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Introduction: Urine drug testing has been the standard for monitoring opioid compliance in chronic pain patients. The COVID-19 pandemic created a dilemma for opioid monitoring by severely limiting in-person testing due to safety concerns. Oral fluid toxicology emerged as a feasible, alternative test due to its ability for remote sample collection under virtual supervision while minimizing infringements on patient privacy. However, the efficacy of these two tests for reliably detecting opioids should be explored prior to transitioning to testing only with oral fluids. Method(s): In this study, we compared morphine levels in oral fluid and urine toxicology studies from 5 randomly selected patients from a Chronic Pain Center who were regularly taking high doses (>=90 mEq) of extended-release morphine. Charts from the start of the COVID-19 pandemic until July 2022 were reviewed for urine and oral fluid testing results and medication regimens. All oral fluid and urine test results and collection methods were validated by a nationally recognized toxicology lab. Prescription Monitoring Program (PMP) reports were reviewed for each patient to observe pre-testing prescription trends. Result(s): We found that the overwhelming majority of patients had at least 1 false negative oral fluid test result. The remainder of the oral fluid results were below threshold (10 ng/mL) or ranged from 11.3 to 54 ng/mL of morphine. 80% of patients (n = 5) had at least one negative or positive-but-below-threshold (10 ng/mL) result in their oral fluid sample analyses. In contrast, none of the urine studies had negative results. Urine studies for all patients were positive for morphine and well-above primary cutoff values (100 ng/mL) with levels >6000 ng/mL. PMP reports did not reveal any aberrant drug taking behavior in any of the patients. No unprescribed medications or illicit substances were detected in any of the oral or urine samples. Conclusion(s): The prevalence of false negative results for the detection of morphine metabolites in oral fluid toxicology may be higher than clinicians are currently aware of. Physicians and other providers monitoring opioid compliance in chronic pain patients should keep this possibility in mind when selecting toxicology tests and making conclusions about aberrant drug-taking behavior. Larger scale studies are needed to compare oral fluid and urine levels of morphine with extension to other commonly prescribed opioids. Disclosure: Evan Chung, MD: None, Joseph Valenza, MD: NoneCopyright © 2023
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Intro: The COVID-19 pandemic is caused by the SARS-CoV-2 virus, an enveloped RNA of the coronavirus family. The advancement in molecular technology and biochemistry has accelerated the development of diagnostic reagents and assays. Much attention has been focused on the S protein, but the high mutation rate in this region could lead to false negative results. Thus, a better target protein for diagnostic application is needed for accurate detection. Method(s): Nucleotide sequences encoded for membrane (M) glycoprotein gene region of SARS-CoV-2 from Malaysian isolates were extracted from GISAID, aligned, and selected accordingly. The DNA plasmid was commercially synthesized with codon optimization for Escherichia coli (E. coli), and the presence of the M gene was confirmed by PCR. The plasmid was then transformed into E. coli. Later, the expression of M glycoprotein was induced, separated on an SDS-PAGE gel, and transferred onto a nitrocellulose membrane, followed by immunostaining. Finding(s): The analysis of the M glycoprotein against the Omicron strains demonstrated that the amino acid is conserved (99.5%). The M glycoprotein was successfully expressed and detected with antibodies from SARS-CoV-2 infected patients at ~26 kDa. The protein is currently upscale for the generation of monoclonal Ab (Mab). Discussion(s): The M protein of SARS-CoV-2 is more conserved among the virus and also has been reported to confer antigenic properties. Selection of M protein perhaps a better option compared to current detection assays that use spike (S) protein, which could lead to false negative results, as this gene region particularly the ribosome-binding domain (RBD) rapidly undergoes mutations. The utilization of M protein potentially improves negative predictive value (NPV) of the diagnostic test. Conclusion(s): Further development of diagnostic reagents is needed to improve the assay's specificity. The newly developed M protein and the MAb can be used to generate a more accurate viral detection assay.Copyright © 2023
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Federated learning is the process of developing machine learning models over datasets distributed across data centers such as hospitals, clinical research labs, and mobile devices while preventing data leakage. This survey examines previous research and studies on federated learning in the healthcare sector across a range of use cases and applications. Our survey shows what challenges, methods, and applications a practitioner should be aware of in the topic of federated learning. This paper aims to lay out existing research and list the possibilities of federated learning for healthcare industries.© 2022 Copyright held by the owner/author(s).
