suggesting a potential beneficial effect of both interventions. Further studies are needed to determine the most accurate approach of counseling.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Kantonale Ethikkommision Bern, Murtenstrasse 31, 3000 Bern. The patients/participants provided their written informed consent to participate in this study.RK, J-PS, US, JB, and HZ contributed to the development of the study design. US, HZ, JB, RK, RL-M, and MP contributed to the development of the verum and control intervention. AP contributed to the discussion of the manuscript. KL and MP wrote the first draft of the manuscript. All authors critically revised and approved the final manuscript.The MI-SPRINT study is funded by the Swiss National Science Foundation . Additional financial support comes from the Teaching and Research Directorate, Bern University Hospital, Switzerland. The funding bodies had no influence on the study design, in the writing of the manuscript, and in the decision to submit the manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cancer is one of the leading causes of death worldwide, bringing a significant burden to human health and society. Accurate cancer diagnosis and biomarkers that can be used as robust therapeutic targets are of great importance as they facilitate early and effective therapies. Shared etiology among cancers suggests the existence of pan-cancer biomarkers, performance of which could benefit from the large sample size and the heterogeneity of the studied patients. In this study, we conducted a systematic RNA-seq study of 9,213 tumors and 723 para-cancerous tissue samples of 28 solid tumors from the Cancer Genome Atlas (TCGA) database, and 7,008 normal tissue samples from the Genotype-Tissue Expression (GTEx) database. By differential gene expression analysis, we identified 214 up-regulated and 186 downregulated differentially expressed genes (DEGs) in more than 80% of the studied tumors, respectively, and obtained 20 highly linked up- and downregulated hub genes from them. These markers have rarely been reported in multiple tumors simultaneously. We further constructed pan-cancer diagnostic models to classify tumors and para-cancerous tissues using 10 up-regulated hub genes with an AUC of 0.894. Survival analysis revealed that these hub genes were significantly associated with the overall survival of cancer patients. In addition, drug sensitivity predictions for these hub genes in a variety of tumors obtained several broad-spectrum anti-cancer drugs targeting pan-cancer. Furthermore, we predicted immunotherapy sensitivity for cancers based on tumor mutational burden (TMB) and the expression of immune checkpoint genes (ICGs), providing a theoretical basis for the treatment of tumors. In summary, we identified a set of biomarkers that were differentially expressed in multiple types of cancers, and these biomarkers can be potentially used for diagnosis and used as therapeutic targets. Cancer is a serious threat to human life and health and is an important public health problem worldwide. According to the World Health Organization 2021, cancer is the first or second leading cause of human death . Cancer Early detection and accurate diagnosis of cancer based on robust biomarkers are of great value as they dramatically improve the therapeutic outcome . ReducedPINK1 was down-regulated in most tumors and may play a protective role in cancer patients  was associated with poor prognosis and immune infiltration in a variety of cancers . PINK1 wpatients . NFE2L2 n-cancer . Pan-cann-cancer , while dn-cancer . TherebyCurrently, the TCGA  project There are different treatment modalities for each tumor at present, while fewer broad-spectrum anti-cancer drugs are available, and it is urgent to find more broad-spectrum anti-cancer drugs. In addition, except for traditional treatment modalities like chemotherapy, immunotherapy represented by immune-checkpoint inhibitors (ICIs) has significantly improved the survival status of cancer patients, which is now changing the way of cancer treatment. However, the response to ICIs varies dramatically among patients with different malignancies. Therefore, screening the appropriate immunotherapy population before treatment is crucial to achieving precise treatment .In this study, we identified DEGs that are consistently expressed differentially in different cancers by performing differential gene expression analysis on transcriptomic data from TCGA and GTEx databases. A pan-cancer diagnostic model was further constructed to classify pan-cancers and normal samples with good performance. We also investigated the feasibility of using hub genes for prognostic assessment and drug sensitivity prediction. This study identified a set of candidate pan-cancer biomarkers, brought new insight into the etiology of tumors, and potentially provided new therapeutic targets for some cancers.https://gtexportal.org/home/) database to obtain the transcriptomic data of normal tissues. The related normalized mRNA data and clinical data were downloaded from the UCSC Xena database (https://xena.ucsc.edu/) and used for subsequent differential gene expression analysis.The transcriptome data of tumor samples and part of the matched control samples were obtained from the TCGA, including 9,213 tumor tissue samples and 723 para-cancerous tissue samples. In addition, we matched 7,008 tissue samples from GTEx  > 1.0. When readings for genes are not detected in half or more of the samples, these genes will be filtered out by quality control.The DEGs were identified using the DESeq2 R package (1.30.1). Genes were defined as differentially expressed by thresholds of adjusted p values of the statistical software R (version 4.0.4). p < 0.05 was considered to be statistically significant.Functional enrichment analysis based on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database  was perfhttps://string-db.org/) and visualized using Cytoscape software  (software . The tophttp://gepia2.cancer-pku.cn), which is a web server built for analyzing the RNA expression data of tumors and normal samples from the TCGA and the GTEx projects, using a standard processing pipeline. GEPIA2 was also used for generating survival heatmaps of hub genes.Patient survival and related analysis were performed on Gene Expression Profiling Interactive Analysis 2   with 20 up- and downregulated hub genes as input, respectively. GSCA is an integrated database for genomic and immunogenomic gene set cancer analysis, which predicts the drug response based on the calculated correlation between mRNA expression and drug IC50  were upregulated and 2 genes (PLIN4 and ADH1B) were downregulated in expression. In addition, four genes were differentially expressed in opposite directions among 28 tumors, ABCA9 was upregulated in LAML and down-regulated in the remaining 27 tumors, NPPA was upregulated in GBM and LGG and down-regulated in the remaining 26 tumors, while PBK and H2AC11 were down-regulated in TGCT and up-regulated in the rest 27 tumors.We further looked for shared DEGs that expressed differentially in most types of cancers. Among them, a total of 12 genes were found to be differentially expressed in all 28 tumors, of which 6 genes  is responsible for the condensation and stabilization of chromosomes during mitosis and meiosis  was thought to be associated with tumorigenesis, and its low proteomic levels were associated with poor prognosis in HCC patients, suggesting that CDC45 may be a novel prognostic marker for HCC  cells in vitro and in vivo and arrested cells in the G2/M phase of the cell cycle, which could be a novel therapeutic target for NSCLC . We replicated these hub genes as features for tumor and para-cancerous tissues classification using transcriptomic data from 14 additional datasets for different tumors, all with good accuracy and an AUC of at least 77.6%  curve illustrated the diagnostic ability and the area under the curve (AUC) showed the performance of a classification model. Based on the Lasso regression, the classifier performed excellently with an AUC value close to 89.4%  using thst 77.6% . These dst 77.6% .CDC45 plays a key role in DNA replication was significantly associated with survival in 9 tumors, and AURKB was significantly associated with survival in 8 tumors  will lead to differences in survival outcomes.Second, although our work suggests several biomarkers that may be useful for pan-cancer diagnosis and broad-spectrum anti-cancer drug selection, it should be noted that the present study is a retrospective study without validation in independent wet-lab laboratory experiments, and the limited sample size for some cancers could potentially lead to inaccurate or false-positive results. Besides, ICG expression was quantified at the transcriptomic level, while proteins such as mutation-derived neoantigens are the components directly involved in tumor immunity, and the protein expression does not exactly match the RNA expression , so the Third, we mainly explored the DEGs between tumor and para-cancerous tissues but did not address the discrepancies among different tumors. Future studies on specific markers for different tumors can be considered, which are expected to distinguish metastatic tumors that cannot be determined from the primary lesions and achieve early diagnosis and precision medicine for indistinguishable tumors.In summary, the hub genes identified in this study may serve as biomarkers to construct a pan-cancer diagnostic model that could effectively distinguish tumors from para-cancerous tissues and contribute to drug selection and development. Our findings provide new clues for pan-cancer classification in complex cancer biology and facilitate early diagnosis and precise treatment of cancer.


