Upskilling haematological services for WGS and germline assessments through a regional skin biopsy training programme

NHS England Genomics introduced whole genome sequencing (WGS) with standard-of- care (SoC) genetic testing for haemato-oncology patients who meet eligibility criteria, including patients with acute leukaemia across all ages, and exhausted SoC testing. Alongside, the role of germline mutations in haematological cancers is becoming increasingly recognised. DNA samples are required from the malignant cells (somatic sample) via a bone marrow aspirate, and from non-malignant cells (germline sample) for comparator analysis. Skin biopsy is considered the gold-standard tissue to provide a source of fibroblast DNA for germline analysis. Performing skin punch biopsies is not within the traditional skillset for haematology teams and upskilling is necessary to deliver WGS/germline testing safely, independently and sustainably. A teaching programme was designed and piloted by the dermatology and haematology teams in Sheffield and delivered throughout the NHS trusts in North East & Yorkshire Genomic Laboratory Hub. The training programme consisted of a 90-min session, slides, video and practical biopsy on pork belly or synthetic skin, designed to teach up to six students at one time. To disseminate best practice, the standard operating procedure and patient information used routinely in Sheffield were shared, to be adapted for local service delivery. From January 2021 to December 2022, 136 haematology staff from 11 hospitals, including 34 consultants, 41 registrars, 34 nurses and 8 physician associates, across the NEY GLH region completed the skin biopsy training programme. Feedback from the course was outstanding, with consistently high scores in all categories. Practical components of the course were especially valued;98.6% (71/72) trainees scored the practical element of the programme a top score of 5 out of 5, highlighting that despite the challenges of delivering face-to- face teaching due to COVID-19, teaching of practical skills was highly valued;training in this way could not have been replicated virtually. Costs of the programme have been approximately 16 000, including consultant input and teaching/educational materials. Recent support has been provided by a separately funded Genomic Nurse Practitioner (GNP), with succession planning for the GNP to take over leadership from the consultant dermatologist. Plans are in place to use the remaining budget to disseminate the programme nationally. Our training programme has shown that skin biopsy can be formally embedded into training for haematology consultants, trainees, nursing team, and physician associates. Delivery of training can be effective and affordable across regional GLHs with appropriate leadership and inter-speciality coordination, and ultimately sustainable with specialist nursing staff, including GNPs.

Evaluation of Lung Ultrasound in Assessment of Critically Ill patients in Respiratory Intensive Care Unit

Reaching a proper diagnosis for critically ill patients is like collecting pieces of puzzle and bed side lung ultrasound (LUS) becomes a crucial piece complementary to clinical and laboratory pieces. It is a bed side, real time tool for diagnosis of patients in ICU who are critical to be transferred to radiology unit especially in Covid-19 pandemic with risk of infection transmission. The aim was to evaluate the accuracy of lung ultrasound in assessment of critically ill patients admitted to Respiratory Intensive Care Unit (RICU), moreover to assess its diagnostic performance in different pulmonary diseases as compared to the gold standard approach accordingly. This observational prospective (cross sectional) study with a total 183 patients who met the inclusion criteria,were selected from patients admitted at the RICU;Chest Department, Zagazig University Hospitals, during the period from September 2019 to September 2021. LUS examination was performed to diagnose the different pulmonary diseases causing RF. All cases were examined by LUS on admission. From a total 183 patients, 111 patients 60.7% were males and 72 patients 39.3% were females, with a mean age of 56+/-12.77 years, 130 patients were breathing spontaneously received conservative management with O2 therapy, 32 patients needed NIV while 21 patients needed IMV with ETT. Exacerbated COPD was the most common disease finally diagnosed followed by bacterial pneumonia, exacerbated ILD, post Covid-19 fibrosis and pulmonary embolism in32, 29,27, 19 and 11 patients respectively with corresponding diagnostic accuracy of LUS 97.3%, AUC=0.943, 93.9% (AUC=0.922), 96.7%(AUC=0.920), 97.8%, AUC=0.895, and 97.8% respectively, while Covid-19 pneumonia was the final diagnosis in 8 patients with LUS diagnostic accuracy of 97.8% (AUC=0.869) with no statistical significant difference p-value=0.818 with bacterial pneumonia in distribution of US profiles. A profile was the commonest detected US profile among the studied patients followed by B profile, C profile, A/B profile and A' profile in 37.2%, 24.6%, 15.8% 4.9%, and 3.8% of cases respectively. Bed side LUS has a reliable, valuable diagnostic performance when integrated with clinical and laboratory data for the diagnosis of most pulmonary diseases in RICU.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