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Background: Respiratory cultures are an important part of clinical care for people with cystic fibrosis (CF). Telemedicine visits during the COVID-19 pandemic have not allowed for routine collection. To address this, the University of Michigan Adult Cystic Fibrosis Program mailed home culture kits to patients. We hypothesized that results from home sputum samples would be consistent with prior cultures obtained in sputum collected in clinic but that self-collected throat swabs would provide false-negative results. We also sought to determine percentage return rate. Method(s): Adults with CF were sent culture kits containing a specimen cup and a throat swab. Patients had the choice to submit either sample for processing. Medical personnel provided written instructions with the culture kits and, on occasion, instructed patients on proper collection techniques via phone. Samples were then refrigerated for up to 24 hours before a delivery service returned the specimen to a University of Michigan laboratory for analysis. Data collected from December 2020 to December 2021 (N = 77) included percentage return rate, result, source, and presence of microorganisms. Pairwise culture data of samples collected in clinic versus home-collected samples within 1 yearwere included in the analysis. Descriptive statistics and Cohen kappa correlation coefficients were computed for all culture data and subgroups (Table 1A-E). Result(s): Of 77 culture kits returned, 46 had corresponding clinic samples collected using the same method, and the remaining 21 were collected using different methods (throat swab vs sputum sample). Overall, approximately 200 kits were mailed to patients, with a return rate of 38.5%. A similar percentage of positive culture results was obtained with same method of collection: sputum and throat samples (Table 1C, D, E), although the discordance rate between cultures collected in clinic and at home ranged from approximately 10% to 30%. Correlation between clinic and home culture data was generally good throughout, except for clinic Table 1 ( 115): Analysis of respiratory culture results for (A) all cultures, (B) different collection, and (C, D, E) same collection method. *p < 0.05. Cohen kappa correlation coefficient between groups: poor agreement <0.20;fair agreement = 0.21-0.40;moderate agreement = 0.41-0.60;good agreement = 0.61-0.80;very good agreement = 0.81-1.00. PsA = Pseudomonas aeruginosa;Staph = Staphylococcus aureus.(Table Presented)versus home throat swabs, probably because of a lowevent rate in the small sample size. Conclusion(s): The data suggest that, overall, clinic and home culture kits provide similar positive results, although discordance in specific culture results was common. This may be due to natural fluctuations from culture to culture in people with CF. A limitation of this study is that the cultures being compared in our study were not completed on the same day. Nevertheless, our data also indicate that collection technique may influence results for certain microorganisms. How these differences might influence antibiotic selection and treatment outcomes in the era of telemedicine requires more investigation. The return rate was found to be relatively low, demonstrating the need for interventions to improve patient outreach and compliance.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Background: Remote rhythm monitoring with wearable devices is increasingly used especially for early detection of atrial fibrillation/flutter (AF/Afl), being the access to hospital discouraged, especially for frail elderly patients, due to the burden and risk of COVID-19 pandemic. Whereas devices using photo plethysmography (PPG) may misinterpret as AF pulse irregularities due to extrasystoles, patient-directed recording of a single (usually wrist-to-wrist) lead ECG (LEAD I) with hand-held devices or smartwatches have been developed to increase accuracy in AF detection. However, although recent studies validating such devices single-lead ECG recording have