IntroductionWith the advent of fixed- and variable-loop suspensory fixation devices for arthroscopic anterior cruciate ligament (ACL) reconstruction, a maximum number of grafts can be placed within the femoral tunnel. Although several biomechanical studies have been conducted comparing these two devices, only a few comparative clinical studies are available. This study was conducted to compare the functional outcomes of arthroscopic ACL reconstruction using fixed-loop devices with those of variable-loop devices by determining their effect on graft laxity clinical assessment and patient-reported outcome scores.MethodologyOut of 32 patients  who underwent primary ACL reconstruction using tripled hamstring autograft, fixed- and variable-loop devices were used for 13 and 19 patients, respectively. Thirteen patients in each group were evaluated over a period of one year using the Lysholm knee score. Six patients in the variable-loop group had only six months of follow-up. Anterior drawer and Lachman tests were performed at six-month and one-year follow-ups, respectively.Resultsp<0.05). All the other parameters were comparable between the two groups. One patient in each group had ligament laxity at six-month and one-year follow-up, respectively.The mean ages of patients in the fixed- and variable-loop groups were 34.5ConclusionThis study showed no statistically significant difference in graft laxity or functional outcomes of arthroscopic ACL reconstruction with fixed- and variable-loop devices, except for a better patient-reported outcome score in the variable-loop group at six weeks of follow-up. Hence, there is a need for more comparative studies in this direction. This article was previously presented as a poster at the 64th Annual Conference of Indian Orthopaedic Association (IOACON 2019) on 22 November 2019 and as a scientific paper at the 44th State Conference of Karnataka Orthopaedic Association (KOACON 2020) on 1 February 2020.An anterior cruciate ligament (ACL) injury is the commonest knee injury seen by orthopaedic surgeons all over the world. Of all the factors contributing to a successful ACL reconstruction, graft fixation and tunnel incorporation are the most important determinants of post-operative knee stability .A short femoral tunnel effectively reduces the length of the graft in it, thereby compromising on strength of the graft-bone tunnel construct . ReducedIn fixed-loop systems, the length of the graft tunnel and the size of the loop have a significant impact on the outcome of ACL reconstruction. When the graft tunnel is short, closed-loop systems may not function effectively. A long loop may result in insufficient graft within the femoral tunnel.In variable-loop systems, pulling a series of sutures reduces the length of the loop and advances the graft to the femoral tunnel exit. This results in a larger contact area for bone-tendon healing, which in turn leads to better graft uptake. Hence, short tunnels do not preclude their usage. However, in biomechanical studies, these devices have exhibited more displacement than fixed-loop devices under lower loads than those occurring during early ACL rehabilitation . The relThe primary objective of this study was to compare the functional outcomes of arthroscopic ACL reconstruction using fixed-loop devices with that of variable-loop devices by determining their effect on clinically assessed graft laxity and functional outcome scores (the Lysholm knee score). The secondary objective was to evaluate the demographic distribution, mode, and MRI grading of ACL injuries and assess the pattern of associated injuries.This was a prospective study involving 32 patients with an ACL tear who visited the outpatient department and later underwent arthroscopic ACL reconstruction in the Orthopaedics Department of JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, between September 2017 and March 2019.The inclusion criteria were as follows: (1) age: 18 years or older; (2) no other illnesses preventing them from ambulating normally; (3) clinical and MRI proved ACL insufficiency of grades 3 and 4 ; (4) no The exclusion criteria were as follows: (1) ACL rupture associated with tibial or femoral condyle fractures and tibial spine avulsion fractures; (2) ACL reconstruction with other modes of fixation on the femoral side; (3) posterior cruciate ligament injury; (4) evidence of osteoarthritis on plain radiograph.Written informed consent for inclusion in the study was taken from all the patients. The treatment protocol was explained to them and they were briefed regarding their rights during the study. The treatment process had no adverse effects on the health of the participants, and the study was approved by the Institutional Ethical Committee of JSS Medical College, Mysuru .All the patients were subjected to detailed history taking and clinical examination. Lachman and anterior drawer tests were performed on all the patients before getting an MRI done. If MRI revealed significant femoral or tibial condyle contusion, surgery was delayed by three weeks. Functional limitations of all the patients were assessed preoperatively using the Lysholm knee scoring scale. Post-anaesthesia pivot shift test was done for further confirmation of ACL tear. All the surgeries were performed by an experienced team of orthopaedic surgeons trained in arthroscopy.Diagnostic arthroscopy was first done. Hamstring graft was then harvested, tripled, and pre-tensioned. The final graft size was 8 mm in all cases. The graft was then inserted through drill holes, assisted arthroscopically, and fixation was done with a fixed- or variable-loop device. The final femoral bone-tendon overlap length was 20 mm in all cases. The decision regarding the device to be used was made on-table based on the femoral tunnel length. If the tunnel length was less than 40 mm, variable-loop button fixation was done as a graft length of 20 mm had to be ensured within the tunnel (a 15-mm fixed-loop device is not available in our institute).o and full passive extension. Thereafter, progression to full knee flexion was encouraged by the end of six weeks. The active terminal extension was permitted only after six weeks. As and when patients demonstrated good quadriceps control, they were weaned off the brace and crutches. Patients were followed up at two weeks, four weeks, six weeks, three months, six months, nine months and 12 months. The objective and subjective evaluations were done with the Lysholm knee scoring scale. Graft laxity was assessed by a single individual, using Lachman and anterior drawer tests. These tests were performed on the affected as well as contralateral normal knees of patients, at six months and one year.After the surgery, all the patients underwent physiotherapy according to the institutional ACL rehabilitation protocol. Patients were encouraged to bear weight as tolerated with crutches and range of motion (ROM) knee brace locked in extension, second postoperative day onwards. In the first two weeks, emphasis was placed on patella mobilization, flexion up to 90t-test was used to compare the age distribution and knee ROM between the groups. The number of days after the injury at which the patients in both groups underwent surgery was compared using the Mann-Whitney U-test. A p-value of <0.05 was considered statistically significant for all tests.Data analysis was done using IBM SPSS Statistics for Windows, Version 21.0 . Chi-square analysis was used for comparing the sex distribution, mode of injury, MRI grading of an ACL tear, associated meniscal injuries, Lachman and anterior drawer tests for graft laxity at six months and one year and the Lysholm knee score grades of the two groups . An independent Of 32 patients  who underwent arthroscopic ACL reconstruction, the fixed-loop device was used in 13 patients and the variable-loop device in 19 patients. Six patients in the variable-loop group were lost to follow-up after six months. All the others were followed up over a period of one year. Baseline patient characteristics are mentioned in Table The distribution of patients with associated medial and lateral meniscus tears in each group is shown in Figure p=0.009) . Hagino et al. diagnosed an associated meniscal tear in 437 out of 552 knees with an ACL injury, on arthroscopic examination. The overall incidence of associated meniscal tear was thus found to be 79.2% [Lanzetti et al. noted Lysholm knee scores of 92.8 and 93.2 in the fixed- and variable-loop groups, respectively, at the end of 12 months [Wise et al. compared functional outcomes of the fixed- and variable-loop groups based on the Tegner scale and 12-Item Short-Form Health Survey, apart from the Lysholm questionnaire . Sharma The Lysholm knee score is one of the oldest knee-specific scoring systems used to assess patient-reported outcomes after ACL reconstruction . A studyWise et al. assessed graft laxity using a KT-1000 arthrometer. Clinical laxity of knees, as defined by KT-1000 >3 mm -18, was Apart from graft laxity, the only other complication encountered was knee stiffness. Persistent extensor lag was noticed at six months in one patient in the variable-loop group and incomplete flexion was observed in one patient each in both the groups. Knee stiffness could be because of improper tunnel placement or non-compliance with the rehabilitation protocol ,22. A tiLanzetti et al. found no difference in femoral tunnel enlargement on CT evaluation of knees in which ACL reconstruction was performed using fixed- and variable-loop constructs, 12 months after the surgery . Hoher eGraft healing is the most important factor influencing the outcome of ACL reconstruction. The factors influencing graft healing include the graft type, tunnel length and orientation, length of graft inside the tunnel, disparity between the diameters of the tunnel and the graft, graft tension, graft motion in the tunnel and type of fixation . We haveSeveral biomechanical studies have purported that variable-loop designs lengthen or slip, thereby delaying graft incorporation and causing knee instability ,28. PetrOur results were consistent with the findings of Boyle et al., who conducted a retrospective comparative study to ascertain whether adjustable-loop devices loosen after ACL reconstruction. They concluded that there was no statistically significant variation in the graft failure rate between fixed- and variable-loop designs up to two years post-ACL reconstruction .The fact that clinical studies like ours have not been demonstrating increased graft slippage in variable-loop designs as opposed to fixed-loop designs, as claimed by numerous biomechanical studies, could lead us to the fair assumption that biomechanical studies do not accurately represent clinical scenarios.Our study has a few limitations. Assessment of graft laxity might be biased due to the subjective nature of clinical assessment. Moreover, postoperative CT and MRI evaluations could not be done to assess the comparative femoral tunnel widening and the relative amount of graft in the femoral tunnel, respectively. Furthermore, the problem of relatively small sample size was compounded by the fact that six patients in the variable-loop group were lost to follow-up after six months.Our study showed no statistically significant difference in laxity of the graft or functional outcomes of arthroscopic ACL reconstruction with fixed- and variable-loop devices, except for a better patient-reported outcome score in the variable-loop group at six weeks of follow-up. Although many biomechanical studies have shown variable-loop designs to exhibit more displacement than fixed-loop designs, there was no significant difference in the displacement of the device between the two groups in our study. Hence, there is a need for more comparative clinical studies in this direction.