GDM diagnosis criteria: Standard and Covid-19 criteria

Aim: Standard diagnosis of gestational diabetes (GDM) is based on the Oral Glucose Tolerance test (OGTT). During the Covid-19 outbreak, due to Covid restrictions, criteria were modified i.e Fasting Blood Glucose >=5.3 and/ or HbA1c >= 39 for diagnosis of GDM. After the lifting of the Covid restrictions, the standard criteria were reimplemented and on analyzing the data, it was highlighted that some of the patients could have tested negative for GDM based on Covid Criteria. Method(s): We analyzed the data of 43 patients based on standard criteria (OGTT and HbA1c) after Covid restrictions, with the following results. Result(s): 11/43(28%) patients who were diagnosed on the basis of standard criteria could have been missed based on Covid criteria. Out of 11 deliveries, 2 babies with weight above 4 kg. There were no admissions to NICU. One patient had postpartum hemorrhage with 670 mL of blood loss. Conclusion(s): This was a retrospective study in which we analyzed the data of 45 pregnant females diagnosed with GDM based on testing using the Covid criteria and compared this to 43 pregnant females who were diagnosed with GDM on the basis of OGTT based on GOLD standard NICE criteria. In addition, we also examined maternal and obstetric outcomes in both groups such as the mode of delivery, the baby's birth weight, the incidence of shoulder dystocia, mean blood loss (MBL), and NICU admission. We understand that Covid GDM diagnosis was a necessity of time. In this study, we want to learn what could have been missed with that diagnostic criteria. For future pandemics, we need to revise our diagnostic criteria to avoid the risk of underdiagnosing GDM and associated complications.

Comparison of Diagnostic Accuracy of CRP Versus Ferritin in COVID Patients as a Marker of Severity of Disease Taking who Severity Classification as Gold Standard

Objective: To determine the diagnostic accuracy of elevated C reactive protein (CRP) and ferritin in predicting severe Covid-19 infection using the World Health Organization's (WHO) Covid-19 severity classification as gold standard. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at the Pak Emirates Military Hospital, Rawalpindi, from January 1st 2021 till April 30th 2021. Ethical review committee's (ERC) approval was taken and good clinical practice guidelines were followed. Material(s) and Method(s): Baseline blood samples were sent to the hospital laboratory for the measurement of C reactive protein and ferritin levels. PCR was taken as gold standard for the diagnosis of Corona virus disease. Patients were classified into severe and non-severe categories using WHO classification of severity. Sensitivity, specificity, diagnostic accuracy, negative predictive value and positive predictive value were calculated for elevated CRP and ferritin. Result(s): There were 65 (57.5%) patients who had severe Covid-19 disease and 48 (42.5%) patients who had non-severe Covid-19 disease. Among the patients with severe Covid-19, 57 (87.7%) had elevated CRP levels, and 50 (76.9%) patients had elevated ferritin levels. Testing ferritin levels, against the severity of Covid-19 patients, there was a sensitivity of 76.9%, specificity of 79.2%, positive predictive value (PPV) of 83.3%, negative predictive value (NPV) of 71.7% and diagnostic accuracy of 77.8%. Testing CRP levels, there was a sensitivity of 87.7%, specificity of 85.4%, PPV of 89.1%, NPV of 83.6% and diagnostic accuracy of 86.7%. Conclusion(s): The results from our study show that CRP has a slightly improved diagnostic accuracy as compared to ferritin. However, both these markers have value in the prediction of severity of Covid-19 infection.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Towards gold standard care for peripartum women admitted to general intensive care units

Introduction: Critically-ill obstetric patients admitted to general intensive care units (ICU) are a rare and unique population for whom excellent care is essential to prevent devastating physical and psychological morbidity. Admissions are often unanticipated and can present challenges to obstetric and intensive care MDTs. 2018 Enhanced Maternal Care (EMC) Guidelines provide standards for caring for these women, and the 2022 Ockenden review exposed the association of peripartum ICU admission with undertreated psychological trauma and a desire for individualised debriefing [1,2]. We audited the care of obstetric admissions to general ICUs in our quaternary centre. We sought evidence of psychological morbidity to improve follow-up pathways in line with 2022 Ockenden actions. Method(s): Retrospective online case note review of maternity admissions to general ICUs between 1/1/2021-1/1/2022 compared to EMC audit standards. Exclusion criteria: <22/40 gestation, >6/52 postpartum and admissions to our level 2 labour ward high dependency unit. Result(s): 25 patients were admitted to general ICUs over 12 months. Median age was 35-39 years, mean parity was 1. The commonest indication was obstetric haemorrhage (n = 10). 15 of 25 patients required level 3 care, median length of stay was 1.5 days. Documentation of daily obstetric MDT ward round was variable, as was mother-baby contact. 0 of 25 women were seen in obstetric anaesthesia clinic after discharge, only 1 received outpatient ICU follow-up. 50% of postnatal admissions (n = 14) had documentation of significant psychological distress. In response a local checklist was developed with key colleagues to support collaborative working and standardise quality care. It includes automatic referral into obstetric anaesthesia clinic and access to a novel perinatal mental health service. Discussion(s): A peripartum admission to ICU is highly likely to be experienced as traumatic [2]. The incidence of obstetric ICU admissions may increase in the context of greater clinical complexity of the UK pregnant population and COVID-19, whilst the non-anaesthetic ICU workforce may have little obstetric training. Obstetric anaesthetists are therefore uniquely skilled to facilitate quality resuscitation and referral to ICU, but gold-standard holistic care extends beyond admission. We believe regular audit and dedicated local care pathways which incorporate proactive debriefing and psychological health can improve the care of this important group of women.Copyright © 2023 Elsevier Ltd