shown high sensitivity and specificity, false negative findings such as those reported here are still possible and must be prevented [1]. Purpose(s): Given previous experience of diagnostic uncertainty or failure of the smartwatch ECG (SW-ECG) LEAD I to detect AF/Afl, we have tested if false negative diagnosis could be avoided by recording in addition at least one right precordial (pseudo-V1) lead analyzed by a trained healthcare professional. Method(s): Over one calendar year observation, five patients with previous history of ablated supraventricular arrhythmias suffering sudden palpitations suspected of paroxysmal AF/Afl were instructed to record with their smartwatch at least one precordial lead in addition to LEAD I, to monitor ECG until the termination of symptoms. The SW-ECG strips were sent by telephone for professional interpretation. Diagnostic accuracy based on LEAD I and pseudo-V1 were independently validated by two cardiologists (diagnostic goldstandard - DGS). Result(s): 22 AF/Afl events occurred. Pharmacological cardioversion to sinus rhythm (SR) was obtained in 64%. 192 ECG strips were transmitted. 43,7% of the strips were automatically classified as not significant (or not valid ). Compared to DGS, out of 108 valid strips, correct automatic identification of AF/Afl was obtained in 36,4% with LEAD I, in 33,3% with pseudo V1 and in 54,5% with combined leads, respectively. Interestingly, the SW algorithm has wrongly diagnosed as SR, not only LEAD I, but also 39,4% of pseudo-V1 strips, despite clear-cut evidence of typical flutter waves (Figure 1), when RR intervals were regular due to high degree (e.g., 4:1) A-V block. Conclusion(s): With simple instructions, patients (or their relatives) can easily record an additional precordial (pseudo-V1) SW-ECG lead, that may enhance sensitivity and specificity for remote detection of AF/Afl. However, at present, visual interpretation of SW-ECG by a trained healthcare professional is still needed to guarantee 100% correct diagnosis of AF/Afl, crucial to reduce thromboembolic risk and timely initiate the appropriate treatments. The automatic interpretation of SW's ECG could be improved by appropriate training of a machine learning approach to detect and analyze the atrial waveform provided by an additional pseudo-V1 lead.
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Background: COVID-19 is associated with the development of life-threatening prothrombotic events, including pulmonary emboli (PE), for which the gold standard investigation is a CTPA. Aim(s): To assess the incidence of PE in our local high-dependency and ward-based COVID-19 ward and identify common indications for CTPA. Method(s): Data was collected retrospectively from inpatients admitted to our COVID-19 ward between August 1st to October 31st, 2021. Patient demographics, D-dimer values, oxygen requirements, and CTPA request indications and findings were analysed. Result(s): From a total of N=123 patients, N=45 (36.9%) had a CTPA, and N=4 (3.3% of all patients, 8.9% of CTPA requests) were positive for PE. N=44 (97.8%) CTPAs were requested to rule out a PE, with the main indications being a raised D-dimer (26.7%), hypotension (24.4%), persistent oxygen requirement (22.2%), and desaturation (22.2%). N=18 (40%) required non-invasive ventilation (NIV) at the time of CTPA request. The median time spent on therapeutic anticoagulation before a CTPA was 6 days (IQR 9). N=8 (17.7%) had bleeding complications from therapeutic anticoagulation. Conclusion(s): Our 3.3% incidence of PE is lower than the 11.7% average in a recent meta-analysis of ITU patients, consistent with studies showing that those with more severe COVID-19 have a higher incidence of PE (Tan, B.K. et al. Thorax 2021;76: 970-979). Our study was limited, as our patients could not have a CTPA whilst on NIV. They remained on therapeutic anticoagulation during this time, leading to potential false-negative results. Further studies are needed to estimate the incidence of PE and optimum duration of thromboprophylaxis in non-severe COVID-19 cases.