Coronavirus disease 2019 (COVID-19) is a viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The respiratory system is the main target of the virus; however, apart from lung disease, a relatively large proportion of patients develop thrombosis as well. We present the case of a 19-year-old male who was admitted after contracting community-acquired right-sided pneumonia. The patient had a history of COVID-19 infection four weeks before admission. The echocardiographic assessment revealed a 16 x 6-mm right ventricular (RV) thrombus. He underwent a cardiovascular magnetic resonance (CMR) study, which confirmed the findings. After ruling out the most common causes of hypercoagulability, COVID-19 was judged to be the cause of the thrombus. The patient was treated with warfarin. Follow-up imaging with echocardiography and CMR six months later revealed complete resolution of the thrombus. Hypercoagulability is a major complication of COVID-19 and in situ thrombosis can occur both in the arterial and venous circulation. The recognition of intracardiac thrombi even in low-risk patients with a history of COVID-19 infection and the immediate initiation of antithrombotic treatment to minimize the risk of embolization is of paramount importance. Advanced imaging techniques are often required to establish the diagnosis of this condition. Even though coronavirus disease 2019 (COVID-19) is primarily a respiratory disease, there is strong evidence to indicate the development of a prothrombotic environment leading to both arterial and venous thrombosis in many infected patients . RV appeared to have a normal size with preserved systolic function . Balanced steady-state free precession (bSSFP) cine images showed an oval-shaped mass of 16 x 6 mm within the cavity of the RV apex, with borders distinguishable from ventricular endothelium and trabeculations, raising the suspicion of an RV apical thrombus Figure . First-pA hypercoagulable workup including antiphospholipid antibodies, antinuclear antibodies, beta-2-glycoprotein, anticardiolipin antibody, homocysteine, antithrombin, protein C, and protein S was normal. The recent COVID-19 infection appeared to be the only plausible cause of the RV apical thrombus. LMWH was bridged to warfarin. The patient was successfully discharged within the next few days after achieving therapeutic levels of international normalized ratio (INR) between 2 and 3. Following the anticoagulation of the patient for six months, a follow-up TTE Figure  showed aFollowing the COVID-19 outbreak, a strong correlation between COVID-19 infection and hypercoagulopathy has been confirmed. This coagulopathy seems to be one of the most severe consequences of the disease. The COVID-19-related thrombosis as well as the abnormal coagulation parameters have been perceived as a poor prognostic marker in COVID-19 patients . Among tAn autopsy study of patients who died from COVID-19 showed a high incidence of deep venous thrombosis 58%) and fatal pulmonary embolism 33%) [3% [3]. S8% and faThe prophylactic administration of low-molecular heparin in all patients with COVID-19 infection is of paramount importance. Similarly, early diagnosis of thrombosis is vital, and TTE might be a reasonable option in most patients with a history of COVID-19 infection. TTE remains the main imaging technique for assessing the RV function, but since thrombus and myocardium may have similar echogenicity, TTE alone is sometimes not suitable to differentiate these two types of tissue. Whenever there is a high suspicion of RV thrombus or in cases of an inconclusive TTE and/or inconclusive transoesophageal echocardiogram (TOE), advanced imaging techniques like CMR could be employed as an additional modality to confirm the diagnosis.The superiority of CMR to detect thrombus in the RV with its higher sensitivity and specificity compared to the current standard with TTE and/or TOE has already been described in some case reports and case series ,9. BarbaIrrespective of the cause of RV thrombus formation, multimodality imaging, especially the use of CMR, despite its cost, offers a very useful additional diagnostic tool. CMR can be a supplemental tool besides TTE/TOE in the diagnosis and follow-up of incidental intracardiac masses in the RV. In our study, the TTE findings raised the suspicion of a thrombus. RV thrombus was diagnosed after the CMR during the analysis of all the obtained images, i.e., bSSFP cine sequences, FPP, and LGE sequences.Hypercoagulability is a major complication of COVID-19 and thrombosis can occur both in arterial and venous circulation including the RV. These thrombotic events appear to be most common in hospitalized COVID-19 patients, but our case showed that thrombotic events can be present in low-risk post-COVID-19 patients as well. The recognition of intracardiac thrombi even in low-risk patients with a history of COVID-19 infection, like our case, and the immediate initiation of antithrombotic treatment to minimize the risk of embolization, is crucial. The use of advanced imaging techniques like CMR can help in confirming the diagnosis.


