Staging of COVID-19 disease, using selected laboratory profiles for predictionprevention and management of severe SARS-CoV-2 infection in Africa-review

There are many uncertainties on the future management of the coronavirus disease 19 (COVID-19) in Africa. By July 2021, Africa had lagged behind the rest of the world in Covid-19 vaccines uptake, accounting for just 1.6% of doses administered globally. During that time COVID 19 was causing an average death rate of 2.6% in Africa, surpassing the then global average of 2.2%. There were no clear therapeutic guidelines, yet inappropriate and unnecessary treatments may have led to unwanted adverse events such as worsening of hyperglycemia and precipitating of ketoacidosis in administration of steroid therapy. in order to provide evidence-based policy guidelines, we examined peer-reviewed published articles in PubMed on COVID 19, or up-to date data, we focused our search on publications from 1st May 2020 to 15th July, 2021. For each of the studies, we extracted data on pathophysiology, selected clinical chemistry and immunological tests, clinical staging and treatment. Our review reports a gross unmet need for vaccination, inadequate laboratory capacity for immunological tests and the assessment of individual immune status, clinical staging and prediction of disease severity. We recommend selected laboratory tools in the assessment of individual immune status, prediction of disease severity and determination of the exact timing for suitable therapy, especially in individuals with co-morbidities.Copyright © 2023 Sendagire H et al.

Kikuchi-Fujimoto disease type lymph node reaction with increased plasmacytoid dendritic cells may appear as a side effect following COVID-19 vaccination: Report of a case and literature review

Subsequent to mass vaccination programs against COVID-19, diverse side effects have been described, both at the injection site, such as pain, redness and swelling, and systemic effects such as fatigue, headache, muscle or joint pain. On rare occasions, a lymphadenopathic syndrome may develop, raising the clinical suspicion of a lymphoproliferative disorder. We present the case of a 30-year-old woman who developed self-limiting left axillary lymphadenopathy following COVID-19 vaccination. To date, only seven similar cases with a complete clinicopathological description have been published, and fourteen cases have been notified to the European adverse events databases (Eudravigilance) in relationship with vaccination against COVID-19. It is important to be aware of this potential complication when a lymphadenopathic syndrome develops following vaccination, to avoid unnecessary treatment.Copyright © 2023 Sociedad Espanola de Anatomia Patologica

Increase of high flow nasal cannulas use after the pandemic in bronchiolitis: a more severe disease or a changed physician's attitude?

In the 2020-2021 winter season, COVID related measures reduced the incidence of bronchiolitis to a tenth. The aim of this study was to describe the chat-up of hospitalization for bronchiolitis during the latter winter. The primary outcome was the prevalence of high flow nasal cannula (HFNC) that spread over the pre-pandemic decade. We performed a retrospective study at four Italian hospitals collecting data on infants (<1 year) hospitalized for bronchiolitis from September 1st to March 31st. During the last winter, 197 out of 300 patients (66%) received HFNC treatment;5 patients out of 22 (23%) during the pandemic winter(p<0.001);99 out of 259 (38%) and 102 out of 295 (35%) in the latter two pre-pandemic winters (p<0.001). Non-invasive ventilation and continuous positive airway pressure use similarly increased: 68 patients (23%) in the last winter vs 2 (9%) in the pandemic winter;42 (16%) and 36 (12%) in the latter two pre-pandemic winters (p=0.003). Intensive care admission increased to 29% from 22-15% of the pre-pandemic period. HFNC use was extended this winter to 2.8+/- 2.7 days vs 1.7+/- 2.7 and 1.3 +/- 2.2 in the two pre-pandemic SOPswinters respectively (p<0.001). On the opposite, all the other severity indexes such as intubation need, in-hospital length of stay or ICU length of stay did not differ. Therefore a more severe disease course behind the respiratory support choice seem unlikely and we rather recognize a change in paediatrician attitude to less tolerate respiratory distress with an easier step-up in respiratory support leading to an overtreatment starting with a non-evidence-based and maybe non wisely choice of HFNC candidates.

Tools to Reduce Low-Value Care: Lessons From COVID-19 Pandemic Comment on "Key Factors that Promote Low-Value Care: Views of Experts From the United States, Canada, and the Netherlands".