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The outbreak of coronavirus disease 2019 (COVID-19) affects the world. It is highly contagious and spreads quickly. COVID-19 severely increases the medical burden and interferes with our normal work. This article introduces our experience on treat oral cancer patients during the epidemic. The negative impact can be minimized through reasonable and orderly arrangement.Copyright © 2021 The Authors
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To date, an adequate and timely assessment of the number of cases is the basis of effective measures aimed at preventing the spread of COVID-19 infection. Real-time reverse transcription polymerase chain reaction (RT-PCR) remains the gold standard for confirming COVID-19. The purpose of the work: to analyze the experience of the city virological center of the S.P. Botkin Clinical Infectious Diseases Hospital (Botkin Hospital) for the examination for the presence of SARS-CoV-2 coronavirus by PCR in the period from 2020 to 2022. Materials and methods. The systematization of PCR studies on COVID-19 for the period 2020-2022 was carried out. A total of 221,901 people were examined, positive results were obtained in 55,372 (24.95%). Among the contingents of the examined patients, patients who underwent inpatient treatment at the Botkin Hospital, Conclusions. This study analyzed the possible causes of false-positive and false-negative PCR results. The correlation of the number of positive results with the dynamics of detection of new cases of COVID-19 in St. Petersburg during the 2020-2022 pandemic is shown. It has been established that the proportion of patients examined more than 3 times during the period of hospitalization remains significant. This fact requires the closest attention, given the high cost and laboriousness of PCR studies.Copyright © 2022 Authors. All rights reserved.
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The ongoing COVID-19 pandemic reminded once again that microbiological diagnostic methods are irreplaceable in both diagnosing and detecting asymptomatic persons. At present, real-time reverse transcriptase polymerase chain reaction (RT-PCR) is the gold standard method for diagnosing COVID-19, but the test's accuracy varies in sample quality. Especially in the last stages of the disease, negative results of nasopharyngeal or oropharyngeal swab samples or rapid antigen tests do not necessarily mean that these patients do not carry the virus. Considering that a significant number of COVID-19 patients need intensive care and mechanical ventilation in the late period, which sample should be taken from where and when should be evaluated. Lower respiratory tract samples have a more significant chance of finding viral RNA than upper respiratory tract samples. Technical recommendations and the virological diagnostic methodologies and used in the intensive care unit of patients infected with SARS-CoV-2 are summarized in this article. We aimed to emphasize the need to get a sample from the right place at the right time for a reliable virological diagnosis.Copyright © 2022 by The Cardiovascular Thoracic Anaesthesia and Intensive Care.
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Objectives: Early investments in new diagnostic technologies that allow for rapid and decentralized testing were critical in reducing SARS-CoV-2's detrimental health and economic effects. This study evaluates public knowledge about, acceptance of and willingness to use COVID-19 self-testing kits. Methods: An online descriptive cross-sectional questionnaire was used in this study. The final study population included all contacted national and resident adults, age 18 and over, who were willing to engage in the study. The survey was divided according to participants' demographic information and 11 questions assessed the respondents' understanding of and willingness to use COVID-19 self-testing kits. The statistical analysis was carried out using SPSS version 24. Multivariate linear regression models were used to identify the factors influencing respondents' knowledge of and attitudes toward the acceptability of self-testing kits for COVID-19 and their willingness to use these kits. Key findings: A total of 876 respondents participated in the study and completed the whole questionnaire. The average knowledge score on the acceptability of and willingness to use self-testing kits for COVID-19 was 70.2%, with a 95% confidence interval (CI) [69.1%, 71.4%]. Participants who were postgraduate, female and vaccinated against COVID-19, as well as employees and older participants, were jointly highly associated with higher levels of knowledge about, acceptance of and willingness to use self-testing kits for COVID-19. Moreover, participants who had been infected with COVID-19, were vaccinated against COVID-19 or were female, employees, older, Western or Arabic were jointly highly associated with positive attitudes about the acceptability of and willingness to use self-testing kits for COVID-19. Conclusions: The majority of the respondents have acceptable levels of knowledge about, acceptance of and willingness to use self-testing kits for COVID-19. Nonetheless, future studies should consider the issues of pre- and post-test counselling, false negative results and the sale of unregulated testing kits. Additional information should be communicated so that people can make informed decisions and be protected from possible abuse of COVID-19 self-testing kits when they become available in pharmacies.