Documented re-infection of COVID-19 is uncommon and doing a major spinal surgery in an elderly patient right after the recovery from the first event is itself a major undertaking. Re-infection after successful surgery points to the possibility of COVID-19 infection being a post-surgical complication. Here, we report a case of a 72-years-old elderly female who had presented to us with features of COVID-19 infection confirmed by reverse transcription polymerase chain reaction assay and unstable spinal fracture who underwent a pedicle screw fixation for the fracture of the third and fourth thoracic vertebrae after two consecutive negative serology assays. A month after discharge from the hospital, she presented with severe symptoms of COVID-19 again confirmed by two consecutive polymerase chain reaction assays. She was managed conservatively and was discharged without significant respiratory and neurological complications. We described this case in detail in addition to reviewing the pertinent literature. Being discharged home after successful surgery and coming back to the hospital with signs and symptoms suggestive of COVID-19 after a month of the previous infection is extremely rare.2 We report this unique case who was managed successfully in our hospital in addition to reviewing pertinent literature.Documented re-infection of COVID-19 is uncommon and is reported between 10-15%.A 72-year-old lady with a history of fall from a height of 3meters presented to the emergency department of our hospital in October 2020, with inability to move her left leg following the trauma. The patient also had shortness of breath for 4 hours and generalized chest pain at the time of presentation. She did not have fever, cough, sweating and palpitation. She was a hypertensive and was under regular medication (Telmisartan 40 mg once daily) for 8 years. She had no other significant past medical or surgical history. She had normal psychosocial history and had no prior history of identifiable genetic disorders within her family members. Her vitals were stable. On physical examination of the respiratory system, there was bilateral equal air entry with vesicular breath sounds and no added sounds. Neurological examination revealed paraparesis of 4/5 in her right leg and 3/5 in her left leg. The rest of the physical examination was normal. The family later disclosed that the patient had tested COVID-19 positive two days before the injury and was living in isolation in her home. Polymerase chain reaction (PCR) reports documenting the COVID-19 infection showed positive serological status (open reading frame (ORF)-1 ab gene Cycle Threshold (CT) value = 34.48 and Nucleocapsid gene (N-gene) CT value = 33.08). Patient underwent routine laboratory tests and imaging studies. A non-contrast computed tomography (CT) scan of the dorsal spine revealed a comminuted unstable fracture of the T3 and T4 vertebrae . There wThe patient was kept on bed rest in a thoracolumbosacral orthosis (TLSO) brace and received treatment for COVID-19 infection as per the government of Nepal protocol.Two weeks after the admission, the patient improved to normalcy and repeated PCR for COVID-19 was negative. She was operated successfully (long segment posterior instrumentation with pedicle screws) in November 2020 .The patient tolerated the surgery well. Three days after the surgery, she was mobilized in a wheelchair. Regular physiotherapy was provided and adequate dietary care was given to the patient. All events following the mobilization were satisfactory and the patient was discharged home 2 weeks after surgery.One week after the discharge, she presented to our emergency department again with chief complaints of shortness of breath, productive cough and generalized chest pain for 2 days. There was no history of fever, dizziness, sweating and palpitation. Her vitals were normal except respiratory rate which was 24 breaths per minute with O2 saturation of 69% in room air which increased to 94% at 6 litres per min of O2 via face mask). On general physical examination, the patient was ill-looking. She had bilateral wheeze with fine crepitations on lower lung zones. Her ECG was normal. Her laboratory investigations including D-dimer, RT PCR for possible COVID-19 re-infection and multidetector CT-scan of chest with a pulmonary angiogram were obtained. SARS CoV2 real-time RT PCR was positive . The chest CT scan revealed patchy consolidations with fibrotic bands in bilateral lower, right middle lobe, lingular and the apical- posterior segment of the left upper lobe . Mild plThe patient was managed conservatively in the COVID ward for a few days and discharged with advice to remain in isolation until she was disease-free. A repeat PCR done 3 weeks after discharge was negative. Currently (2 months after sugery), the patient is recovering well and is ambulatory . She doe3 COVID-19 imposes a unique risk to surgical patients. It has been reported that coronaviruses weaken the body's longterm response to the virus.4 As reinfections have been identified in patients with prior SARS-CoV-2 infections, the possibility of COVID-19 becoming a potential postoperative complication arises.5 Surgery in patients with COVID-19 infection increases perioperative complications.6 Hence, it is important to identify the serological status of the patients suspicious of the disease so that surgery can be safely planned. This ensures in the protection of patients and health care workers.6Surgery leads to the alteration of the immune response. Extent of surgery, age of the patient, health status before surgery, blood transfusion and medication intake are the factors that determine the immune response. Changes in the immune response may lead to the development of post-operative infections and affect the overall recovery of the patient.10 In patients with clinically mild COVID-19, the immunoglobulin G (IgG) and neutralizing antibodies are detected within 2 weeks and start to decline within 30 days of the symptom onset.10 Currently, it is unknown whether every infected patient mounts a protective immune response against the virus and how long any protective impact will last.11 In our case, the patient presented to our hospital with features of re-infection after 28 days. Although her SARS-CoV-2 antibodies were negative, we are unsure whether she specifically developed antibodies to the virus. But we were lucky to have the opportunity to intervene and make her spine stable so that she could be rehabilitated early.Our study was first of its kind reporting a successful major operation between 2 consecutive COVID-19 infection. Various studies have shown that the interval between re-infection and initial infection of COVID-19 is as short as 26 days.15 Our patient also had severe symptoms compared to her first documented infection.Studies have also shown increased symptom severity during the re-infection. Viral load, greater virulence and antibody-dependent enhancement are some major factors that define the severity of a re-infection.Our case points to the possibility of COVID-19 reinfection being a post-surgical complication. Our case highlights the fact that we should be aware of the possibility of re-infection in patients with COVID-19 infection.


The COVID-19 pandemic is likely to influence psychological health of pregnant and postpartum women.We conducted a non-concurrent cross-sectional study among 1145 women living in the Dutch-speaking part of Belgium, 541 pregnant and 604 postpartum women. We measured psychological health with the Whooley questions, Generalized Anxiety Disorder 2-item (GAD-2) and the Edinburgh Postnatal Depression Scale (EPDS) and compared the scores of pregnant and postpartum women before and during the COVID-19 pandemic.vs during the pandemic showed significant differences. Controlling for confounders, we observed a small main positive effect of having an infant during time of COVID-19 (F(1.13) = 5.06, p.025, d.27). The effect was significantly larger for women with (a history of) perinatal psychological problems (F(1.12) = 51.44, p < .001, d.82). Emotional support was significantly related to GAD-2 scores of postpartum women during the pandemic (F(1.90) = 35.54, p < .001). Postpartum women reported significant higher effects of the pandemic on their behavior compared to pregnant women (p.034).No differences were observed in the Whooley, GAD-2 or EPDS scores among pregnant women. The postpartum total GAD-2 scores before The COVID-19 pandemic seems to have a positive effect on postpartum women during the first year postpartum, in particular for women with (a history of) perinatal psychological problems and for those women who experienced emotional support. The findings suggest that less external stimuli caused by lockdown restrictions might have a positive effect on postpartum women’s emotional wellbeing. The sample consisted of white, educated women in a relationship and information regarding the extent of exposure to adverse COVID-19 consequences was lacking. We relied on self-selection and self-report. The postpartum pandemic sample was small. The 2019 novel corona SARS-nCoV-2-virus, better known as the Corona VIrus Disease (COVID-19), has become a threat to global health. The onset of COVID-19 was detected in Wuhan City, China in November 2019 and subsequently spread worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 disease as a global pandemic [Belgium introduced the lockdown period on March 13, 2020. The dominant message was to stay at home. Physical activities such as walking, or cycling were allowed and working from home was advised. Social distancing rules had to be respected, otherwise fines would follow. All catering establishments and non-essential shops were closed. Drones spreading announcements were used to remind people to stay indoors and warned people to adhere to the COVID-19 rules and to quarantine measures. People showed extreme hoarding behavior. Travelling abroad was prohibited and the borders with neighboring countries were closed. In May 2020 the lockdown eased; shops, bars and restaurants reopened, and people were allowed to meet up with more people. The first wave ended at the start of the summer holidays and swimming pools, gyms, cinemas, etc., were reopened and travelling within Europe was permitted. At the end of the summer 2020, the second COVID-19 wave hit Belgium, followed by a second lockdown on October 19, 2020. Working from home became mandatory. In December 2020 the regulations eased again and at the end of December 2020 the vaccination campaign kicked off, marking the end of Belgium’s second wave. In March 2021, the third wave hit Belgium although it showed a lower epidemic peak compared to the first two waves. During the pandemic waves, social distancing rules were synchronous with the rising and flattening curves of the waves, allowing meeting less or more people, depending on the number of positive tests and ICU admissions. Between March 2020 and April 2021 , 1116 pregnant Flemish mothers had a positive COVID-19 test of which 31 women were admitted on the Intensive Care Unit (ICU). Ten neonates of mothers with COVID-19 were tested positive. There were no maternal deaths as a result from COVID-19. .Domestic lockdown and social isolation