Based on a summary of interviews with 18 experts, Verkerk et al defined the seven key factors that promoted low-value care, which included system, social, and knowledge factors. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, these key factors have been influential due to the uncertainty of the disease at the beginning of the pandemic. Globally, several measures have been implemented to reduce low-value care practices and promote high-value care for COVID-19 patients. From huge multicenter, non-industry sponsored or multiplatform trials, to the use of social networks sites is an indispensable and effective way to disseminate medical information. Thanks to these measures, we have transformed a scenario of ignorance into an evidence-based medical scenario in less than a year. Verkerk and colleagues' proposed key factors are an excellent framework for characterizing and highlighting the lessons that can be learnt from how we have fought against the pandemic and low-value practices.

LOOK BEFORE YOU LEAP: A REPORT OF A MISSED DIAGNOSIS

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Tuberculosis (TB) rates in the USA are currently at the lowest in history. During 2010-17, only 5175 TB cases occurred in children in the USA. Even in Hidalgo County on the Texas-Mexico border there were only 36 cases of TB among all age groups in 2020. CASE PRESENTATION: An asymptomatic 3-year-old male presented to the PICU with a positive PPD and an infiltrate in the right lower lobe on chest x-ray. Once three morning gastric aspirates were obtained child was started on a 4 drug regimen recommended by the health department, and sent to the pulmonology clinic for further care awaiting identification and sensitivity of an organism. Child was born at 35 weeks gestation, spent 8 days in NICU for unclear reasons requiring intubation and oxygen. Upon review of patient history and chest x-ray, diagnosis of TB became less likely. This was further confirmed by gastric aspirate revealing no organisms and negative QuantiFERON Gold. CT with oral and IV contrast revealed a right-sided congenital diaphragmatic hernia (CDH) in the foramen of Morgagni. Patient received definitive outpatient surgery in October 2021. At 3-month follow-up there were no surgical complaints and patient reported increased exercise tolerance. DISCUSSION: TB is very rare in the US, even in the Rio Grande Valley where the proportion of cases are higher. This child received 42 doses of TB treatment after a positive PPD and consolidation on chest x-ray. However, x-ray did not clearly indicate TB infection and in fact was suspicious for bowel in the chest cavity. This case clearly indicates the need for careful examination of radiographs and ordering more tests such as the QuantiFERON Gold as needed before jumping to what may seem to be the obvious conclusion. Even though CDH are uncommon and Morgagni hernias are rare making up only 2-3% of CDH, a closer look at the case was warranted. This child's misdiagnosis led to more than simply unnecessary medical treatment, it also led to social stigma for the family that culminated in the father being terminated from his job. This child's surgical repair was delayed due to missed diagnosis of Morgagni hernia in NICU, PICU, and health department and delayed ordering of confirmatory TB tests. Furthermore, patient was referred to surgery in March 2020 but was delayed by 19 months due to COVID-19. The pandemic was also the stimulus for the outpatient nature of the complicated surgery. It is unclear why patient's PPD was positive. It is of note that mother's PPD was also positive due to contact with active TB years prior to child's birth. One hypothesis is this may have caused positive PPD in child and is a future question to pursue. CONCLUSIONS: We want to emphasize to look before you leap and investigate before you treat. There was harm to the child and family done by treating aggressively that could have been prevented and an opportunity to help the child that was delayed. Reference #1: Cowger TL, Wortham JM, Burton DC. Epidemiology of tuberculosis among children and adolescents in the USA, 2007–17: An Analysis of National Surveillance Data. The Lancet Public Health. 2019;4(10). doi:10.1016/s2468-2667(19)30134-3 Reference #2: Leeuwen L, Fitzgerald DA. Congenital diaphragmatic hernia. Journal of Paediatrics and Child Health. 2014;50(9):667-673. doi:10.1111/jpc.12508 Reference #3: Mohamed M, Al-Hillan A, Shah J, Zurkovsky E, Asif A, Hossain M. Symptomatic congenital Morgagni hernia presenting as a chest pain: A case report. Journal of Medical Case Reports. 2020;14(1). doi:10.1186/s13256-019-2336-9 DISCLOSURES: No relevant relationships by Isha Mittal No relevant relationships by Barbara Stewart

Individualising Life Expectancy Is Necessary for Optimal Prescribing.