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Corona Virus Disease (Covid-19) is a label species of the Corona virus family. It can cause a variety of illnesses, from the ordinary cold to advanced respiratory syndromes like Middle-East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). This virus is highly contagious and spreads due to the droplets produced by coughing and sneezing. Though there are several ways to prevent the transmission of Covid-19, one of the most important and effective way is using a face mask or a face shield. In this paper, we constructed face mask detection framework using Viola-Jones algorithm in order to recognize whether an individual is wearing a mask or not. This algorithm includes the selection of Haar features of a face, integral image creation, adaptive boost training and cascading. An extensive study is carried out in order to analyze the performance of the proposed approach;we use a large facial image dataset from the publicly available MAFA dataset. The results indicate the proposed method can accurately identify face mask wearing images with a classifier accuracy of 98.26%, suggesting it might be useful in Covid-19 prevention. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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Introduction: On January 2021 the Department of Psychiatry became the only unit exclusively dedicated to COVID patients with severe mental illness in acute decompensation. Only patients in risk of rapid medical deterioration were excluded and forwarded to intensive care. Objective(s): Discussion of this unprecedented experience. Method(s): Analysis of 28 patients hospitalized during 3 months with both an acute psychiatric disorder and an SARS-CoV-2 infection;description of the multidisciplinary intervention made. Result(s): Our samplewas characterized by a majority of patients with an acute psychotic episode derived from a schizophrenia spectrum disorder (42%) or a bipolar affective disorder (21%). Only 3% of the patients had a diagnosis of severe major depressive disorder. And 10% of patients developed severe respiratory symptoms requiring oxygen or urgent transfer to COVID medical wards. Most patients presented periods of psychomotor agitation, lack of impulse control and self-aggression. Psychopharmacological and psychotherapeutic interventions had to be adapted to these unusual conditions. Most of them had already gone through a period of isolation in the buffer ward created to exclude false negatives, which promoted atypical deliriums and symptoms of post-traumatic stress. The psychiatric team was faced with the emergent need to adapt an intervention model based on trust to a model that had to prioritize physical safety. Conclusion(s): The pandemic experience was transformative forall who lived through it. From the challenge perspective, it may have been enriching. But the maintained confrontation with the antithesis of therapy, defined by "caring, supporting, communicating, approaching", was devastating in ways that we consider essential to be debated.
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Background: Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) is a rare, anti-platelet factor 4 (PF4) antibody-mediated prothrombotic syndrome associated with the AstraZeneca (AZ) Covid-19 vaccination. Diagnostic criteria include thrombosis, thrombocytopenia, appropriate timing post AZ vaccine, and demonstration of an anti-PF4 antibody by enzyme-linked (Table Presented) immunosorbent assay (ELISA). ELISA methods have varying sensitivity and specificity for detecting anti-PF4 antibodies, therefore, functional assays (modified serotonin release and flow cytometry) assist in diagnosis. In Australia, the primary assay for detection of anti-PF4 antibodies is the Asserachrom HPIA IgG ELISA. Aim(s): To assess the accuracy of an alternate ELISA method for suspected VITT compared to the gold standard (clinicopathological diagnosis). Method(s): 96 stored frozen samples from patients with suspected VITT, previously analysed by Asserachrom HPIA IgG ELISA (Stago, Melbourne, Australia), were tested using the Hyphen Biomed Zymutest HIA IgG ELISA (Haematex Research, Sydney, Australia). These patients had confirmed thrombosis within 42 days post first dose of AZ vaccine. Cases were classified as 'serologically confirmed VITT' if clinicopathological criteria were met, and initial ELISA testing and/or functional assays were positive. Results were interpreted as positive or negative for anti-PF4 antibodies using the manufacturer's cut-offs derived for the diagnosis of Heparin-Induced Thrombocytopenia. Result(s): 96 patient samples were tested, including 35 classified as VITT (Table 1). The Hyphen assay had a moderate sensitivity (82%), including 2 probable false negatives on initial testing which were strongly positive by Hyphen assay. The specificity was 93%, including 5 probable false positives on initial ELISA which were negative by Hyphen assay (Table 2). Conclusion(s): The Hyphen ELISA is suitably accurate for the diagnosis of VITT. These data highlight the limitations of using a single ELISA testing method for anti-PF4 antibody detection. In cases with high clinical suspicion, a second ELISA method or functional assay should be considered.