have proven to be reasonably effective in terms of infection. However, on a psychosocial level isolation carries the risk for the onset of feelings such as uncertainty, fear, and despair as a result of isolation and of economical and job losses , 5. WorkWomen during the third trimester or women with underlying conditions might be at risk for critical respiratory illness and admission . ReportsFive main causes of psychological distress during lockdown have been identified: the duration of lockdown, fear of infection, feelings of frustration and boredom, inadequate supplies, and inadequate information , leadingBeing able to follow individuals based on common features such as region or country, background characteristics or socio-economic status and being exposed to the same pandemic regulations, classified according to exposure status  is of merit to make a statement whether emotional wellbeing of perinatal women changes during the pandemic , 32–34. © software).We conducted a non-concurrent cross-sectional study among women in Flanders (the Dutch-speaking part of Belgium) during any trimester of pregnancy and up to one-year postpartum. Eligible women were 18 years of age or older, with a good comprehension of the Dutch language. We excluded women with illnesses or life-threatening conditions requiring intensive medical support and mothers with children with congenital anomalies, severe pathology, or life-threatening diseases. The data were collected between August 8, 2019, and February 17, 2021, using online self-completed questionnaires  were informed about the study and were asked to spread flyers and posters announcing the study and inviting potential participants. The posters and flyers included a Uniform Resource Locator (URL) and Quick Response (QR)-code, anonymously redirecting to the questionnaire. Participants were also recruited via social media platforms, allowing snowballing.1 ‘no support at all’– 10 ‘a lot of support’). We added four COVID-19 related items enquiring about the effect of the pandemic on thoughts, emotional wellbeing, behavior, and physical health . The four COVID-19 items were each measured with one item using a 10-point scale . Mental health was self-reported with the Dutch versions of the Whooley questions [Three self-report mental health measures were completed alongside socio-demographic information and personal details. Emotional support and practical support of others were measured with one item with a 10-point scale  or negatively (no) . A positThe participants who responded positively to the Whooley questions, completed the GAD-2. The GAD-2 is a short version of the seven-item scale, detecting the core symptoms of generalized anxiety in primary care settings. The GAD-2 questions refer to feelings of anxiety over the last two weeks . ResponsThe EPDS is a ten-item questionnaire to screen for the likelihood of antenatal and postnatal depression, referring to feelings and thoughts during the past seven days. Responses are scored from 0–3 with a total score range from 0–30 . In thisvs unexposed women). Significant differences in GAD-2 and/or EPDS scores were followed by a univariate analysis of covariance, to determine whether being pregnant or having a child younger than one year old during a time of COVID-19 regulation produces a significant difference against antenatal and postpartum women before the pandemic started, controlling for differences in sample characteristics. The Kruskal Wallis test was used to examine the differences of the COVID-19 related items’ scores between pandemic pregnant and postpartum women. The p-value was set at < .05. An a priori sample size calculation showed that we needed a minimum of 382 participants for both pregnant and postpartum samples  to make inferences from the sample. The analyses were performed using the Statistical Package for the Social Sciences© (SPSS) version 27.First, the cases in the period 3 February–13 March 2020 were deleted. This period was regarded as a transition period between the officially announced start of the pandemic and the first lockdown in Belgium, likely to confound the true effect of the COVID-19 regulations. We split the cases in pre-COVID-19  and during COVID-19  groups. Normality of distribution was checked with the Shapiro-Wilk test. When fewer than 10% of the value for a case or for an item were missing, values were imputed with sample means. We calculated descriptive statistics for the sociodemographic and personal characteristics. We summed the scores of the GAD-2 and EPDS and established the cases with scores above cut off values. The strategy for model building was as follows: Mann-Whitney U test and chi-square tests were used to calculate differences between background characteristics and Whooley, GAD-2 and EPDS scores between the study samples . The questionnaire included a privacy note explaining confidentiality, anonymity, data handling and dissemination of the results. Participants were informed about the study and when they agreed to participate, they provided a written consent. All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki).p .006; p < .001). Our analysis of maternal perinatal psychological health included 1145 EPDS scores, 1145 Whooley-items and 719 GAD-2 scores.We received 1701 questionnaires of which 266 were removed due to incomplete socio-demographic details and missing values on all the three psychometric scales. Of the remaining 1435, we deleted 290 cases that had completed the questionnaire between February 3 and March 13, 2020 see . The remp < .001). The unexposed postpartum group had significantly more often a history of psychological problems or (a history of) perinatal psychological problems then the exposed group . The exposed postpartum women reported significantly higher levels of emotional support, compared to the pre-COVID-19 unexposed participants (p .007)  see .We analyzed the Whooley-items and the EPDS scores of 541 pregnant women. The participants who responded positively to one or two of the Whooley-items, completed the GAD-2 (n = 318). We analyzed the Whooley-items and the EPDS scores of 604 postpartum women. The participants who responded positively to one or two of the Whooley-items, completed the GAD-2 (n = 401). F(1.39) = 5.06, p .03). The squared deviation of the postpartum GAD-2 mean scores was 0.87. We performed a univariate analysis with the GAD-2 total scores as the dependent variable and time period  as our fixed-factor. Levene’s test was not significant (F(1.39) = 1.46, p .23). We added (a history of) psychological problems in general and perinatal psychological problems as random factors and length of postpartum period and emotional support as covariates. There were no outliers or multicollinearity between factors and covariates. We observed a small main positive effect of having a child during time of COVID-19 (F(1.13) = .5.06, p .025, d .27), indicating that GAD-2 scores among postpartum women were significantly higher before  than during the pandemic . We observed a large positive effect of the COVID-19 among postpartum women with (a history of) perinatal psychological problems during the pandemic  (F(1.12) = 51.44, p < .001, d .82). We did not observe a significant effect among women with (a history of) non-perinatal related psychological problems. The covariate emotional support was significantly related to the GAD-2 scores of postpartum women before or during the pandemic (F(1.90) = 35.54, p < .001). No significant relationship was observed with length of postnatal period, suggesting that GAD-2 scores were not significantly different between women who had recently given birth or a longer time ago during the first year postpartum. Kruskal Wallis showed that the pandemic had a significant higher effect on the behavior of postpartum women when compared to pregnant women (p .034) but not on their thoughts (p .25), emotions (p .45) or on their physical health (p .49).As shown in The COVID-19 pandemic has been conceived as a major risk factor for depressive and anxiety symptoms for pregnant and postpartum women , 35. BecThere are several possible explanations for the differences in psychological health in postpartum psychological health of postpartum women before and during the pandemic. Firstly, we observed a significant difference in the postpartum period at point of completing the questionnaire between the pre-COVID-19 group and the postpartum women during the pandemic. The women during the pandemic had given birth more recently compared to the pre-pandemic participants, implying that the women that completed the questionnaire during the pandemic had been pregnant during the pandemic. Because of little or inconsistent available information about risks for pregnant women, these postpartum women might have been so relieved that their baby was healthy, positively affecting their levels of anxiety. During the social isolation period of the COVID-19 pandemic, it might be that women received more support from their partner. In our study this applied to emotional support. Due to restrict visiting, social distancing rules and other regulations affecting daily activities, out of the house activities and going out or having visitors, women were less disturbed by external stimuli compared to the pre-COVID-19 women—providing the opportunity having more time to focus on (a life with) a baby, facilitating maternal-child attachment. It is known that a maternal-child attachment buffers postpartum symptom of anxiety pandemic . Our finOur study shows strengths and limitations. This study adds to the existing reports about the mental health response of pregnant and postpartum women during COVID-19 pandemic and to make a comparison with women during pre-COVID-19. This study provided the opportunity to compare the prevalence of anxiety and depressive symptoms before and after the national declaration of the COVID-19 pandemic, with similarity in restrictions compared to other countries , 32–36. The antenatal and postpartum period are particularly vulnerable times for women. Even for healthy women, a pregnancy can be overwhelming and may lead to new symptoms of anxiety—especially during a pandemic. This study overall reports no significant effect of the COVID-19 pandemic on depression and anxiety of pregnant women when compared to pre-pandemic women, which seems reassuring in terms of overall perinatal mental health during COVID-19. The restrictions associated with the COVID-19 pandemic even seem to have a positive effect on psychological health of postpartum women, on anxiety and even more specifically for women with a history of perinatal psychological problems. Emotional support has a mediating effect on postpartum psychological health. Postpartum women reported a behavioral change during COVID-19, suggesting that lockdown restrictions might have a positive effect on postpartum women’s emotional wellbeing. More studies should be done to shed more light on psychological health of pregnant and postpartum during the COVID-19 pandemic. For future studies it would of merit to incorporate larger perinatal subsamples of exposed and unexposed COVID-19 women, to assess the extent to exposure of adverse COVID-19 consequences and to consider the postpartum time point of measure.