Development and Evaluation of a Textanalytics Algorithm for Automated Application of the Bsr Covid-19 Shielding Criteria in Rheumatology Patients

Background/Aims In April 2020 the British Society for Rheumatology (BSR) issued a risk stratification guide to identify patients at the highest risk of COVID-19 requiring shielding. This guidance was based on patients' age, comorbidities, and immunosuppressive therapies - including biologics that are not captured in primary care records. This meant rheumatologists needed to manually review outpatient letters to score patients' risk. The process required considerable clinician time, with shielding decisions not always transparently communicated. Our aim was to develop an automated shielding algorithm by text-mining outpatient letter diagnoses and medications, reducing the need for future manual review. Methods Rheumatology outpatient letters from Salford Royal Hospital, a large UK tertiary hospital, were retrieved between 2013-2020. The two most recent letters for each patient were extracted, created before 01.04.2020 when BSR guidance was published. Free-text diagnoses were processed using Intelligent Medical Objects software1 (Concept Tagger), which utilised interface terminology for each condition mapped to a SNOMED-CT code. We developed the Medication Concept Recognition tool (MedCore Named Entity Recognition) to retrieve medications type, dose, duration and status (active/past) at the time of the letter. The medication status was established based on the heading where they appeared (e.g. past medications, current medications), but incorporated additional information such as medication stop dates. The age, diagnosis and medication variables were then combined to output the BSR shielding score. The algorithm's performance was calculated using clinical review as the gold standard. Results To allow for the comparison with manual decisions, we focused on all 895 patients who were reviewed clinically. 64 patients (7.1%) had not consented for their data to be used for research as part of the national opt-out scheme. After removing duplicates, 803 patients were used to run the algorithm. 11,558 free-text diagnoses were extracted and mapped to SNOMED CT, with 15,003 free-text medications (that included past, present and any planned treatment). The automated shielding algorithm demonstrated a sensitivity of 80.3% (95% CI: 74.7, 85.2%) and specificity of 92.2% (95% CI: 89.7, 94.2%). Positive likelihood ratio was 10.3 (95% CI: 7.7, 13.7), negative likelihood ratio was 0.21 (95% CI: 0.16, 0.28), F1 score was 0.81. False positive rate was 7.9%, whilst false negative rate was 19.7%. Further evaluation of false positives/negatives revealed clinician interpretation of BSR guidance and misclassification of medications status were important contributing factors. Conclusion An automated algorithm for risk stratification has several advantages including reducing clinician time for manual review to allow more time for direct care, improving efficiency and transparently communicating decisions based on individual risk. With further development, it has the potential to be adapted for future public health initiatives that requires prompt automated review of hospital outpatient letters.

Rheumatology Advice Lines: How to Manage Rising Demand and Limited Capacity?

Background/Aims Advice lines services (ALS) are a key aspect of providing coordinated patient care in rheumatology. Demand for rapid access to specialist advice increased during the pandemic due to the disruption of routine outpatient services but it is not clear whether this demand is sustained. We aimed to investigate the changes in demand for ALS, how this varied pre/during COVID-19 and audit the effect upon response times. We also aimed to assess the impact of introducing an email advice service on demand. Methods We audited the number of advice line contacts of a single rheumatology department, serving a population of 500,000 people. The telephone adviceline is provided as an answer machine with an email advice service set up in April 2020. The outcome of each contact is recorded as a) advice only b) action required (e.g., prescription, blood test, GP letter) or c) required appointment (monitor/nurse/ medical). We audited response times using the RCN guidelines of a two-day response1 as the gold standard. Results Demand for advice had been increasing pre-COVID with an average of 368 calls/month (1/1/19-1/7/19) to 420/month (1/7/19-31/12/19). Sixty percent were advice only calls but 27% required additional action. Response times met the audit standard in 97% of cases pre-COVID. During the first two months of COVID demand for advice services doubled, however demand continued to rise although outcomes were similar (Table 1). As the number of contacts increased the proportion of telephone contacts responded to within the audit standard fell. Numbers of email contacts were variable, but response times exceeded the audit standard. Conclusion This audit demonstrates the demand of adviceline services has continued to increase throughout the pandemic and beyond, impacting the ability of services to respond within a timely manner. Ongoing QI work is assessing mechanisms to manage increased demand (using healthcare support workers to triage calls) and investigating reasons for accessing ALS to ensure appropriate advice is available. (Table Presented).