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Background: Accurate detection of SARS-CoV-2 (SCoV2) variants of concern (VOCs) is pivotal as they affect transmission, monoclonal antibody therapy and escape from natural and vaccine-induced immunity. Aim: We developed nucleic acid testing (NAT) for dual detection of SCoV2 wildtype and mutant sequences of the spike gene (Del69/70, L452R, E484A, E484K, N501Y) defining specific VOCs (Basel- SCoV2-WT/MUT). Methods: The retrospective study cohort (n = 77) consisted of SCoV2 wildtype and Alpha, Beta, Gamma, Delta and Omicron VOCs as defined by whole genome sequencing (WGS). The prospective study cohort (N = 249) consisted of locally circulating Omicron BA.1, BA.2 and BA.5 variants. Both cohorts were also analyzed using a commercially available test (Roche cobas®-SCoV2-variant assay). Results: Basel-SCoV2-WT/MUT accurately identified all VOCs in the retrospective study cohort. SCoV2 RNA copy numbers <1'000 copies/ mL decreased the efficacy of the Basel-SCoV2-WT/MUT NAT. At these low SCoV2 RNA levels, the cobas®-SCoV2-variant assay showed partial or full drop-outs leading to false-negative results. In the prospective study cohort, Basel-SCoV2-WT/MUT accurately identified Omicron BA.1, BA.2 and BA.5 variants by detecting Del69/70 mutant and wildtype sequences, including four patients with WGS confirmed co-infection undetected by the cobas®- SCoV2-variant assay. Conclusion: In conclusion, Basel-SCoV2-WT/MUT is accurate and allows rapid and low-cost detection and differentiation of SCoV2 VOCs. Importantly, the assay can be readily adapted to new spike mutations as new SCoV2 variants emerge.
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Introduction: Following assessment of the effectiveness and feasibility based on the results from a two-year population-based nationwide prospective multi-center trial, the Korean government implemented a national lung cancer screening program using low-dose computed tomography (LDCT) for high-risk smokers in 2019. Methods: National Health Insurance Corporation selected high risk targets who are current smokers aged 54 to 74 years with 30 packs per year or more smoking history on the basis of national health-screening database. (Figure 1). Those eligible were offered lung cancer screening by invitation letters in every two years. Screening units provide LDCT using radiation less than 3mGy by at least 16-row multi-detector CT scanners. Screening results were reported by Lung Imaging Reporting and Data System (Lung-RADS). The examinee received results by mail or e-mail;after then, counseling on results and mandatory smoking cessation counselling were provided by certified doctors. National Cancer Center monitored participation rates, post-counseling rates and statistics of screening result for quality control. Screening positive rate is defined as proportion of Lung-RADS category 3 and 4 nodules. Results: The participation rate gradually increased from 24.8% among 332,244 eligible targets in 2019, 25.9% in 2020, to 38.7% among 310,260 targets in 2021, however, the proportion of examinees who participated in post-counseling decreased from 46.3% in 2019 to 32.7% in 2021 due to the COVID-19 pandemic (Figure 2). The positive rates slightly decreased from 9.2% in 2019 to 8.7% in 2021. The variation in positive rates of screening units showed a tendency to decrease (in 2019, the 1st quartile was 4.3%, and the 3rd quartile was 12.9%;and in 2021, 5.2% and 12.5% respectively). Conclusions: National lung cancer screening program has been implemented successfully in Korea with controlling screening positive rates not so high. Controlling false negatives and strengthening post-screening management including smoking cessation counselling needs to improve. [Formula presented] [Formula presented] Keywords: National Lung Cancer Screening, Quality control