To support proactive care during the coronavirus pandemic, a digital COVID-19 symptom tracker was deployed in Greater Manchester (UK) care homes. This study aimed to understand what factors were associated with the post-uptake use of the tracker and whether the tracker had any effects in controlling the spread of COVID-19.Daily data on COVID-19, tracker uptake and use, and other key indicators such as staffing levels, the number of staff self-isolating, availability of personal protective equipment, bed occupancy levels, and any problems in accepting new residents were analysed for 547 care homes across Greater Manchester for the period April 2020 to April 2021. Differences in tracker use across local authorities, types of care homes, and over time were assessed using correlated effects logistic regressions. Differences in numbers of COVID-19 cases in homes adopting versus not adopting the tracker were compared via event design difference-in-difference estimations.Homes adopting the tracker used it on 44% of days post-adoption. Use decreased by 88% after one year of uptake . Use was highest in the locality initiating the project . Care homes owned by a chain had lower use , and use was not associated with COVID-19 or staffing levels. Tracker uptake had no impact on controlling COVID-19 spread. Staff self-isolating and local area COVID-19 cases were positively associated with lagged COVID-19 spread in care homes .The use of the COVID-19 symptom tracker in care homes was not maintained except in Locality 1 and did not appear to reduce the COVID-19 spread. COVID-19 cases in care homes were mainly driven by care home local-area COVID-19 cases and infections among the staff members. Digital deterioration trackers should be co-produced with care home staff, and local authorities should provide long-term support in their adoption and use.The online version contains supplementary material available at 10.1186/s12879-022-07939-6. Residents of care homes  are particularly vulnerable to developing severe illness from COVID-19 , 3. By tWith the emergent threat of COVID-19, a digital tracker was introduced into Greater Manchester (GM) care homes to facilitate proactive management of COVID-19 and residents’ health . The tra2The tracker allowed staff to input residents’ COVID-19-related symptoms  and local NHS community response teams with the hypothesis that this would result in swift measures being put in place . Aggregated home-level daily data were visible to area hubs, GPs, and Greater Manchester health and care providers via a visual GM dashboard held by Greater Manchester Health and Social Care Partnership (GMHSCP). This provided a longitudinal dataset of COVID-19 cases and residents’ well-being which included: an interactive map using circles of different colours and sizes to display homes with and without COVID-19 cases, the latest assessment date, daily assessed and reported residents, and a summary dashboard showing trends in COVID-19 and residents’ well-being.The tracker was deployed in GM, England from April 2020 onward. The deployment was initiated as a partnership between Health Innovation Manchester (HInM), GMHSCP, and a local authority and its NHS Foundation Trust . By the Like many digital technologies deployed worldwide to fight COVID-19 , the traThe continuous use and success of such digital trackers depend on a multitude of factors –9. TrackThe evidence published to date on the use and effectiveness of digital technologies to fight COVID-19 has mostly focused on national-level experiences, comparing the use of big data, artificial intelligence, cloud computing, 5G, etc., for remote health services, communication, tracking, and monitoring in the fight against COVID-19 . In adulThere is limited quantitative evidence on the sustained use of digital trackers, and factors affecting use, for COVID-19 management in adult social care or the impacts such trackers may have on containing the pandemic spread. Particularly, literature on the abandonment of digital innovations versus sustained use is sparse in adult social care . Address3Was there any association between the care home use of a digital COVID-19 tracker and the type of care home, time since tracker adoption, frequency of COVID-19 cases, care home staffing levels, supplies of PPE, and the care home location?Did the uptake and use of a COVID-19 tracker impact on the number of COVID-19 cases in care homes?This study aimed to enhance the literature by assessing post-uptake actual use of a digital tracker and whether there was any association between tracker uptake and use and the spread of COVID-19 in care homes in Greater Manchester, UK by answering the following questions: This study evaluates the use and impact of a digital tracker for COVID-19 management in care homes in Greater Manchester (GM), UK. It is reported according to the STROBE framework .Tracker deployment started in one GM locality in April 2020. Care homes in a second locality began using the tracker in July-August 2020 and by the end of 2020, care homes from eight (of 10) GM localities were using the tracker. In total, 91 GM care homes adopted the tracker at different times during 2020, the number reached 139 by April 2021.The study considered all 547 care homes in the GM database across the 10 GM localities. The analysis of tracker use covered the 139 homes that adopted the tracker over the period April 2020 to April 2021. For the tracker impact evaluation, data from year 2021 were excluded due to possible differential effects of COVID-19 vaccination. 13 care homes were dropped from the analysis due to a lack of data on COVID-19 cases. Impact evaluation analysis thus included 534 care homes for the April to December 2020 period.The study was a prospective cohort analysis of care homes’ use of the tracker and COVID-19 cases in the care homes. Daily data on the number of residents whose health was assessed and reported in the tracker were used to develop a measure of tracker use. These data were obtained via the GM health and care system for the 139 homes that adopted the tracker over the study period. Daily data on care home staffing levels, staff-self-isolating, occupancy levels, number of available beds, residents with COVID-19 (either positive or having symptoms), a flag about whether the home accepts new admissions  and PPE supplies were provided by the GM health and care system via COVID-19 dashboards for all GM care homes  by type of home and across localities . Fixed eCorrelated random effects logistic regression estimated odds of COVID-19 outbreaks (where an outbreak is defined as having at least one COVID-19 positive resident or resident having symptoms on a given day in a care home) by home residential status, ownership type, CQC quality ratings, and type of residents served. For methods and a discussion of missing data see Additional file To assess the impact of the tracker on COVID-19 spread, an event design difference-in-difference (DID) model was estimated . This coSummary statistics of the number of homes and their key characteristics are provided in Table Figure  Regression analysis explored variations in tracker use by locality and types of homes  compared with small homes [1–23 occupied beds] and care homes with residents who had learning disabilities and/or autism  compared with care home with no such residents. On the other hand, care homes CQC rated as requiring improvement and care homes owned by a chain had higher odds of COVID-19 outbreaks . Not-for-profit care homes and homes with dementia users experienced more outbreaks and residential only care homes fewer outbreaks but the difference became insignificant after controlling for staff, home local area cases, and PPE. This means that the differences in the odds of COVID-19 outbreaks in these latter care homes were mediated by differences in their staff, home local area cases or PPE supplies.Several parametric and non-parametric DID estimations were run to assess the impact of the tracker on COVID-19 cases among care residents. No statistically significant difference was found in the number of COVID-19 cases between the care homes that did and did not adopt the tracker. The unadjusted and adjusted estimation results for the standard DID are given in Table  Our analyses identified several other factors that were consistently associated with the number of COVID-19 cases in care homes . However, this result does not hold in the additional sensitivity analyses in the Additional file The onset of COVID-19 led to a host of digital innovations to fight the pandemic. Digital technology has played a key role alongside physical restrictions in containing the virus, and in the provision of online health and other social-economic services , 11. LitThis study contributes to the existing knowledge by analysing the use of a digital COVID-19 tracker over time and space, the factors associated with use and its impact on the spread of COVID-19. The study found that among the 139 care homes that adopted the tracker, its use decreased by more than 75% within one year of deployment. Tracker use was 30 times higher in care homes in the locality where the tracker was developed and tested. Tracker use was 66% lower in care homes owned and run by chains than in individually owned homes. Moreover, tracker use was negatively associated with care home PPE supplies and was not associated with COVID-19 rates or staffing levels.The study analysed whether the odds of experiencing COVID-19 outbreaks were associated with any specific care home characteristics. The findings suggested that the odds of experiencing COVID-19 outbreaks were higher in care homes owned by a chain (odds of the outbreak were twice compared with single-ownership care homes) and homes rated as requiring improvement. The odds of experiencing COVID-19 outbreaks were 80% lower in care homes with residents with learning disabilities and/or autism.The final part of the study analysed whether the tracker had any impact on rates of COVID-19 in care homes and found no difference in the rates of COVID-19 according to whether homes adopted the tracker or not. The two main drivers of the rates of COVID-19 in care homes appeared to be COVID-19 cases in the local area and amongst the care home staff. A staff member self-isolating on a given day was associated with a 29% increase in COVID-19 cases among the care residents seven days later. The findings that digital symptom tracking had no impact on containing COVID-19 spread in care homes, and that workers and home surroundings were key drivers of COVID-19 spread into care homes, are also confirmed in other studies –29.The finding that the odds of tracker use were higher in Locality 1 than the reference Locality 7 and that the percentage of residents receiving daily assessments was also relatively stable overtime (Fig.  