One possible cause of overprescribing (or insufficient deprescribing) is the failure to explicitly address the individual's life expectancy (LE). For example, if a LE estimate shows the person has six months to live, this should influence the prescribing of a medication that offers benefits only over a much longer LE. Predicting exactly the number of years a person will live is impossible, but probabilistic forecasting is possible and arguably essential, both for the selection of the optimal intervention and for meeting the 'reasonable patient' standard of information about the harms and benefits of alternative options. One side-effect of the COVID-19 pandemic has been to bring mortality into greater prominence, hopefully facilitating its discussion in the clinic as part of the 'new normal'. This paper outlines the case for introducing LE into prescribing decisions as a way of making more individualised decisions and potentially reducing overprescribing. It concentrates on how the clinical task of arriving at individualised estimates of LE might be tackled, especially in the case of the growing number of older patients with heterogeneous sociodemographic characteristics who are experiencing multiple long term conditions of varying severity and are frequently subject to 'polypharmacy'.

Frailty in Diabetic Subjects during COVID-19 and Its Association with HbA1c, Mean Platelet Volume and Monocyte//Lymphocyte Ratio

Background: Frailty is associated with increased risk of hospitalization in diabetic patients. Both SARS-CoV-2 pandemic and type 2 diabetes mellitus contribute to the frailty. In this study we aimed to observe clinical and laboratory indices of the diabetic subjects during COVID-19 pandemic who were either frail or not according to Edmonton frail score. Material and methods: During the pandemic era, 100 consecutive patients with type 2 diabetes mellitus divided into two groups either as frail or non-frail according to the Edmonton Frail Scale scores. Laboratory and clinical features of the frail and non-frail subjects were compared. Results: Frail patients were older than the non-frail diabetics. Blood urea, serum creatinine, eGFR, plasma albumin, total cholesterol, triglyceride, HbA1c, mean platelet volume (MPV), and monocyte lymphocyte ratio (MLR) levels of the frail and non-frail groups were significantly different. Moreover, Edmonton frail score was significantly and positively correlated with blood urea, serum creatinine, MLR, MPV, HbA1c and inversely correlated with eGFR and plasma albumin levels. Conclusions: We think that HbA1c, MPV and MLR could be surrogate markers of frailty in diabetic elderly during COVID-19 outbreak. Strategies to keep them in normal range do not only improve diabetes control but also reduce the risk of frailty in this population.

SMALL-Open surgery versus minimally invasive vacuum-assisted excision for small screen detected breast cancer: A phase 3 randomised trial

Background:. Mammographic screening programmes have been shown to reduce breast cancer mortality. However, they detect many small tumours with favourable biological features which may not progress during a woman's lifetime. These are treated with standard surgery and adjuvant therapies, which have associated morbidities. Thus, there is a need to reduce overtreatment of good prognosis tumours found by screening. Minimally invasive treatment approaches have been described but there is no prospective randomised evidence to support their routine use. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Methods:. SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected good prognosis breast cancers. The main eligibility criteria are age ≥47 years, screen-detected unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in S the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are:1.Non-inferiority comparison of the requirement for a second procedure following excision2.Single arm analysis of local recurrence (LR) at 5 years following VAE. Recruitment of 800 patients over 4 years will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimise recruitment and informed consent. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results:. SMALL opened in December 2019, but recruitment halted in 2020 due to suspension of the NHS BSP for 5 months due to COVID-19. As of 1st July 2021, 55 patients had been approached in 10 centres, with 33 patients randomised (randomisation rate 60%). A further 23 centres are in set-up, with 8 suspended due to the pandemic. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on introducing and discussing SMALL, providing balanced information. on treatment options and explaining randomisation). individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion:. Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme, award 17/42/32.