Indirect Calorimetry Critical in Identifying Early Hypometabolism and Late-Stage Hypermetabolism in Post-surgical Patients

Background: Indirect calorimetry (IC) is the gold-standard procedure for measuring resting energy expenditure (REE) in hospitalized patients. Predictive energy equations commonly use static variables and rarely account for changes in REE throughout hospitalization. We hypothesize that predictive equations are typically inaccurate in surgical intensive care unit (ICU) patients. More specifically, we hypothesize that predictive equations often overpredict measured resting energy expenditure (mREE) in early-stage critical illness and underpredict needs later in surgical ICU stay, leading to over-/under-feeding and associated complications. Method(s): This prospective observational trial enrolled surgical ICU patients who underwent emergent or urgent operations for abdominal trauma, perforated viscus, or ischemic bowel within 72 hours of their surgical procedure. Metabolic assessments were performed using the COSMED Q-NRG + Metabolic Monitor ventilator, mask, and canopy at regular intervals during and post ICU admission until hospital discharge. Measurements were categorized by post-surgical intervention ICU admission days 0-3, 4-7, 8-14, 15-21, and 22-28. Patients with multiple measurements taken during the same time interval were averaged. mREE reported in calories (kcal) per kilogram (kg) of admission body weight per day were compared in obese (BMI > 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. Compared to IC, the Mifflin St Jeor (MSJ) equation determined predicted REE using ICU admission anthropometrics. Data are reported as mean+/-standard error of the mean (SEM) and median (interquartile range), and a two-sided p-value of <0.05 was determined significant. Result(s): In total, 18 surgical ICU patients who contributed 47 IC measurements were included in the analysis (Table 1). Most measures were obtained within the first 7 days of post-surgical ICU admission (72%). mREE peaked between days 8-14 in obese and non-obese subgroups (20.6 vs 28.5 kcal/kg;p = 0.02) and was lowest during 0-3 days of post-surgical ICU admission in both groups. Across all 5-time intervals, average kcal/ kg ranged from 14.7-20.6 among obese patients and from 20.1-28.5 in non-obese counterparts (Table 2). Non-obese patients had higher mREE per kg of body weight than obese patients at all time points (Figure 1). MSJ over-predicted mREE during the first 7 days post ICU admission in non-obese patients and within the first 3 days in obese patients and underpredicted mREE in both groups thereafter. Conclusion(s): Equations such as MSJ over- and under-predict mREE in post-operative surgical ICU patients depending on the days elapsed since post-surgical ICU admission. ASPEN's current guideline recommendation of 12-25 kcal/kg may also underfeed post-surgical populations while 25 kcal/kg may not support hypermetabolism among non-obese patients seen in week 2 following post-surgical ICU admission. Alternatively, MSJ multiplied by a 1.2 activity factor may account for hypermetabolism during this time. Notably, non-obese patients experienced greater hypermetabolism than obese patients during week 2 which is consistent with our previously published data in mechanically ventilated COVID- 19 patients. Additionally, the striking dichotomy between the mREE of obese and non-obese patients at all post-surgical time points should be considered in the clinical care of patients. Ultimately, IC remains the gold-standard means of measuring REE and is a critical tool to capture the dynamic nature of energy requirements in post-surgical populations as weight-based and predictive equations continually fall short. (Table Presented).