The pressure the COVID-19 pandemic placed on adult social care was one reason for lower uptake and use of the tracker as recognised in the parallel implementation study . NeverthThe finding that the tracker was ineffective in controlling COVID-19 spread in care homes is plausible for two reasons. Firstly, it has been shown that 50 to 70% of care home residents with COVID-19 were asymptomatic , 29, so This study has several strengths. The study is particularly novel in its assessment of tracker use, enabling an assessment of use over time since adoption that adjusted for a range of potential confounding factors. The impact assessment also adjusted for a range of potential mediating factors with consistent findings across a range of sensitivity analyses. Secondly, our analyses examined COVID-19 spread in care homes within a region with its own devolved health and care system . The locHowever, this was an observational study and has limitations. The study used a combination of COVID symptoms data and confirmed cases of COVID from the GM COVID-19 situation report instead of confirmed COVID cases only for the impact evaluation. These have both merits and weaknesses. To use confirmed cases data, one must know the testing regimes of homes as low/high COVID-19 cases among homes might be the reflection of differences in testing regimes. Conversely data based on symptoms will miss asymptomatic residents and potentially misclassify people has having COVID-19 when they have symptoms due to other illnesses. Whilst symptoms may not necessarily represent confirmed COVID-19 cases, we found a close association between our COVID-19 data and COVID-19 related deaths in care homes (see the Additional file The data used for the COVID-19 impact evaluation of the tracker were an unbalanced panel as some care homes started data submission at later stages of the study period. Unbalanced panels always raise the possibility of selection bias. Our inspection of data revealed that care homes from different local authorities started submission at different calendar dates. Thus, it is unlikely that any unobserved care home characteristic was the reason for the data being an unbalanced panel. Similarly, the initial uptake of the tracker was largely decided by local authorities. Nevertheless, the descriptive statistics revealed that care homes that adopted the tracker were larger on average, raising the possibility of selection into the tracker. To account for the possible selection bias, the sensitivity analyses matched the care homes on different CQC characteristics before the estimation of tracker impact. Despite all these, the study finding of no causal association between tracker uptake and COVID-19 spread should be taken with caution.The study also analysed the association of staff infections and local area COVID-19 cases with COVID-19 spread in care homes. COVID-19 cases in care home residents might come from COVID-19 infections among the care home staff and local area COVID-19 cases and vice versa. However, exploring both possibilities were not the focus of this study. The current study only explored the relationship between infection of a member of care home staff and resident COVID-19 cases seven days later.Our study suggests several potential areas for future exploration. First, though, the tracker was ineffective in controlling the virus spread, such trackers might have impacted on the number of residents admitted to hospital and/or COVID-19-related deaths through active information sharing and responses from the local health systems. One possible area of investigation might be the impact of such trackers on excess deaths in care homes. Similarly, the tracker might have impacted the quality of residents’ care or had workforce implications. The digital skills the adult social care workforce developed during the pandemic might have enhanced their capabilities and motivation to co-produce and evaluate digital solutions for online consultations, falls prevention, and early signs of deterioration. Finally, the relationship between homes owned by a chain, tracker use, and COVID-19 outbreaks needs further study to understand the mechanisms behind this, as similar findings emerged from a study in Canada as well .This study demonstrated that the post-uptake use of a digital tracker deployed in GM care homes during COVID-19 was short-lived except in a local authority that was a partner in its initial development and deployment and has a relatively well-integrated health and social care system. COVID-19 cases in care homes were mainly driven by care home local-area COVID-19 cases and infections among the staff members, and the digital symptom tracking was not helping in containing COVID-19 spread in care homes.COVID-19 has driven the development and adoption of new digital technologies at scale and speed. During COVID-19 the focus was on the uptake of digital technologies and removing barriers to uptake. The learning from the initiatives during COVID-19 may be used to identify practices that can be put in place for creating a supportive environment for sustained and effective use of digital technologies. The findings from this study imply that strong local leadership and co-production might be key success factors in the sustained use of digital technologies in adult social care. Similarly, the integration of primary, secondary, and social care systems are identified as enablers in increasing engagement with digital technologies . Clear eAdditional file 1: Appendix S1. Explains the dataset. Appendix S2. Discusses the estimation methods and sensitivity analysis tables of the tracker use. Appendix S3. Outlines the estimation method selection for estimating the odds of COVID-19 outbreaks. Appendix S4. Contains details of estimation methods and sensitivity analysis tables for the tracker impact on COVID-19 spread.


This study investigated the effect of different curing conditions on the degree of conversion and mechanical properties of contemporary dual-curing resin cements. The material specimens were either light-cured directly, light-cured through a 1-mm lithium disilicate glass-ceramic layer, or self-cured. The degree of conversion was measured in 0.1-mm films using Fourier-transform infrared spectroscopy 1 day, 7 days, and 28 days post-cure. Specimens used to study the flexural strength and modulus were prepared according to the ISO 4049 protocol, stored for 28 days post-cure, and subjected to accelerated aging by absolute ethanol immersion. The degree of conversion values ranged between 44.3–77.8%. Flexural strength varied between 11.4–111.1 MPa, while flexural modulus amounted to 0.7–5.5 GPa. The degree of conversion was significantly affected by material type, curing conditions, and post-cure time; however, variations in curing conditions were the least influential factor. A statistically significant effect of curing conditions on the degree of conversion was identified for only one of the five materials tested, whereas the flexural strength and modulus of all tested materials were significantly reduced in the experimental groups that were light-cured through a ceramic layer or self-cured. The effect size analysis showed that mechanical properties were most affected by the material type, while the differences in curing conditions were less influential. A comparison of the degree of conversion and mechanical properties indicated that different curing conditions may lead to significantly different flexural strength and modulus, which are not necessarily accompanied by identifiable variations in the degree of conversion. Resin-based cements are widely used nowadays for luting various indirect dental restorations. The basic composition of these materials is similar to that of restorative methacrylate-based, glass-filled resin composites, albeit with some adjustments which are necessary to achieve the required viscosity for thin-layer application, adhesion-promoting compounds (silanes and 10-methacryloyloxydecyl dihydrogen phosphate) and various combinations of self-cure and photo-cure initiators  . RecogniIn addition to mechanical properties, which represent macroscopic material behavior, a more fundamental parameter used to quantify the extent of polymerization in methacrylate resin-based materials is the degree of conversion (DC), defined as the fraction of C=C double bonds that have been converted into single bonds . BesidesThe DC values and the post-cure DC development over 28 days would not be affected by the curing conditions ;The mechanical properties measured after 28 days would not be affected by the curing conditions.The null hypotheses were as follows:This study investigated four dual-cure resin cements, with one light-cure resin cement as a reference. Compositional details of resin cements, as provided by the respective manufacturers, are presented in 2 for 20 s by positioning the curing unit light guide tip immediately adjacent to the cement specimen;LC-dir (Light-cured directly): 1080 mW/cm2 for 20 s due to interposition of a 1-mm layer of lithium disilicate glass-ceramic  between the curing unit light guide tip and the cement specimen;LC-cer (Light-cured through a ceramic layer): 280 mW/cmSC (Self-cured): without light illumination.To evaluate the effects of different radiant exposures, cement