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Background: Pediatric Infammatory Multisystem Syndrome Associated With SARS-CoV-2 (PIMS) is a new insidious disease which in several points may mimic Kawasaki disease. Patients diagnosed with one of the aforementioned conditions are initially treated with intravenous immunoglobulin (IVIG). However, up to 20% of children diagnosed with Kawasaki disease appear to be resistant to such therapy. Similarly, substantial portion of PIMS patients requires second line treatment including systemic glucocorticoids. There are several calculative models, including the Kobayashi Score, which are utilized to predict patients' response to such treatment. To our best knowledge, the scoring systems derived from Kawasaki disease have not yet been assessed whether they can fulfl similar role in PIMS patients. Objectives: There were two essential questions to be addressed in the study: (1) Can the Kobayashi Score be utilized in making clinical decisions regarding concomitant treatment in PIMS patients? (2) Is there any modifcation that may increase the accuracy of the original score? Methods: First step of the study involved 19 patients diagnosed with PIMS between July 2020 and June 2021. The statistical analysis including each parameter of the Kobayashi Score has been performed in order to determine potential alterations of the score. Then, the numerous variants of modifed score have been compared in terms of their positive and negative predictive values in order to determine new PIMS IVIG Resistance Score (PIRS). In the next phase of the study, both scores have been validated in the second cohort involving 16 patients diagnosed with PIMS between July and December 2021. The fnal assessment has been performed in the unifed study group (35 PIMS patients). Results: The Kobayashi Score (see Table 1) signifcantly differentiated PIMS patients in terms of good response or resistance to IVIG (p=0.03967). However, the score returned a few false positive (3 out of 9) and false negative (2 out of 10) results. After step-by-step verifcation of clinical and laboratory parameters, authors developed a tentative PIRS (see Table 1) including the following criteria: hyponatremia, days of fever and platelet count (derived from the Kobayashi Score but with different cut-off levels) supplemented with procalcitonin level and percentage of lymphocytes. In the validatory phase of the study, both scores had equal accuracy to predict treatment response. The analysis of receiver operating characteristic curve in the unifed study group has shown better performance of PIRS (Youden index 0,72) than the Kobayashi Score (Youden index 0,49). Conclusion: The Kobayashi Score is worth being considered to estimate the risk of resistance to IVIG in PIMS patients. Nonetheless, it is not free from false positive and false negative results. The postulated modifed score called PIRS can become a promising alternative but it requires further validation in larger cohorts of patients.