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Neutralising antibodies (NAbs) against SARS-CoV-2 in BNT162b2 vaccine recipients with a history of advanced HIV infection: cPass as a simpler alternative to gold-standard tests

Background: Established SARS-CoV-2 NAb tests are labor-intensive. We prospectively measured NAbs vs Wuhan-1 and Omicron BA.2 using the novel GenScript cPass assay and examined correlations with responses measured by gold-standard plaque reduction neutralisation test (PRNT) (Cotugno, Ruggiero et al. Cell Rep 2021) and with anti-Spike IgG quantified by Roche Elecsys. Given the paucity of data, we selected BNT162b2 vaccine recipients with a history of advanced HIV infection (prior AIDS-defining conditions and/or nadir CD4 <200 cells). Method(s): In Mar 2021-Apr 2022, 55 PWH received 2 vaccine doses median 3 weeks apart [IQR 3-3] and a 3rd dose 27 weeks later [23-31]. Plasma samples (n=147) were stored immediately before dose-1 (T0), median 4 weeks [3-5] after dose-2 (T1) and median 13 weeks [9-19] after dose-3 (T2) for batch testing. Result(s): Participants' characteristics: 74% male, 85% white, all on ART, 82% HIV-RNA <50 cps/ml;median age 55 years, ART duration 7 years, nadir CD4 83 cells [36-211], current CD4 440 cells [270-710], CD4:CD8 ratio 0.6 [0.4-1.0];73% had a history of advanced HIV infection;15% received a COVID-19 diagnosis during the study. At T0, T1 and T2, proportions with quantifiable anti-S IgG (>0.8 U/ml) were 11/49 (22%), 50/54 (93%) and 43/43 (100%), respectively;their median anti-S IgG titres were 30 [15-124], 15949 [596-3389] and 8527 [3146-17190] U/ml. Proportions showing Wuhan-1 neutralisation by cPass were 6/50 (12%), 45/53 (85%) and 40/43 (93%), with median neutralisations of 67% [47-70], 97% [91-98] and 98% [98-98] and corresponding NAb titres of 1332 [792-1436], 5354 [3529-6187] and 6242 [5765-6766] U/ml. At T2, 25/28 (89%) showed BA.2 neutralisation by cPass (median 83% [68-93];NAb titre 7836 [3172-12173] U/ml) (Fig 1A). Two participants lacking NAbs at T2 had a history of advanced HIV infection. cPass data were highly correlated with anti-S IgG titres (rho 0.82;p<0.0001) and with PRNT data for both Wuhan-1 (n=27, Fig 1B) and Omicron BA.2 (n=28, Fig 1C). Conclusion(s): cPAss offers a simple methodology for measuring SARS-CoV-2 NAbs. Despite prior advanced HIV infection, neutralising activity improved with successive vaccinations and most participants showed NAbs against both Wuhan-1 and Omicron BA.2 after 3 vaccine doses. (Figure Presented).

Human-Centered Design in Response to a Pandemic: A Health System and Innovation Center Collaboration

Purpose of Study In the spring of 2020, the coronavirus pandemic brought new challenges to healthcare systems as the rising demand for protective equipment led to product and resource inequalities around the globe. The inability to safeguard workers led to increased infection rates and deaths of healthcare professionals worldwide. The purpose of this study is to evaluate the response of an in-house innovation committee to meet the unforeseen needs faced by healthcare systems during an acute medical crisis. Methods Used Housed directly within the University of Utah's health system (U Health), The Center for Medical Innovation (CMI) teamed up with the hospital's administration, BME, COVID task force, and occupational health to create an innovative think-tank to tackle the challenges brought in by the coronavirus pandemic, with the purpose of stratifying clinical needs based upon acuity, frequency, and urgency. While prioritizing equipment needs, CMI used human-centered design to analyze common industry practices, engineer comparable solutions from commercially available materials, test reimagined products against known gold-standards, and create open-source assembly guides that allowed others facing similar shortages to do the same. Summary of Results The close-working relationship between CMI and U Health allowed for the rapid identification, innovation, and engineering of products that met the needs of healthcare workers during the months following the COVID pandemic. Many of these were directly adopted in clinical settings, including aerosol containment tents, powered air-purifying respirators, and self-testing stations. Additionally, CMI identified and engineered 20 additional readily producible, rapid-response products in anticipation of future needs, such as a bubble CPAP, containment boxes, and re-usable PPE. From these, dozens of open source, 'Improvised Personal Protective Equipment' manuals were shared with global partners to address the inequality of medical equipment in lowresource settings. Conclusions The rapid development of easily-producible, lowcost solutions for acute clinical needs-especially those faced by the equipment shortages seen during a pandemic-is improved via the partnership between health systems and a center for medical innovation.