specimens were cured using the following three protocols (except for the light-cure cement which was cured only using the first two protocols):Light-curing in the LC-dir and LC-cer protocols was performed using a third-generation wide-range LED curing unit Bluephase PowerCure . The radiant exitances specified above were measured using a National Institute of Standards and Technology (NIST)-referenced and calibrated spectrometer MARC .n = 8) were prepared and left to age under dry conditions in a laboratory incubator at 37 °C for the following time points: 1 day, 7 days, and 28 days.Thin discs of resin cement  were prepared by placing cements between two polyethylene terephthalate (PET) foils  with microscope cover slides as spacers. Gentle pressure (200 g) was applied on the upper PET foil to standardize specimen thickness. The specimens were then cured using one of the above-described curing protocols. To evaluate the development of DC as a function of time, three separate subsets of specimens  were recorded for DC calculation. These spectra were recorded within 20 s after extruding the uncured cement onto the ATR crystal in order to prevent artificially reduced concentrations of double C=C bonds due to self-curing. DC was calculated from the change in peak heights of the spectral band at 1638 cm−1  in the cured and uncured specimens. Since the commonly used spectral band at 1608 cm−1 (aromatic C⋯C) was missing in some cements, the spectral band at 1600 cm−1 (C-H stretching) was selected as an internal reference used to normalize FTIR spectra. The DC was calculated according to the following equation: After being stored for a particular time, the specimens were withdrawn from the incubator and used for DC measurements employing attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). The specimen surface opposite to that exposed to the curing unit tip was pressed against the diamond ATR accessory of the FTIR spectrometer . FTIR spectra were collected in absorbance mode, using 30 scans and a spectral resolution of 4 cm3) were prepared according to the modified ISO/DIN 4049:1998 protocol. The specimen length and inter-support span (16 mm/12 mm) were shorter compared to the most recent ISO 4049:2019 protocol (25 mm/20 mm) as the former protocol results in a smaller volume of material under load, which was considered more clinically relevant [n = 20). Mechanical testing was performed in a universal testing machine  using an inter-support span of 12 mm and a crosshead speed of 0.5 mm/min according to NIST 4877 guidelines. Specimens were immersed in distilled water at room temperature during the testing procedure. Flexural strength (FS) and flexural modulus (FM) were calculated according to the following equations:fF = force at fracture (N), l = inter-support span (mm), b = specimen width (mm), h = specimen height (mm), lF = force at the end of the linear part of the force-deflection diagram (N), and ly = deflection at the end of the linear part of the force-deflection diagram (mm).The specimens for the three-point bending test  at an overall significance level of 0.05.The assumption of a normal distribution of data was verified using Shapiro-Wilk’s test and the inspection of normal Q-Q diagrams. The FS and FM data were analyzed using a three-way ANOVA with factors “material”, “curing protocol”, and “post-cure time”, whereas for the comparison of the DC data, a two-way ANOVA with factors “material” and “curing protocol” was used. Since statistically significant results of the Statistically significant effects of the factors “material” and “curing protocol” and their interaction were also identified for FS and FM, as shown in The DC values shown in The mechanical properties in This study evaluated the effect of different curing protocols on the DC and mechanical properties of contemporary dual-curing resin cements. To evaluate the post-cure DC development, measurements were performed after 1, 7, and 28 days. Since DC increased significantly during the 28-day observation period, the specimens for FS and FM evaluation were given 28 days to complete the post-cure polymerization before being immersed in ethanol as a means of accelerated aging. A statistically significant effect of curing protocols on DC was identified for only one of the five materials tested (Panavia V5). In contrast to these results, the mechanical properties of all tested materials were significantly reduced in the experimental groups that were light-cured through a ceramic layer or self-cured. Hence, the first null hypothesis was rejected only for Panavia V5, while the second null hypothesis was rejected for all tested materials.Dual-curing cements are characterized by two simultaneously occurring modes for initiating free radical-mediated dimethacrylate polymerization. The light-curing mode is intended for rapid on-demand setting, while the self-curing mode is intended to compensate for the lack of light exposure at sites that are covered by opaque portions of the indirect restoration and hence inaccessible to illumination . Both cuSignificantly better DC attained by direct light-curing compared to curing through ceramics or self-curing was identified only for Panavia V5 after 1 day and 7 days, but the differences leveled off after 28 days and became statistically similar for all curing protocols. The manufacturer’s information for Panavia V5 indicates that this material does not contain the usual amine co-initiator in order to improve the color stability of the material. Since the chemical composition of the co-initiator that replaced amine has not been disclosed by the manufacturer, we could not speculate whether it is a possible cause for the different polymerization behavior of Panavia V5 compared to the other materials tested. A possible reason for the lack of statistically significant effects of curing conditions on DC in four out of five tested materials could also be the high scatter of data in some experimental groups (coefficients of variability ranging from 2.0–17.3%), which is due to the use of thin films sensitive to polymerization inhibition by atmospheric oxygen .The slow development of DC over a certain post-cure period is a well-known phenomenon in dimethacrylate-based dental resin composites, explained by the immobilization of reactive species within the polymerizing network . Most ofConsidering the very different extents of post-cure DC increase among the materials tested, it should be noted that the DC values reached within 24 h, which are evaluated in the vast majority of studies on dual-curing cements ,19,20,21−1 is assumed, without calibration using external references. Since there is no guarantee of the linearity of this relationship, which is likely to be affected by the composition of individual materials, small inter-material differences in DC do not necessarily mean that one material has better conversion than another. On the other hand, differences among DC values attained by different curing modes within a single material are more meaningful because the comparisons within a material exclude the possible influence of material composition.DC values obtained by vibrational spectroscopy have been reported to vary due to differences in methodology, specimen preparation, and material composition , which pFor a given resin cement, the variations of DC are the main determinant of the material mechanical properties of the material, i.e., higher conversion is generally associated with better mechanical properties ,45. HoweThe observed differences in mechanical properties seem surprising considering that the DC data after 28 days showed no significant differences among curing protocols. However, these pronounced differences among curing modes can be explained by the aggressive accelerated aging protocol (7-day immersion in absolute ethanol). This type of accelerated aging is capable of highlighting subtle differences in network structure and is therefore commonly used to indirectly quantify crosslink density in methacrylate resin-based composites . EthanolThe specimens used for the mechanical tests were artificially aged by immersion in water and ethanol, as the properties of composite materials are known to degrade when exposed to an aqueous medium . Since tISO 4049 prescribes a minimum FS of 50 MPa for luting materials. Due to the aggressive artificial aging used in our study, our results should not be directly compared to these reference values. However, the fact that some of the tested resin cements  maintained their FS above the ISO 4049 threshold despite being subjected to aggressive aging suggests that these materials would likely meet the prescribed value of 50 MPa even if subjected to much less aggressive aging as prescribed in the ISO 4049 protocol, i.e., one day in distilled water at body temperature.Heterogeneity of mechanical properties, as observed in the present study, also occurs in clinical scenarios, because when complex indirect restorations are cemented using dual-cure resin cements, the curing light is considerably attenuated or completely blocked at some sites. Hence, different gradients of mechanical properties occur at the interface between the restoration and the dental hard tissues. These gradients may not be as pronounced as the differences resulting from an aggressive accelerated aging protocol in this study, or they may take some time to develop as the material ages.The 28-day development of DC and the response to different curing conditions proved to be highly material-dependent. Most of the investigated cements showed a significant post-cure DC increase, whereas variations in curing conditions were less influential for the final DC values. The comparison of DC and mechanical properties showed that different curing conditions may lead to significantly different FS and FM, which are not necessarily accompanied by different DC values. Direct light-curing led to the highest FS and FM values, suggesting that the investigated dual-cure cements should be optimally light-cured in order to maximize mechanical properties.