Hypovitaminosisd on an adult female: From autoimmune conditions to pandemic days

Objective: COVID-19 pandemic was associated with increased risk of hypovitaminosis D due to lockdown regulations and limited outdoor activities, while young adult patients with autoimmune conditions may associated decreased values of 25-hydroxyvitamin D due to copresence of celiac disease, glucocorticoid exposure, malabsorption, overtreatment of autoimmune hypothyroidism, etc. (1-5).We aim to introduce a female case known with autoimmune conditions who was admitted for vitaminD deficiency related symptoms during pandemic. Case report: A 41-year-old, nonsmoker female is admitted for nonspecific muscle cramps, and joints pain, asthenia which is persistent for the last several months in addition to chronic low back pain (which required chronic use of nonsteroid anti-inflammatory medication). Her personal medical background reveals a diagnosis of HLA-B27-positive ankylosing spondylitis that was established seven years before current admission. She is also known with autoimmune thyroiditis with negative antibodies, a diagnostic that was based on suggestive ultrasound features with highly hypoechoic pattern of relative small thyroid gland (and normal thyroid function). She is also confirmed with thrombophilia. She has a negative personal history of confirmed COVID-19 infection and she followed the lockdown restrictions for several weeks. The family medical history is irrelevant. On admission, clinical examination of the thyroid is within normal limits on amenstruated normal weighted female. Biochemistry data points out normal total calcium of 9.45 mg/dL (normal: 8.4-10.3 mg/dL). Endocrine panel shows TSH=1.28 μUI/mL (normal: 0.5-4.5 μUI/mL), free levothyroxine=11.65 pmol/L (normal: 9-19 pmol/L), anti-thyroperoxidase antibodies=10.88 UI/mL (normal: 0-35), anti-thyroglobulin antibodies=10 UI/mL (normal: 0-115 UI/mL). 25-hydroxyvitamin D=10 ng/mL (normal >30 ng/mL) with increased PTH levels and negative antibodies for celiac disease. Supplementation with daily 2000 UI of vitamin D for 12 weeks followed by daily 1000 UI was recommended. Conclusion: The association thrombophilia-hypovitaminosis D has been reported in some patients, but it is rather incidental. Chronic use of antiinflammatory medication may cause malabsorption, and also the potential of a second autoimmune disease at intestinal level may cause this deficiency, but the current pandemic reality has become a new cause of it.

Comparing MammaPrint and BluePrint results between core needle biopsy and surgical resection breast cancer specimens

Goals: The COVID-19 pandemic continues to strain healthcare systems globally. The ESMO COVID-19 adapted recommendations1 advocate for the use of pre-operative/neoadjuvant endocrine therapy as a strategy to defer surgery by 6–12 months in clinical stage I-II breast cancers to prioritize resources for patients that require urgent care. Accurate risk assessment is an integral component of this prioritization process. Adjuvant studies such as MINDACT showed that up to 46% of clinically high risk tumors were classified as genomic Low Risk with MammaPrint, and still have excellent outcomes at 8-yrs with endocrine therapy alone, highlighting the potential for overtreatment if using clinical-risk alone. Here, gene expression results with MammaPrint (MP) and BluePrint (BP) were compared between pre-operative core needle biopsy (CNB) and postoperative surgical resection (SR) specimens to evaluate test performance across specimen type. Methods: 10,574 routine diagnostic samples from outside the US submitted to Agendia between Jan 2017 and Oct 2020 were included in this study.MP and BP testingwere processed according to standard FFPE microarray procedures. MP was used to stratify samples into Ultra LowRisk (UL), LowRisk (LR), and High Risk (HR). BPwas used to classify samples into Basal, Luminal or HER2-type. MP Index (MPI) distribution on BP defined Luminal-type tumors were compared between CNB and SR samples. Comparative “logistics metrics” (avg. turnaround time [TAT] and success rate) were also assessed between these specimen types. Results: 10% of samples were CNB and 90% were SR (Table 1). BP Basal, Luminal and HER2-type distributions were 2%, 97%, and 1% respectively for CNB samples and 1%, 98.6%, and 0.4% respectively for SR samples. Within Luminal-type tumors (majority of the samples), the frequency of UL, LR, and HR results were 14%, 61%, and 39% for CNB, and 13%, 58%, and 42% for SR, respectively. Overall, MP Index distributions were similar between samples tested from CNB vs. SR. Average TAT and success rate % between CNB and SR were similar (Table 2).(Table Presented)Definitions: Turnaround Time (TAT) is calculated from the time a specimen is received at the laboratory to the time a result is available. Success % excludes test failures due to insufficient RNA yield % and sub-optimal RNA quality, and evaluates the total number of specimens that have met the pre-requisite 30% minimum invasive tumor requirement that have a valid result. Conclusion(s): The frequency of each MP risk group as well as the distribution pattern of MP Index were essentially identical between CNB and SR samples, indicating comparable performance regardless of specimen type. With timely TAT and no meaningful difference in MPI distribution between CNB and SR specimens, pre-operative use of MP+BP genomic testing on CNB can be incorporated into the preoperative treatment decision making process. Conflict of Interest: Employee of Agendia, equity/stock ownership interest.