Can You Spare 100 Days? The Allogeneic Hematopoietic Cell Transplant Caregiver Requirement

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for patients diagnosed with blood cancers (such as acute myeloid leukemia) and blood disorders (such as sickle cell disease). It is a resource-intensive treatment that generally requires a long hospital stay and recovery period. If continuous caregiver support is not available, alloHCT likely will not be a treatment option. To learn more about caregiver requirements and perspectives on those requirements, we conducted web-based focus groups with alloHCT social workers who worked with adult patients at United States (US) transplant centers (TCs) from May-July 2022. Web-based interviews with adult alloHCT recipients,caregivers of adult alloHCT recipients, and physicians/advanced practice professionals will also be conducted. Twenty-two social workers from TCs across the US (Midwest [n=8];West [n=5];Northeast: [n=5];South, [n=4]) and with varying volumes (median: 97 alloHCTs performed/year) participated. All noted their TC required a caregiver to proceed to alloHCT. However, there was variation across TCs in the length of time a recipient was required to have a caregiver, the distance/time needed to stay near the TC post-alloHCT, and COVID-19 vaccination requirements. The majority of participants also noted variance among the transplant team in allowing exceptions for caregiver requirements. All participants noted it would be helpful to have a 'gold standard' of requirements across TCs, though there was discussion about what such a standard would include, as well as the need for flexibility to account for different patient and TC needs. Social workers were also asked to identify patient barriers to meeting the caregiver requirement;common barriers included patients feeling they did not have anyone to ask to be a caregiver, the need to relocate closer to the TC, and financial barriers. The impact of the COVID-19 pandemic was also noted (e.g., vaccination requirements, and increased telework allowing more flexibility for caregivers). In analysis of the first of four populations interviewed in this study, social workers reported variation in caregiver requirements across TCs. Finding a caregiver is one of many barriers patients face in accessing alloHCT. Though this variation may allow for some flexibility, it may also contribute to access barriers. This study focused on those who received an alloHCT, but further research is needed to learn about barriers faced by those unable to access alloHCT. Results from this and other cohorts will describe current practices related to caregiver requirements and help inform the development of new programs to reduce caregiver-related barriers to alloHCT.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Ethical Lessons Learned from the COVID-19 Pandemic in Perinatal Medicine

The COVID-19 pandemic is unprecedented in our lifetime, especially in perinatology. The gold standard is to strongly recommend COVID-19 vaccinations to those trying to get pregnant, to those who are pregnant, and to those who are postpartum. When the benefits of vaccines far outweigh the risks, it is unethical to disseminate wrong information and discourage patients from becoming vaccinated. COVID-19 vaccinations and boosters prevent severe diseases and adverse pregnancy and neonatal outcomes. A pregnant patient's vaccination also protects the newborn infant because maternal antibodies protect the fetus and newborn. COVID-19 vaccinations and boosters in pregnancy are safe for the pregnant patient and her fetus. The three root causes of physician hesitancy-misapplication of therapeutic nihilism, misapplication of shared decision-making, and misapplication of respect for autonomy should not be ignored and need to be addressed. It is important that we heed Brent 's insightful recommendations. Doing nothing with respect to vaccination is not an option, whether it applies to COVID-19 vaccines or to future pandemics. Physician hesitation is not an option. When there is sufficient evidence of vaccine safety and effectiveness without documented risks, vaccine recommendations before, during, and after pregnancy should be explicitly made to prevent maternal, fetal, and neonatal morbidity and mortality.Copyright © The Author(s). 2023.

A comparison of peripheral blood stem cell collection outcomes for multiple myeloma, mobilization matters in the era of IMiD induction

Collection of peripheral blood stem cells (PBSCs) for autologous stem cell transplant (ASCT) requires mobilization from the bone marrow. There is variation in mobilization choice;during the COVID-19 pandemic BSBMT&CT guidelines recommended using granulocyte-colony stimulating factor (G-CSF) alone to minimize the use of chemotherapy. We report on the impact of mobilization regimen on stem cell collection, and whether IMiD-containing induction therapy impacts on mobilization and consequently transplant engraftment times for 83 patients undergoing ASCT at Leeds Teaching Hospitals. Cyclophosphamide plus G-CSF (cyclo-G) mobilization yielded more CD34+ cells (8.94 vs. 4.88 x106/kg, p = < 0.0001) over fewer days (1.6 vs. 2.4 days, p = 0.007), and required fewer doses of salvage Plerixafor than G-CSF only (13.6% vs. 35%, p = 0.0407). IMiD-containing induction impaired all of these factors. CD34+ doses > 8x106/kg were more frequent with Cyclo-G (62% vs. 11%, p = 0.0001), including for those receiving IMiD 1st line induction (50% vs. 13.3%, p = 0.0381). Note that 92.6% of those receiving IMiD-free inductions were mobilized with Cyclo-G. The novel agents used in modern induction regimens (e.g Daratumumab) have been shown to impair yields, increasing the importance of optimizing mobilization regimens in the first instance. Furthermore, as cellular therapies become established in the management of multiple myeloma emerging data highlights the potential benefits of stem cell top up in the management of the haematological toxicities of these therapies. Our findings support re-adoption of Cyclo-G as the gold standard for mobilization to optimize PBSC harvesting and ensure sufficient cells for subsequent ASCTs.Copyright © 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.