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Introduction Previously our group had identified 20 features which were associated with the development of upper gastrointestinal (UGI) cancers using a machine learning approach.[1] We sought to refine this model and to validate this in an independent dataset to assess its generalisability in an interim analysis. Methods We selected patients who were recruited for the multicentre Saliva to Predict rIsk of disease using Transcriptomics and epigenetics (SPIT) study to develop our model. Patients were recruited from 2-week wait suspected UGI pathways and additionally enriched with patients with confirmed oesophageal adenocarcinoma admitted as inpatients. We used regularised logistic regression (glmnet) from the caret package in R software to create the model. 60% of the data with 10-fold cross validation was used for training, with the remaining 40% for testing. For validation, we used data from the predicting RIsk of disease uSing detailed Questionnaires (RISQ) study, an ongoing prospective multicentre study using the questionnaire based on the our previous work.1 We evaluated the model using area under the receiver operating characteristic curve (AUC). Results We included 93 cancer and 715 non-cancer patients for training and testing and 21 cancer and 203 non-cancer patients for validation. We further reduced the model to 18 features without significant detriment to model performance. In the training and testing data AUC was 0.86 (95%CI: 0.81- 0.91) and 0.75 (95%CI: 0.67-0.83) respectively. We set a threshold of 0.03 as a cut off based on a cost function where false negatives had a 50-time greater impact than false positive cases (figure 1). For the validation cohort we achieved an AUC of 0.95 (95%CI: 0.90-1.00). This equated to a sensitivity 0.952 and a specificity of 0.897 for detecting cancer. Conclusions Initial results from our model compare favourably with the Edinburgh Dysphagia Scale, which has a sensitivity and specificity of 0.984 and 0.093 respectively.2 It also appears to have a high specificity, potentially helping to reduce unnecessary endoscopies. We aim to further increase the size of the validation cohort to ensure its robustness and generalisability. Our model could be applied to triaging and prioritising endoscopic referral backlogs as a result of COVID- 19.3.
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Background: CNS involvement in CLL is rare and it usually occurs in late-stage CLL disease. There is usual delay in the diagnosis due to its variable manifestations, challenging diagnosis process and possible misdiagnosis with a mimicker condition. I am sharing our relative successful experience with this challenging case that had satisfied outcome after going through comprehensive investigations and treatment journey treating his symptoms until arriving the final diagnosis and getting the best treatment option. Material(s) and Method(s): A 42 years old male, with recent COVID-19 infection, presented with multiple progressive neurologic symptoms over one month;started as numbness around the mouth, reduced facial sensation and a feeling of band like sensation below the costal margins. On exam, he had left abduction restriction, diplopia on left gaze and upbeat nystagmus, reduced facial sensation and hyperesthesia. The reflexes were 1+ in the upper limbs, 3+ in the lower limbs, up going planters, tingling from the feet up to T6 level and postural tremor bilaterally. His CSF showed high protein level. MRI brain/ spine revealed left frontal juxtacortical white matter and bilateral middle cerebral peduncles lesions with post-contrast enhancement and long segment spinal cord demyelinating plaques. He was initially treated as a case of Acute disseminated encephalomyelitis (ADEM) post viral infection in a background of CLL. The delayed diagnosis was due to temporal relation of neurological manifestation to viral infection, similar MRI lesions to ADEM and multiple negative CSF results of cytology and flow cytometry. He had persistent disabling symptoms and enhancing lesions in MRI despite being treated with IVMP, IVIG and PLEX. He was managed for ADEM based on responsiveness to the recommended therapy step by step. Firstly, he received a high-dose corticosteroids, secondly IV immunoglobulin but he was still progressing and considered as steroid-unresponsive ADEM. lastly, plasma exchange was done when he exhibited progressive symptoms with fair improvement. Interestingly, the patient showed significant improvement in the clinical and radiological parameters after starting him with a new anti-leukemia medication (Acalabrutinib) for his concurrent active condition. He run out of his medication for around 1 week and he experienced recurrent of the neurological manifestation and the previous lesions in the images. A repeated flow cytometry for the third time came positive for CLL cells and the final diagnosis of CNS involvement by CLL was established. The diagnosis was made after the exclusion of other etiologies. Result(s): The patient received Ibrutinib at a standard dose and as a monotherapy. It is an efficient chemotherapy that crosses the blood brain barrier and has showed a favorable clinical, biological and radiological outcome. The patient is back to his work and his daily activities have improved. Conclusion(s): In case of inconclusive work up, CSF analysis should be repeated testing for cytology and flow cytometry\immunophenotypes as the false negative results are common. Our patient had an active CLL proved in his investigations, and the fact that the patient responded very well to the new chemotherapy should alert the diagnosis of CNS involvement by CLL and directs towards repeating investigations and introducing aggressive treatment strategy to target both hematological and neurological complications of the condition.