Addressing the Increasing Signs of Fatigue Post-Pandemic in Rock Springs, Wyoming

Purpose of Study: Fatigue is a confusing blend of feelings and actions that makes us feel strangely out of place. It has a significant negative impact on physical and emotional well-being, affecting the quality of life of patients. Fatigue has been poorly understood, due to its complex differential diagnosis, ranging from endocrine and respiratory to psychiatric disorders. In Wyoming, there has been an increase in anxiety and depression symptoms during the pandemic. Additionally, State budget cuts have caused a reduction in mental health services. Therefore, Primary care doctors must discuss, inform, and screen for mental health problems related to fatigue in the community due to the combination of rising mental health symptoms and declining mental health resources. Increasing screening for fatigue, using a Fatigue Assessment Scale (FAS), as an early intervention to address physical and/or mental Fatigue in primary care clinics, in Rock Springs, Wyoming. Methods Used: In primary care, there has been an increasing number of patients presenting with signs of fatigue, especially after the pandemic, which needs to be better understood. Currently, there is not a widespread gold-standard screening tool for Fatigue in primary care practice. Upon literature review, a simple three min, 10-item self-report questionnaire called the Fatigue Assessment Scale (FAS) addresses both physical and mental fatigue, ranging from lack of motivation to lack of energy. Summary of Results: FAS should be integrated into primary care clinics in Rock Springs, Wyoming with other screening questionnaires such as the anxiety/depression screening, to screen for and measure the severity of fatigue. Patients with physical fatigue along with shortness of breath and recent COVID exposure can benefit from pulmonary rehabilitation, whereas Patients with mental fatigue along with nausea, vomiting, and a recent chemotherapy session, can benefit from a counseling session and blood tests. Conclusion(s): FAS along with the history of present illness and physical exam will help guide the diagnosis with different clinical tests, blood tests, imagining studies, physical therapy, rehabilitation, and/or medications.

Use of artificial intelligence for point-of-care echocardiographic assessment of left ventricular ejection fraction among COVID-19 patients

Background: The association between COVID-19 infection and the cardiovascular system has been well described. Isolation precautions limit the use of formal echocardiography in this setting. Artificial intelligence (AI) utilization using a hand-held device in these patients can be a reliable tool for left ventricular ejection fraction (LVEF) assessment. Aim(s): To prospectively investigate the accuracy of AI-base tool for LVEF assessment using a hand-held echocardiogram in patients with COVID-19. Method(s): From April-28 through July-26, 2020, consecutive patients with COVID-19 underwent a real-time LVEF assessment within 48-h of admission using a hand-held echocardiogram evaluation (Vscan Extend) equipped with LVivoEF, an AI-based tool that automatically evaluates LVEF. The examinations were further analyzed off-line by a blinded fellowshiptrained echocardiographer for LVEF as a gold standard. Result(s): Among 42 patients, 21 (50%) were male (aged 53.3+/-17.8 years, mean BMI 27.6+/-5.1 kg/m2). Seven (16.7%) patients couldn't turn on their left side and three (7.1%) couldn't maintain effective communication. The mean length of each echocardiogram study was 6.8+/-2.2 minutes, battery usage was 13.4+/-4.9%, and mean operator-to-patient proximity was 64.5+/-9.3 cm. A fair to good correlation was demonstrated between the AI and the echocardiographer LVEF assessment (Pearson's correlation of 0.691, p<0.001). An almost perfect agreement was demonstrated between the AI and the echocardiographer for LVEF using a threshold of 45% (kappa=0.806, p<0.001). The sensitivity of focused echocardiogram for 45% LVEF threshold is 85.7%, specificity is 97.1% with a PPV of 85.7% and NPV of 97.1%. Conclusion(s): An AI-based algorithm incorporated into an existing handheld echocardiogram device can be reliably utilized as a decision support tool for automatic real-time LVEF assessment among COVID-19 patients.

The Evolution of SARS-CoV-2 Infection in the Pediatric Ward at St. Andrew's County Emergency Clinical Hospital Constanta

In the period April 24, 2020 - December 31, 2021 at Saint Andrew's County Emergency Clinical Hospital's Molecular Biology Laboratory were performed 2856 RT-PCR tests on childrens. This method consists of two steps: extraction and amplification. RT-PCR is the golden standard to diagnose infection with Covid-19. The tests were performed on patients of both genders and under 18 years old. Statistics show that both male and female patients were affected by Sars-Cov-2 in relatively equal proportions: in the first year (male 46% and female 54%), followed by the next year (male 48% and female 52%). The results concluding, that during the study, in 2020, 6.98% of the total number of tests came out positive, 92.32% came out negative, 0.70% inconclusive. In 2021, 4.21% of the total number of tests came out positive, 95.56% came out negative, 0.23% inconclusive. This study highlights the situation of Covid-19 cases encountered at childrens from the Pediatric section diagnosed in Constanta, Romania.Copyright © 2022 Ramona-Anca Sterian et al., published by Sciendo.

Moving to accelerated protocols of tDCS in schizophrenic catatonia: A case report

This is a case report of a 74-year-old woman with catatonic schizophrenia who was treated with transcranial Direct Current Stimulation (tDCS) in place of electroconvulsive therapy (ECT) during the Covid-19 pandemic that impacted access to ECT facilities. In 2021, the exceptional number of patients infected with SARS-Cov-2 led the French public hospital system to adjust its organization, temporarily redirecting anesthetists from ECT departments to ICUs. Our patient, who was hospitalized via the emergency department, presented schizophrenia with catatonic features. Due to the pandemic, ECT, which is considered the gold standard treatment for this condition, was not available. Therefore, tDCS, a neuromodulation technique that doesn't require general anesthesia, was recommended for this patient, and was delivered at the relatively (compared to standard protocols) accelerated rate of five sessions a day, five days a week. This protocol was chosen as accelerated rTMS had been shown to be effective against depression in recent trials (Cole et al. 2021), and one study had also reported this exact protocol as effective and harmless for a patient with schizophrenia (Mondino et al. 2021). The Bush-Francis Catatonia Rating Scale (BFCRS) was used to evaluate the severity of the catatonia. After 49 sessions, the clinical response was meaningful, with a BFCRS score of 16, compared to 36 at baseline. We then moved to five sessions a day, three days a week, and then two days a week. After 80 sessions, we noted the complete disappearance of catatonia (BFCRS = 6). This case provides evidence for the feasibility and tolerability of accelerated tDCS for patients with catatonia. Accelerated tDCS represents a potential alternative to ECT in the treatment of catatonia, and needs further randomized clinical studies to confirm its efficacy. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tdcs, catatonia, covid-19, ECTCopyright © 2023

Subclinical Myocardial Leukocyte Infiltration after COVID-19 Vaccination in HeartTransplant Recipients

Background: mRNA-based COVID-19 vaccines have been reported to rarely cause myocarditis. Although myocardial biopsy is considered gold standard in the diagnosis of myocarditis, no standardized study following COVID-19 vaccination in humans was performed so far. Since heart transplant (HTX) recipients frequently undergo routine myocardial biopsy, we here aimed to investigate effects of COVID-19 vaccination by analyzing myocardial inflammation by state-of-the-art quantitative immunohistochemistry. Method(s): Consecutive patients after HTX who underwent routine endomyocardial biopsies at a median of 167 days before and 136 days after their first COVID-19 vaccination with a mRNA vaccine were included and divided into groups with and without inflammatory response following vaccination, defined as increased number of CD3+ lymphocytes >14/mm2. Patients with histological signs of rejection (ISHLT Grade >1) or >14 CD3+ lymphocytes/mm2 at baseline were excluded. Afterward clinical characteristics of patients with inflammatory response were screened for signs of myocarditis. Result(s): The final analysis included 46 patients with a median age of 63 years and a time post-HTX of 2.4 years. Immunosuppressive therapy remained unchanged between biopsies. 36 (78%) patients remained below the cut-off of 14 CD3+ lymphocytes/mm2. However, in 10 (22%) recipients, we detected significant leucocyte infiltration by quantitative analysis of endomyocardial biopsies following vaccination (4 vs. 33.7 leucocytes/mm2, p = 0.001). Groups did not differ in age (63 vs. 57 years, p = 0.21), body mass index (25 vs. 24 kg/m2, p = 0.24), NYHA-class (>=2 in 19 vs. 10%, p = 0.4), NTProBNP levels (592 vs. 514 ng/L, p = 0.55) or myocardial CD3+ cell count (4.9 vs. 2.6 cells/mm2, p = 0.07) before vaccination. Patients with leucocyte infiltration remained clinical inapparent with stable NYHA class (>=2 in 10 vs. 20%, p = 0.99) and depicted no increased NT-ProBNP levels (514 vs. 478 ng/L, p = 0.03). No hospitalizations due to suspected myocarditis were reported. Conclusion(s): For the first time, we report subclinical myocardial leucocyte infiltration following COVID-19 mRNA vaccination in every fifth patients without clinical consequences during the short observation period.